Bio

Research:
(1) Working on the integrative analysis of regulatory elements for the modENCODE project Fly group.
(2) The cis-/trans- acting regulation in multiple species of fly and fly hybrids.

Bio

My research involves utilizing a combination of genomics, systems-biochemical, statistical, and computational approaches to study the role genetic variation plays in regulating transcription factor protein levels in the HapMap Yoruba population and growth factor-mediated signaling networks in breast cancer.

Bio

Dr. O’Brien joined the IGSB in February 2010.  She is interested in a range of belowground processes related to soil organic matter (SOM) cycling in a changing climate.  Her Ph.D. research was jointly advised by Miquel Gonzalez-Meler (University of Illinois at Chicago) and Julie Jastrow (Argonne National Laboratory), and focused on mechanistic controls on the rate and duration of SOM accumulation in restored perennial grasslands, especially the physical and chemical protection mechanisms that stabilize SOM.  Her postdoctoral research will expand on that theme by exploring the microbial processes that underpin the SOM dynamics observed over the landscape.  She will combine lab and field studies with next-generation molecular methods to link microbial community structure and function to SOM dynamics and the global carbon cycle.

Bio

Aaron Garoutte earned a BS in Biology at Hope College where he worked in a lab studying pioneer plant demography in Monte Verde Costa Rica.  He also worked on isolating fungicidal compounds present in the seeds of some pioneer plants using HPLC, column chromatography and bioassays.  After college he worked for an ecological consulting firm where he participated in various field surveys including wetland delineations, phase 1 site assessments and habitat restoration planning. Aaron also worked for JohnsonDiversey where he worked as a formulation chemist prior to joining the Antonopoulos Lab at Argonne in November 2008.  He has been working on developing metatranscriptome libraries from soil systems in addition to performing a variety of microbial ecological analyses of soils.

Bio

Dr. Brulc joined IGSB in August 2009.  Her Ph.D. research was advised by Dr. Bryan A. White (University of Illinois Urbana-Champaign) and focused on the divergence of complex microbial communities and their resulting community interactions on host nutrition and diet adaptation in mammalian gastrointestinal tracts, as it relates to efficient fiber degradation, using second-generation DNA sequencing technologies.  Her postdoctoral work will expand on utilizing bioinformatics and newly developed genomics technologies to observe the microbial impact on human gastrointestinal disease states and also assessing metabolic potential differentiation and microbial influence on ecosystem development in topsoil environments.

Bio

Brandon Bates received a BS in Biology: Genetics and Biotechnology from the University of Iowa. While attending Iowa as an undergraduate, he worked in the Cardiology Research Division at the University of Iowa Hospitals and Clinics. After receiving his degree, he remained with the University of Iowa Hospitals and Clinics, working as a Research Technician and Laboratory Manager with Dr. Peter J Mohler’s laboratory. During this time he contributed to Cardiology and Diabetes research, gaining experience in protein purification, tissue culture, confocal microscopy, and general molecular and microbial biology techniques. Brandon joined the Antonopoulos Lab at Argonne in October 2008. His research has consisted of preparing 16S rRNA tag sequence amplicon libraries from a variety of environmental samples for sequencing using second generation DNA sequencing technologies.

Bio

As a staff programmer in the White Lab, Jason’s primary interests involve supporting high-throughput sequencing projects with a focus on variation detection.  In addition, he is gaining experience in pipeline abstraction for the purpose of integration into a cloud-computing infrastructure.

In his spare time, Jason enjoys home-brewing, cooking, and motorcycling.

Bio

Dr. Roy Weiss is an expert in diseases of the thyroid and pituitary disorders—such as Cushing’s disease. Dr. Weiss has described several genetic diseases of the thyroid along with Dr. Samuel Refetoff. Together, they have one of the largest referral centers for genetic thyroid disease in the world. He also has one of the largest programs in the Midwest in the diagnosis and treatment of Cushing’s disease.

His research centers on the mechanisms of thyroid hormone action at the molecular, physiological, and psychological levels. Dr. Weiss has examined the molecular basis for the syndrome of resistance to thyroid hormone (RTH). He also has several clinical studies evaluating treatment of thyroid disease. Dr. Weiss’s research is supported by funds from the National Institutes of Health (NIH).

In addition to teaching medical student courses in physiology and pathology, Dr. Weiss currently holds a K24 award from the NIH to mentor fellows in clinical research.

He has been an invited speaker at national and international conferences. Dr. Weiss serves as associate editor of Thyroid and on the editorial board of the American Journal of Physiology. He has published more than 110 peer-reviewed articles on thyroid disease research and endocrinology.

Bio

John M. Cunningham, MD, is an internationally known expert in the treatment and research of childhood cancers and blood diseases. He has particular expertise in treating hemoglobinopathies, which are disorders that affect red blood cells, such as sickle cell disease and thalassemia. He is a recognized leader in the field of pediatric stem cell transplantation, and has developed novel uses for this life-saving treatment.

Research

Dr. White is a pioneer in combining experimental and computational techniques to understand the networks of factors that control biological systems during development and evolution. He has developed novel integrated systems biology approaches for studying complex diseases and identifying new diagnostic biomarkers for a variety of cancer types.  The White lab have particular focus on building genome-wide models of transcriptional networks, and we use an integrated approach that makes use of gene expression microarrays, large-scale protein-protein and protein-DNA interaction analyses, systematic RNAi analysis and high throughput polymorphism detection. By applying our methods to both closely and distantly related species, we are investigating how conserved molecular networks control basic developmental processes and how variation in molecular networks translates into variation in organismal phenotypes. We are particularly interested in the transcriptional networks controlled by nuclear receptor proteins in development and disease. We also are studying the transcriptional mechanisms involved in patterning early embryos. We make use of the compact Drosophila genome and the genomes of related species as model systems for many of our studies, and recently we have also begun to apply these genomics and computational approaches to investigations of the human genome.

Bio

The GS-FLX (454 Genome Sequencer) is run by Areej Ammar. Areej has a Bachelor of Science in Biochemistry from the University of Illinois at Chicago. Her previous lab experience was at the Department of Pharmacology, University of Illinois at Chicago where she worked on formyl peptide receptor signaling using various molecular biology techniques.

Bio

Illumina Genome Analyzer sequencing runs at HGAC are managed by Erin Dybdahl. Erin has a Bachelor’s in Bacteriology from the University of Wisconsin, Madison. Erin spent 3 years at Madison developing a knockout gene for Brucella melitensis to stop their ability to survive in acidic environments. She analyzed Brucella gene expression using microarray. At the University of Wisconsin, Milwaukee, Erin discovered a novel gene in zebrafish using in situ hybridization to study axon development in embryos.

Bio

Microarray processing is performed by technician, Tifani Eshoo. Tifani earned her B.S. in Biochemistry at the University of Wisconsin-Madison where she worked in a plant genetics lab investigating the epigenetic mechanisms that control flowering time in A. thaliana under Dr. Rick Amasino. Before joining the IGSB she worked with Dr. Michael Axtell at Pennsylvania State University where she helped devise a novel experimental method referred to as degradome sequencing, utilizing the Solexa-Illumina sequencing platform. This was the first experimental method to sequence miRNA- mediated cleavage products on a high-throughput scale, providing empirical evidence for confirmation of computationally predicted miRNA targets as well as in vivo miRNA functionality in plant species.

Research

I am interested in transcriptional regulatory networks, and applications of next generation sequencing technology.

Research

I. Molecular genetics of species differentiation - The main interest is in the genetic and molecular basis of species differences. (You can think of human vs. chimpanzee, if you wish. How many genetic differences delineate us from them?) We use sibling species of Drosophila to get to the answers (see Wu, C.-I and C.-T. Ting 2004 Genes and speciation. Nature Review Genetics 5: 114-122). Among the traits of special interest are hybrid incompatibility and sexual behavior divergence. These traits are what define species.

Current approaches
In the past, we took a gene-by-gene approach and have successfully cloned two speciation genes (see the list below, or Wu and Ting 2004). In the beginning of this new century, there is a need and an opportunity to take a system-wide approach in order to identify the majority of genes involved in a particular process of speciation. We shall study the divergence in mating behaviors between the Z (for Zimbabwe) and M (cosmopolitan) behavioral races of Drosophila melanogaster (Wu et al. 1995; Hollocher et al. 1997a, b; Ting et al. 2001). These two races are at the very nascent stage of species formation.

We wish to understand the genetic and transcriptional bases of phenotypic divergence at this early stage of speciation. As shown in the figure above, the studies will be at 3 different levels - genotype, transcriptome and phenotype. The scope will be genomic and the tools will include genotyping tiling array, expression microarrays, large-scale sequencing, behavioral QTL mapping and, finally, precise gene replacement.

Aim 1 – At the genotypic level, we will identify nucleotide sites that are strongly differentiated between the Z and M races in a whole-genome scan of expressed genes. These race-differentiating sites will anchor genetic mapping of transcription and phenotypic divergence. We will construct multiply recombined (MR) lines between the Z- and M-races for such mapping.

Aim 2 – At the transcriptional level, we shall study the expression profiles of the MR lines (in heads and reproductive organs of the two sexes) and correlate these profiles with their underlying genotypes. The regulation of transcription is important in linking phenotype and genotype.

Aim 3 – At the phenotypic level, we shall first attempt to find the transcriptional basis of the phenotypic divergence (behavioral isolation), using the MR lines. We shall also link phenotypic divergence to genotypic changes directly. Genotyping will be done by whole-genome tiling array. We expect to identify most candidate “speciation genes” between the Z- and M- races and will carry out precise gene replacement (Rong and Golic 2000; Greenberg et al. 2003; Sun et al. 2004) to confirm their effects on the mating behavior.

II. Genomics and population genetics -The torrent of genomic data by DNA sequencing and expression microarrays have provided unprecedented opportunities for analyzing natural selection and adaptation. Speciation is the consequence of natural selection driving populations to adapt to different environments. It is also a genome-scale phenomenon.

Current approaches -We continue to carry out data analysis as done in the papers cited below. The data were often obtained from the public domain and we have been developing theoretical tools to analyze these data. At the same time, we also carry out large-scale data collection in collaboration with various sequencing centers in several countries. An example is our organization of an international consortium that sequenced 10,000 full-length transcripts from the macaque brain and testis (see Wang et al. in review). This effort will be the foundation of a comparative primate genome database. We also collaborate with these centers on many other fronts (see He et al. 2004 and Song et al. 2005 for the analysis of SARS evolution).

Bio

Rick Stevens is interested in the development of innovative tools and techniques that enable computational scientists to solve large-scale problems more effectively on the most advanced high-performance computers.

Research

Rick Stevens is associate laboratory director for Computing, Environment, and Life Sciences. He heads Argonne’s advanced computing initiative targeting the development of exascale computing technology and systems and computational biology. He is also a professor of computer science at the University of Chicago and is senior fellow of the Argonne/University of Chicago Computation Institute, a multidisciplinary institute aimed at connecting computing to all areas of inquiry at the University and the Laboratory. In addition, he is co-Director of the Argonne Futures Lab, a research group he started in 1994 to investigate problems in large-scale scientific visualization and advanced collaboration environments (his group in the Futures Lab has developed the widely deployed Access Grid collaboration system.

Prof. Stevens is interested in the development of innovative tools and techniques that enable computational scientists to solve important large-scale problems effectively on advanced scientific computers. Specifically, his research focuses on three principal areas: advanced collaboration and visualization environments, high-performance computer architectures, and computational problems in the life sciences, most recently in systems biology. In addition to his research work, Prof. Stevens teaches courses on computer architecture, collaboration technology, virtual reality, parallel computing, wireless sensors networks, and computational science.

Research

Computational biology and bioinformatics, text mining in biomedical domain, and applications of computational approaches in drug discovery

Research

I am currently working on two projects. First, to complement the antibody production of the ModENCODE project, we are tagging Drosophila transcription factors with eGFP in ~20 kb BACs in the P[acman] vector. We are in the process of characterizing the expression patterns and functionality of these tagged constructs through anti-GFP staining of embryos and third-instar tissues and rescue experiments in lethal mutant backgrounds. We will follow this up with ChIP-Chip experiments with an anti-GFP antibody against the tagged protein to determine the DNA binding locations of these transcription factors. Ultimately, this procedure will be used to fill in any remaining gaps in the ModENCODE data set due to difficulty producing antibodies against certain transcription factors.

Second, I am looking at the genome wide transcriptional response to the juvenile hormone mimic methoprene in Drosophila cell culture and whole animals using microarrays.

Research

My general interests include Bayesian and computational statistics, particularly when applied to problems in population genetics. Specific interests include:

* estimating haplotypes from population genotype data (for which I distribute a software package PHASE).
* developing statistical models for patterns of linkage disequilibrium across multiple loci, and using these patterns to identify recombination hotspots.
* spatial modelling of allele frequency variation.

Research

Dr. Solway’s laboratory addresses molecular mechanisms underlying airway constrictor hyperresponsiveness in asthma, including:
1) Regulation of smooth muscle gene expression (with focus on SRF and GATA5);
2) Evaluation of mutations and mechanisms underlying heritable cholinergic hyperresponsiveness in a kindred of ENU-mutagenized mice;
3) Functional genetics of asthma, (consequences of genetic variations and transcriptional analysis of endobronchial biopsies);
4) Molecular mechanisms that regulate the mechanical plasticity-elasticity (taffy-like vs. rubber band-like) balance in contracted airway smooth muscle.  

Research

We focus on integrating technologies to sustainably produce biofuels and biobased products. The goal is to design fermentation and enzymatic conversion systems that will facilitate continuous product recovery. Currently we work on organic acids and alcohols. Recent work has
focused on:
* Anaerobic bacteria that utilize C1 compounds (H2, CO, and CO2)
* Enzyme and cell supported systems for biocatalyst stability and product separations
* Restricting nutrient requirements in fermentations

Other areas of interest are
* Metabolic engineering for novel biobased products
* Increased productivity in methanogenic communities

The team brings together unique capabilities from microbiology through chemical engineering to address these issues.

Bio

He researches the evolutionary origin of anatomical features of animals. His most recent discovery,  Tiktaalik roseae, has been dubbed the “missing link” between fish and land animals.

Research

I seek to understand the mechanisms behind the evolutionary origin of new anatomical features and faunas. The philosophy that underlies all of my empirical work is derived from the conviction that progress in the study of evolutionary biology results from linking research across diverse temporal, phylogenetic, and structural scales. The Origin of Novel Faunas and Anatomical Systems: Much of today’s vertebrate diversity was defined by ecological and evolutionary shifts that happened during two critical intervals in the history of the Earth: the Devonian and the Triassic. These periods serve as the focal point for my research because they witness the origin of both new ecosystems and new anatomical designs. My expeditionary research supplies new fossils and a paleoenvironmental context to understand the origin of faunas, whereas our morphological, functional, and developmental studies yield hypotheses on anatomical transformations.

Over the past fifteen years, I have developed expeditionary research programs in Canada, Africa, the continental United States, Asia, and Greenland. These expeditions have led to new insights on the origin of major groups of vertebrates (mammals, frogs, crocodiles, tetrapods, and sarcopterygian fish). Future studies on the origins of pterosaurs, rhizodontid fish, dinosaurs, and salamanders will rely heavily on fossils discovered over the past five years. Examples include the newly discovered adult fin and juvenile skeleton of the fish, Sauripterus. These fossils are providing evidence on the ways that appendage function and skeletal development shifted during the evolutionary radiation of lobe-finned fish. Indeed, this evolutionary radiation is temporally linked to the origin of new freshwater environments. Consequently, the analysis of Sauripterus will place comparative studies of fin structure, development and function in a phylogenetic and paleoenvironmental context.

The goals of the paleontological research dovetail with those of my neontological studies. New fossils, such as Sauripterus, offer tests of hypotheses that derive from our comparative analysis of genetic and morphogenetic processes. For example, the comparison of developmental pathways common to the appendages of all animals suggests genetic mechanisms for parallel evolution and homology. Regularities of variation may reflect the fact that similar regulatory genes are used in the developmental patterning of diverse types of animals.

The Origin of Morphological Variation: The ~400 million year history of terrestrial animals reveals surprising patterns of anatomical stasis and parallel evolution: similar designs crop up in different species living in different environments. Salamanders, for example, arose over 150 million years ago, but have retained a very stable body plan in the face of environmental change and genetic variation. The study of these regularities transcends ecological and paleontological timescales because explanations of larger-scale patterns can be sought in the mechanisms that structure anatomical variation in populations today. Accordingly, my research has involved collecting data on intraspecific variation from diverse populations, developing predictive models of variation based on ontogeny, and comparing developmental processes in diverse salamanders that live in different environmental settings.

Salamander limbs are a model system to approach these issues because of the diversity of their developmental systems and life histories. In addition, the widespread occurrence of parallelism provides us with a window to develop predictive rules about the origin of variation in populations. Over the past seven years, colleagues and I have composed a database of limb variation and ontogeny in populations of diverse salamanders. Virtually all of the species analyzed to date possess variant conditions that both restore ancient features and anticipate more derived conditions seen in distantly-related species. Much of the observed intraspecific variation is predictable from a knowledge of phylogenetic history or development. Ultimately, if these historical and developmental effects resulted in long-term evolutionary patterns, they must have acted over geological timescales. Tests of this hypothesis will come from the study of the Chinese Cretaceous where, in collaboration with colleagues, I am studying variation of salamanders in a Cretaceous pond that were killed in a single mass-mortality event.

Phylogenetic analysis of ontogenetic trajectories in salamanders affords critical assessments of the role of historical, ecological, and structural factors in evolution. Analysis of development in salamanders with different life histories suggests certain aspects of early limb development are highly sensitive to variation in larval biology. I intend to explore this link between ontogenetic diversity and anatomical variation in the future by using experimental and comparative studies of ontogeny.

Research

Our research is motivated by two fundamental issues in developmental and molecular biology (i) how do regulatory networks of transcription factors specify the generation of distinct cell fates from stem cells and (ii) what kinds of molecular mechanisms are used to orchestrate lineage and stage-specific patterns of gene activity during cellular differentiation. The laboratory has focused our work in the hematopoietic system with particular emphasis on analyzing the development of various lineages of the immune system. The hematopoietic system is a leading developmental model for exploring the nature of the regulatory circuitry that enables a self-renewing pluripotent stem cell (HSC) to generate a complex set of differentiated cell types including erythrocytes, megakaryocytes, macrophages, granulocytes and B and T lymphocytes. We are interested in developing approaches for the directed and efficient generation of specific immune cells from embryonic stem cells. To explore molecular mechanisms that control cell type specific patterns of gene activity, we focus on immunoglobulin (Ig) gene loci in B lymphocytes because of their central role in development, distinctive structural organization and recombination dynamics.

Bio

Dr. Solomon is the IGSB Research Director who coordinates large-scale NIH grant submission, the Institute's administration and research core facilities, responsible for directing research activities for IGSB & the Chicago Center for Systems Biology (CCSB).

Research

Jonathan C. Silverstein, associate director of the Computation Institute of the University of Chicago and Argonne National Laboratory is associate professor of Surgery, Radiology, and The College, scientific director of the Chicago Biomedical Consortium, and president of the HealthGrid.US Alliance. He focuses on the integration of advanced computing and communication technologies into biomedicine, particularly applying Grid computing, and on the design, implementation, and evaluation of high-performance collaboration environments for anatomic education and surgery. He holds an M.D. from Washington University (St. Louis) and an M.S. from Harvard School of Public Health. He is a Fellow of the American College of Surgeons and a Fellow of the American College of Medical Informatics. Dr. Silverstein provides leadership in information technology initiatives intended to transform operations at the University of Chicago Medical Center and is informatics director for the University of Chicago’s Clinical and Translational Science Award (CTSA) program. He has served on various national advisory panels and currently serves on the Board of Scientific Counselors for the Lister Hill Center of the NIH National Library of Medicine.

Research

Protein Synthesis of Drosophila Transcription factor fragments in E. coli.

Research

Our laboratory examines the mechanisms and strategies whereby pathogenic bacteria cause human disease. Several different microbes are being investigated.

The cell wall of Staphylococcus aureus and other Gram-positive pathogens can be viewed as a surface organelle with anchored proteins that interact with the host environment during infection. Our research has revealed four different mechanisms of protein anchoring to the cell wall envelope. Surface proteins bearing a C-terminal sorting signal with a LPXTG motif are cleaved by the sortase A enzyme and linked to the cell wall crossbridges of peptidoglycan. This group of surface proteins is essential for pathogenesis and mediates bacterial attachment to host tissues and escape from the immune system. Surface proteins bearing a C-terminal sorting signal with a NPQTN motif are cleaved by sortase B. This mechanism is involved in iron transport during infection and is required for bacterial persistence in the host. Autolysins are enzymes that cleave the cell wall envelope at defined sites. One group of autolysins, e.g. lysostaphin and f11 hydrolase, is targeted to a receptor that is distributed uniformly over the bacterial surface. Another autolysins is targeted to the equatorial surface rings of staphylococci and mediates peptidoglycan cleavage at cell divisions sites. Our laboratory entertains genetic, molecular biological, biochemical, microscopic as well as animal infectious strategies to reveal mechanisms of protein targeting and the role in the establishment of disease. Our results are useful for the design of new therapies that can be used for the treatment of human infections caused by S. aureus and other Gram-positive bacteria.

Pathogenic Yersinia spp. invade their human hosts and colonize lymphoid tissues. This unique infectious strategy requires bacterial mechanisms of immune evasion. Yersinia type III secretion prevents the phagocytic killing of bacteria during infection. Further, the type III machinery intoxicates and kills immune cells, thereby impairing the host’s ability to clear invasive Yersinia. In fact, the pathogenesis of the most notorious of all pathogens, Yersinia pestis - the causative agent of plague, relies on the type III secretion machinery. We are interested in the mechanisms of protein recognition and transport by the type III machinery. Our results suggest that mRNAs of Yops, the substrates of the type III machinery, harbor signals that lead to the secretion of the encoded polypeptide chains. Current work is mapping the secretion signals and analyzing the mode of mRNA recognition by the type III machinery. A second area of research is the regulation of the type III secretion machinery. Upon bacterial entry into the host, Yersinia sense three environmental signals: a temperature shift to 37 ºC, glutamate ions as well as serum proteins. These signals trigger yersiniae to express and assemble the type III machinery and to transport YopB, YopD, YopR and LcrV into the extra-cellular milieu. Docking of yersiniae on the surface of immune cells leads to the insertion of type III secretion machinery needles into the plasma membrane of host cells and in sensing of the low calcium concentration of the cell’s interior. Yersinia respond to the low calcium signal by transporting YopE, YopH, YopM, YopN, YopO, YopP, YopT and YscM (LcrQ) into the cytosol of host cells. The sum of the function of these toxic proteins leads to a block in phagocytosis and in the killing of macrophages. Research on type III secretion represents a hotly contested frontier of microbiological science. Our results will be useful for the treatment of human infections caused by Yersinia, including the biological warfare agent Yersinia pestis, as well as several other Gram-negative pathogens.

Research

Daniel S. Schabacker received his PhD in Immunology / Protein Biochemistry at the University of Illinois, Urbana-Champaign. As Team Leader of the Biochip Group he is the lead scientist for the development of the Argonne National Laboratory biochip portfolio. In this role he is leading the development of nucleic acid and protein array applications. Working with both commercial licensees of the technology and governmental sponsors he coordinates product development of biochips and attendant hardware. Current research includes the development of, 1) a point-of-care human diagnostic respiratory biochip capable of rapidly identifying both bacterial and viral pathogens, 2) Veterinary diagnostic biochips capable of identifying causative organism(s) as well as antibiotic resistance for bovine respiratory syndrome and bovine mastitis, 3) Threat agent detection systems for rapid analysis (<15 minutes sample-to-answer) of multiple targets providing diagnostic confidence level outputs, and 4) Biochips and systems for biomarker discovery.

Research

The Proteomics and Informatics Services Facility provides investigators affiliated with CBC member institutions access to a number of mass spectrometers optimized for use in proteomics studies. The facility operates by syndicating the responsibility for the provision, operation and maintenance of these mass spectrometers to the RRC’s Mass Spectrometry Laboratory (MSL) and by syndicating sample preparation and fractionation activities to the RRC Protein Laboratory (PL). Scientists from these laboratories work together in conjunction with informatics specialists directly employed by the Proteomics facility to provide investigators with a range of services utilizing the combined capabilities of these laboratories.

Scientists employed and affiliated with the PSF can design and conduct experimental protocols, reduce and interpret data and provide pre-experimental consultation to investigators who seek to incorporate proteomic experimental strategies into their research programs. Researchers may submit samples to the facility for protein separation, post separation processing, mass spectroscopy and data analysis. Alternatively, qualified users may schedule instrument time to analyze their own samples. Two BioWorks workstations and one with Mascot and additional proteomics software may be scheduled for use. Please follow the links on the left for an online order page, scheduling various instruments, and a resource page to help you with protein purification.
The PSF also maintains close ties with investigators at UIC and other CBC member institutions (University of Chicago and Northwestern University) who specialize in Mass Spectrometry and Informatics research in order to provide opportunities for advanced collaboration, research referrals and protocol development.

The Proteomics and Informatics Services Facility was established by a grant from The Searle Funds at The Chicago Community Trust to the Chicago Biomedical Consortium.

Research

I am broadly interested in the evolution of development (Evo-Devo), evolutionary genomics and molecular evolution. The goal of the lab is to integrate developmental, genomic and computational approaches to understand the evolution of genes and gene functions. Currently we are pursuing two major projects:

1. The origin and diversification of the nervous system

The origin of multicellular animals was accompanied by an increase in the number of distinct cell types, chief among these being neurons. How and when did neurons arise in evolution? We are aiming to reconstruct the series of molecular events that led to their origin and subsequent diversification.

We are asking - What genes are expressed in all neurons, and no cells other than neurons? Such pan-neuronal genes comprise a molecular definition of basic neuronal features and thus provide a window into their origin. By using computational genomics we have discovered that many pan-neuronal genes in C. elegans share common motifs in their cis-regulatory elements, suggesting that their expression is controlled by a common set of transcription factors. We are currently combining experimentation with computational analyses of the C. elegans and other animal genomes to identify sets of genes that characterize different neuronal subtypes and will use these to elucidate the evolution of the animal nervous systems.

2. Evolution of transcriptional gene regulation

Although it is thought that morphological differences between species are largely caused by changes in regulatory DNA sequences, relatively little is known about their evolution. We are working to fill this gap by investigating the pattern and functional consequences of cis- and trans-regulatory evolution.

Research

My project involves investigation of the tissue specificity of nuclear hormone receptor activity in endometrial and breast cancer cells. I use expression profiling, ChIP-chip, qRT-PCR RNAi and Reporter assays to identify transcriptional differences and cofactor requirements for tissue specific hormone responses in the cells.

Research

Dr. Russell’s scientific training, background, experience, and productivity encompass a range of disciplines and forge linkages in the continuum between quantitative biology, bioengineering and physiology. Her current NIH support funds two collaborative projects, one on heart failure for regulation of protein synthesis and remodeling of cell shape, and the other on development of a novel cell culture system using bioengineering and surface chemistry modification. Many of her studies have been done in close collaboration with clinicians (muscular dystrophies, urinary incontinence, heart failure).

Research

I am a statistical physicist by training. At IGSB, I collaborate with experimentally-minded colleagues to design mathematical models for analyzing experimental data. Towards this end, we aim to utilize various methods used for modeling complex systems and techniques of probabilistic calculus.

Research

Cancer is characterized by loss of normal cellular growth control. Intracellular signal transduction pathways are critical to the proper interpretation and integration of growth regulatory stimuli, and intricate mechanisms have evolved for ensuring the fidelity of cell replication. Small changes that alter the magnitude of these signals can significantly impact cellular outcomes. Thus, elucidating the nature of these signaling pathways and how they are modulated is central to understanding cell cycle control and the maintenance of genomic integrity. The focus of our laboratory is to determine the critical mechanisms that regulate cell growth and differentiation in response to growth factor or oncogenic stimulation and identify key targets for therapeutic intervention.

Research

My laboratory works at the interface between signal transduction and developmental biology. The long term goal of our research is to understand how complex developmental decisions are controlled in time and space by multiple signaling pathways. Our approach involves first identifying the individual genes comprising the regulatory network, and second elucidating the complex functional relationships between the components in order to determine the critical nodes where information is integrated. Specifically, we study how nuclear events downstream of the receptor tyrosine kinase (RTK) pathway regulate cell fate specification decisions during embryonic and retinal neural development, with particular emphasis on elucidating the post-translational control mechanisms that modulate and facilitate interactions within the network. Drosophila, and in particular the fly eye, provides an unparalleled model tissue in which to study the mechanisms of signal integration both because of its experimental tractability and because a complex interplay between multiple signaling pathways regulates many aspects of its development. Furthermore, because developmental signaling mechanisms have all been highly conserved in evolution, our work elucidating the molecular circuitries used in Drosophila directly advances understanding of how cell fates are designated and maintained in all animals, and why misregulation results in cancer and disease in humans. Thus our current and long term strategy involves combining genetic, genomic, proteomic, biochemical and cell biological methodologies in order to elucidate the conserved molecular circuitries that link and coordinate signaling modules in the developing retina.

Research

Our interest is in understanding how different evolutionary forces have shaped patterns of genetic variation in humans, and conversely, in learning about recombination, demography and selection from patterns of genetic variation observed in samples of extant humans. Our research combines modeling, the development of statistical tools and data analysis. The lab is “dry”, although we often collaborate closely with experimentalists.

Bio

Blum Riese Distinguished Service Professor of Medicine, Molecular Genetics & Cell Biology and Human Genetics. Dr. Janet Rowley is a pioneer in demonstrating that cancer is a genetic disease. Her work established that cancer is a genetic disease. She demonstrated that mutations in critical genes lead to specific forms of leukemia and lymphoma, and that one can determine the form of cancer present in a patient directly from the cancer’s genes. This changed the way cancer was understood, opened the door to development of drugs directed at the cancer-specific genetic abnormalities and created the paradigm that still drives cancer research.

Research

My laboratory is analyzing the genetic consequences of the recurring chromosome abnormalities seen in human leukemia cells. We have cloned several new genes at translocation breakpoints and are investigating how the chromosome rearrangements alter the structure of the genes and how this in turn alters the structure and function of the proteins. Many of the genes at these breakpoints are transcription factors, and thus the identification of the genes regulated by these proteins will be important. In addition, we are also mapping the region of chromsome deletions to identify the involved genes; these will most likely be tumor suppressor genes. These studies are carried out using not only molecular genetic techniques but also chromosome microdissection and fluorescence in situ hybridization of the appropriate probes to normal metaphase chromosomes and interphase cells as well as to cells from leukemia patients treated at the University of Chicago Medical Center.

Research

My research group tackles the following questions. What is the nature and extent of genetic variation within and between human populations? What are the biological and evolutionary processes that have produced the observed patterns of variation? How do genotypes contribute to phenotypes for complex traits (and how can we identify the relevant genetic variants)?

In our work, we develop new statistical methods for genetic analysis and also analyze data from humans and other organisms. Much of our statistical work makes use of computationally intensive approaches such as Markov chain Monte Carlo; these approaches can be effective for extracting subtle signals from large and complex data sets. In general, we aim to tackle problems where careful analysis, usually from a population genetic perspective, seems likely to yield new biological insights.

The scope of our past and ongoing research includes work in four main areas: (i) methods for gene mapping of complex traits; (ii) inference of population structure from genetic data; (iii) history and structure of human populations; and (iv) genome variation and evolution. We also distribute a number of programs and software packages, including the popular package structure for inferring population structure from genetic data [“Software” link above].

We are based in the Department of Human Genetics at the University of Chicago. Both our department, and the university in general, are very strong in population genetics, complex traits, and evolutionary biology. In particular we enjoy close ties with the labs led by Molly Przeworski, Matthew Stephens, Anna Di Rienzo, Nancy Cox and Carole Ober.

Research

My research interests include the evolution of gene transcription in a developmental context.

Bio

Ms. Nicolette Pavlovics is an exceptional recent graduate. Her biology and technology skills enable her to provide additional support for screening projects.

Research

I perform tissue culture and analysis of proteins, RNA and DNA for the Nuclear Receptor project. I am also responsible for lab safety.

Research

My lab studies the genetic basis of cancer susceptibility. Genetically, we are all very similar, but not identical. Some of this normal variation is insignificant, but some may have important functional consequences. Our goal is to discover the critical sources of functional heterogeneity in the pathways that are the barriers against the cellular transition from normal to cancer. We hope that these:

1. Will be clinically useful as biomakers of cancer risk by which cancer prevention
strategies can be indivualized based on each person’s unique genetic endowment.
2. Will point towards noveltargets for new rationally designed molecular
chemotherapeutics that short circuit abmormal pathways in cancer cells while
sparing cancer patients the toxicities of currently used treatments.
Cancer results from a mutation or a series of mutations that cause a cell to escape from normal regulatory controls. Cellular stresses such as DNA damage vastly increase the rate of mutation, and therefore, the likelihood of malignant transformation. Apoptosis, or programmed cell death, is the primary cellular defense against the oncogenic potential of these stresses, and so, our research has been focused upon understanding the genetics of apoptosis.

The p53 tumor suppressor is the central mediator of apoptosis. It is induced and activated by a variety of stresses, and thereupon initiates transcriptional response programs that result in apoptosis. Underscoring the importance of p53 is the observation that it is mutated in half of all cases of cancer. As would be predicted, concomitant defects in apoptosis are, in fact, a hallmark of cancer. If loss of p53 is so important for cancer, it is a paradox that p53 is almost never mutated in the most common pediatric cancer, acute lymphoblastic leukemia (ALL). This led us to hypothesize that even within the spectrum of normal, genetic variation results in heterogeneity in the p53-mediated apoptotic stress response. We found that susceptibility to DNA damage-induced apoptosis is a genetically determined program that is completely reproducible for a given individual, but which varies significantly among individuals. We have also identified several polymorphic variants within the p53 pathway that both alter the p53-mediated apoptotic response to stress, and which are associated with increased cancer risk.

We are now searching for other sources of genetic variation � both intrinsic to the p53 pathway and extrinsic to the p53 pathway—that alter susceptibility to damage-induced apoptosis, and which may be biomarkers for cancer susceptibility, or targets for new cancer therapies. Towards this end, we have four major projects ongoing utilizing both genome-wide and candidate gene approaches.

1. The identification of the genetic determinants of apoptosis:
Using about 400 cell lines from over 30 well-characterized multigenerational pedigrees, we are employing an unbiased genome-wide strategy to map by linkage analysis the genomic loci that contain the critical genetic determinants of DNA damage-induced apoptosis. As the polymorphic sequence variants identified by this study modulate the efficiency of the apoptotic response to oncogenic stress in different individuals, they are likely to translate into clinical tests by which cancer risk can be assessed and quantified.

2. The identification of the p53 network of apoptosis:
Although a number of p53 target genes have been identified, it remains unclear how p53 regulates apoptosis. We are using a genetic approach and expression microarray analysis to identify and model the p53-dependent transcriptional network of apoptosis. Identified p53 target genes will be attractive candidates for extensive resequencing to identify functional SNPs that may be clinically significant markers of disease risk. They may also be exciting novel targets for new therapeutics.

3. The identification of novel biomarkers and therapeutic targets in pediatric leukemia:
By array-based comparative genomic hybridization, we are mapping genomic regions amplified or deleted in pediatric ALL and comparing these to genomic loci commonly amplified or deleted in adult onset ALL. correlating this with a powerful predictor of outcome, the Day 7 bone marrow analysis. These regions will very likely contain oncogenes or tumor suppressors that are under selective pressure in ALL, and which may be biomarkers predictive of outcome, or novel therapeutic targets.

4. The identification of genomic susceptibility loci in secondary leukemia:
Using both genome-wide and candidate gene approaches, we are mapping susceptibility loci for secondary AML in a large and well-characterized cohort of patients. Because these patients develop leukemia following prior treatment with DNA-damaging agents, the identification of the genetic determinants of susceptibility may lead to insights into the critical genes and pathways by which cells generally respond to mutagens and other carcinogenic stresses, and thereby prevent oncogenesis. In addition, clinically, if cancer survivors at the greatest risk for the development of t-AML can be identified at the time of their initial diagnosis, then it may be possible to alter their chemotherapeutic regimen to reflect this risk, and thereby protect them from this devastating condition.

Research

tRNA is essential for protein synthesis and life. Genomes contain hundreds of tRNA genes. Translational regulation is related to the dynamic properties of tRNA that constantly change to facilitate stress response and cellular adaptation to new environments and to control gene expression in differentiated organisms. We developed microarray methods that measure tRNA abundance, its fraction of aminoacylation and misacylation at the genomic scale. We are exploring roles of tRNA in translational control in yeast and in mammalian cells including cancer. Over 100 types of post-transcriptional modifications have been identified in thousands of RNA sites from bacteria to man. They include methylation of bases and the ribose backbone, rotation and reduction of uridine, base deamination, elaborate addition of ring structures and carbohydrate moieties, and so on. RNA modification enzymes represent 1-2% of all genes in bacteria. Hundreds of guide RNAs and dozens of proteins are used to direct modifications in eukaryotic rRNAs. RNA modifications are involved in stress response, environmental adaptation, antibiotic resistance and human neurology. We developed genomic methods that detect and quantify changes in modification fraction. We are applying these high throughput methods to study the function of RNA modifications at the genomic level during cell growth, adaptation and development. Non-coding RNAs perform biological function without being translated into proteins. Some estimates suggest that in human, the number of non-coding RNAs may be comparable to the number of coding RNAs. We are working on methods for folding studies of non-coding RNAs, and for structural determination using cryo-Electron Microscopy. Folding during transcription is also studied to understand non-coding RNA folding in the cell..  

Research

The major research objectives of my laboratory are to identify genes that influence complex phenotypes, to understand their evolutionary history, and to elucidate how variation in these genes influences function. Our laboratory focuses on phenotypes related to fertility and to common diseases, and are conducted in a founder population, the Hutterites, and in outbred patient populations.

Our studies of fertility have focused primarily on HLA-region genes, including the non-classical HLA-G gene and the olfactory receptor genes in the extended class I region. These studies have indicated that genes in different HLA regions influence different components of fertility. For example, maternal-fetal compatibility for alleles at the class II locus, HLA-DRB1, is associated with reduced fecundity, maternal-fetal compatibility for alleles at the class I locus, HLA-B, is associated with sporadic fetal loss, while specific variants in the promoter and coding region of HLA-G are associated with both sporadic and recurrent pregnancy loss. We have recently completed a genome-wide screen for non-HLA loci that influence fecundity in the Hutterites and are initiating fine mapping and positionally cloning studies in selected regions.

Our studies of common diseases focus mainly on phenotypes that are associated with asthma and heart disease. In collaboration with Mary Sara McPeek and Mark Abney, we developed novel methods for quantitative trait locus (QTL) mapping in the Hutterites, and have studied >25 quantitative traits that are associated with common diseases. Fine mapping and positional cloning studies are underway for some of these traits. In addition, we have identified three chromosomal regions that house asthma-susceptibility loci (on 5p, 6p, and 19q) that are currently the focus of positional cloning studies in our laboratory in both the Hutterites and families ascertained as part of the Collaborative Study on the Genetics of Asthma (CSGA). Lastly, we collaborate with investigators at the University of Wisconsin – Madison on the Childhood Origins of ASThma (COAST) Study. This is a prospective cohort study of children at high risk for developing asthma and allergy, who are followed from birth onward. Our laboratory is genotyping the children in this study and their parents to identify genetic variation that influences the development of the immune system in the first year of life and the subsequent development of asthma and atopic disease, as well as variation that interacts with early life environmental exposures to influence these phenotypes. We have recently identified variation at several candidate loci with direct effects on first year immune and atopic phenotypes, and that interact with daycare exposure in the first year of life to influence the developing immune system.

Research

My research interests are diverse and include: treatment of breast cancer, especially in young or pregnant women; familial cancers; molecular genetics of cancer; cancer risk assessment and chemoprevention; breast cancer and minority populations and disparities in health outcomes. My clinical interests include breast cancer, cancer risk assessment, cancer prevention, and general hematology and medical oncology.

Research

As part of the modENCODE project, I am mapping the position of transcription factors and DNA associated Proteins on the genome of the fruitfly Drosophila melanogaster. To do this I have led the development of a ChIP-chip pipeline in the lab. This pipeline comprises three different modules. In the first part, we are producing and validating ChIP-grade polyclonal antibodies for the fly Transcription Factors. These antibodies are then used in Chromatin Immuno-Precipitation (ChIP) experiments. The result of ChIP experiments is a library of DNA sequences enriched in binding sites for the protein of interest. To reveal the enriched fragments, we are hybridizing ChIP samples on genome-wide tiling microarrays. The third part of our pipeline is the development of automated bioinformatic tools for the analysis of microarrays and their integration into the public databases as well as the modENCODE repository.

Research

My main interest is in the area of evolution of gene regulation via genomic approaches.

Research

Our group is interested in dissecting the architecture and function of gene regulatory networks. We investigate how the multiple transcription activators, repressors, boundary elements connected to a gene interact and orchestrate the precise tissue-specific and temporal-specific expression pattern of that gene. Understanding this process is critical since it is thought that malfunction of the regulatory program of certain genes underlie the cause of several human diseases. We focus on heart development and congenital heart diseases as substrates to test our hypotheses, and we use mouse and zebrafish genetic engineering, comparative genomics, bioinformatics and other high throughput genomic screening and validation strategies as experimental tools.  

Research

Signal Transduction

Reversible ubiquitination and regulation of signaling: Protein ubiquitination can have many outcomes depending on the length of the ubiquitin chain and the type of linkage. The 2004 Nobel Prize in Chemistry was awarded for the elucidation of the ubiutin-proteasome pathway in which proteins tagged with Lys-48-linked ubiquitin chains greater than 3 in length (polyubiquitination) are targeted to the proteasome for degradation. By contrast, short chains of Lys-63-linked ubiquitin act to coordinate the endocytic machinery and the internal trafficking of endocytic vesicles. We are interested ubiquitination as a regulated and reversible process that creates docking sites for a range of ubiquitin-binding proteins. We are currently studying the role of various ubiqutin linkages in regulating signaling events from activated cell surface receptors (the EGF-R and the T-cell receptor), and the role of specific deubiquitinating enzymes in modulating cellular signal transduction.

Systems Biology/Bioinformatics

The SH2-ome: The SH2 domain (http://sh2.uchicago.edu/) is a modular protein interaction domain that selectively binds to phosphorylated tyrosine containing sequences, and in doing so functions as the critical link between tyrosine kinases and downstream signaling. As such, SH2 domain containing proteins play key role in signaling cascades implicated in a wide range of human diseases, including cancers, diabetes, autoimmune diseases and a wide range of bacterial and viral pathogens. We have recently completed an initial bioinformatic analysis of the human and mouse complement of SH2 domains (Molecular Cell). In doing so, we identified a number of previously unknown SH2 domain proteins. We are utilizing a combination of chemical, biochemical, and cell biology techniques to determine the binding preference and cellular role of these novel proteins. We are also conducting an evolutionary analysis of SH2 domains using a variety of techniques, including analysis of intron-exon boundary structure, domains-assisted sequence comparison, structural and functional analysis.

Proteoscape: With support from the Cancer Center, we are developing a large protein-centered relational database to act as both an investigational tool as well as an underlying support database for future biomedical informatics. The modular nature of proteins involved in signal transduction and cancer (see our review published in Science 2003) is allowing us to develop detailed approaches to bioinformatic analysis of a wide range of proteins involved in health and disease. The SH2 domain website is the best developed resource based upon the Proteoscape database.

Self-Assembly and Complexity

Ultrasensitivity: We are interested in how binding interactions that depend on a high-local concentration of low-affinity binding sites can act to set thresholds, integrate signals and create all-or-none responses on a single cell level. We have previously identified the requirement for multi-site phosphorylation of the CDK inhibitor Sic1 to allow a productive interaction with Cdc4 - an event that controls the initiation of DNA replication and the G1 to S-phase transition in the cell cycle (published in Nature, 2001). A project is available to study a variety of aspects of this fundamental problem using computational modeling, biophysical and biochemical techniques.  

Research

Our laboratory investigates the molecular basis of cardiac morphogenesis and Congenital Heart Disease. Congenital Heart Disease, or structural malformations of the heart present at birth, is the most common class of human birth defects. We employ forward and reverse genetic approaches in the mouse to address the genetic basis of structural heart disease. We use genetic, molecular, and biochemical methods to investigate the specific aspects of cardiac morphogenesis involved in Congenital Heart Disease.

We have initiated a gene discovery program using a forward genetic screen to identify mice with mutations affecting genes required for cardiac morphogenesis. We have established a screening strategy based on the fetal to neonatal circulatory transition. We find this strategy selects for cardiac morphogenesis defects commonly observed in human patients with Congenital Heart Disease. We have identified and mapped mutations resulting in an array of heart defects.

Our initial focus has been on defects of the cardiac valves. From our forward screen, we have mapped mutations from four lines with cardiac valve defects and have cloned one, in a gene implicated in sonic hedgehog signaling. We also employ reverse genetic approaches to investigate early aspects of cardiac valve development. Conditionally removing Smad4 from the endocardium, the primary valve cell set progenitor, results in an early failure of valve development. We are currently investigating the valve stem cell population.

The long-term objective of the work in our laboratory is to (1) Identify genes involved in the aspects of mammalian cardiac morphogenesis pertinent to human Congenital Heart Disease, (2) Understand the role of the identified gene products in cardiac morphogenesis, and (3) Gain a mechanistic understanding of how mutation in the identified genes results in cardiac morphogenetic defects and human Congenital Heart Disease.

Research

Understanding the principles underlying CELLULAR QUALITY CONTROL — the integration of processes by which the cell senses, responds and adapts to environmental and physiological challenges — is among the most fascinating problems in biology. The appearance of incorrectly expressed or improperly folded proteins results in a cellular stress response involving activation of stress-induced transcription factors and leads to the elevated expression of molecular chaperones and proteases that serve to clear damaged proteins.

An imbalance in protein homeostasis results in the accumulation of misfolded and aggregation-prone proteins that are poorly refolded and degraded, often accumulating as oligomeric intermediate species and aggregates in different subcellular compartments. These events are hallmarks of human genetic diseases including the polyglutamine-expansion diseases such as Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, familial ALS, prion diseases, amyloidosis, cystic fibrosis, and a-1-antitrypsin disease. This has led to increased interest in the toxicity and pathogenesis of misfolded proteins and the role of protein aggregates in cellular dysgenesis.

Our laboratory is interested in the fundamental events that underlie the appearance of misfolded proteins and their consequence to protein homeostasis, cellular function, and organismal adaptation and survival.  

Research

A major obstacle to predicting plant responses to multiple environmental forcing factors is our lack of knowledge of the trade-offs between plant biomass allocation and nutrient acquisition. Thus, we believe that it will be necessary to factor in the attendant responses of mycorrhizal fungi to multiple-factor stressors. The ability of plants to adapt or respond to a changing environment is dependent on homeostatic capacities that minimize the cost of growth and biomass allocation. Plants’ responses to environmental stresses, such as nutrient limitation or anthropogenic effects suggest that they have a centralized system of stress response involving changes in nutrient and water use, carbon allocation, hormonal balances, and reliance on the mycorrhizal symbiosis.

Mycorrhizal fungi contribute to community processes and functions at various hierarchical organizational levels, through their establishment of linkages and feedbacks between whole-plants and nutrient cycles. Even though these fungal mediated feedbacks and linkages involve lower-organizational level processes (e.g., photo-assimilate partitioning, interfacial assimilate uptake and transport mechanisms; disease resistance), they influence higher-organizational scales that affect both community and ecosystem behavior. Hence, incorporating mycorrhizal fungi into research directed at understanding of the diverse environmental issues confronting society will require knowledge of how these fungi respond to or initiate changes in vegetation dynamics, soil fertility, or both.

My research addresses mechanisms controlling the growth and allocation of mycorrhizal fungi. Our premise is that predictions about whole-plant responses, especially those associated with multiple forcing factors, will require a better understanding of how mycorrhizal fungi respond to alterations in host allocation of assimilated carbohydrates and soil nutrients and how fungal responses feed back to the host.

Research

Dr. Meyer current work focuses on the analysis of shotgun metagenomics data sets and on the MG-RAST community portal for metagenomics. Shotgun metagenomics is benefitting directly from the current advances in sequencing technology, leading to dramatic growth in the number scientists using this approach and the number and size of the data sets being produced. He also has an interest in microbial genomics and the analysis of complete microbial genomes and is a member of the RAST project.

Research

Alegre, ML and McNerney, ME. (2007) NK cell subsets in allograft rejection and tolerance. Current Opinion in Organ Transplantation. 12:10-16.

Lee, KM*, Forman, J*, McNerney, ME*, Stepp, S, Kuppireddi, S, Guzior, D, Latchman, YE, Sayegh, MH, Yagita, H, Park, CK, Oh, SB, Wulfing, C, Schatzle, J, Mathew, PA, Sharpe, AH, and Kumar, V. (2006) Requirement of homotypic NK cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functions. Blood. 107:3181-3188. *Authors contributed equally.

McNerney, ME*, Lee, KM*, Zhou, P*, Molinero, L, Mashayekhi, M, Guzior, D, Sattar, H, Kuppireddi, S, Wang, CR, Kumar, V, and Alegre, ML. (2006) Role of natural killer cell subsets in cardiac allograft rejection. American Journal of Transplantation. 6:505-513. *Authors contributed equally.

McNerney, ME and Kumar, V. (2006) The CD2 family of NK cell receptors. Colonna, M and Vivier, E eds. Current Topics in Microbiology and Immunology. 298:91-120.

McNerney, ME, Guzior, D, and Kumar, V. (2005) 2B4 (CD244) – CD48 interactions provide a novel MHC class I-independent system for NK cell self-tolerance in mice. Blood. 106:1337-1340.

Kumar, V and McNerney, ME. (2005) A new self: MHC class I independent NK cell self-tolerance. Nature Reviews Immunology. 5:363-374.

McNerney, ME, Lee KM, and Kumar, V. (2005) 2B4 (CD244) is a non-MHC binding receptor with multiple functions on natural killer cells and CD8+ T cells. Molecular Immunology. 42:489-494.

Vaidya SV, Stepp SE, McNerney ME, Lee JK, Bennett M, Lee KM, Stewart CL, Kumar V, Mathew PA. (2005) Targeted disruption of the 2B4 gene in mice reveals an in vivo role of 2B4 (CD244) in the rejection of B16 melanoma cells. Journal of Immunology. 174:800-807.

Lee, KM*, McNerney, ME*, Stepp, SE, Mathew, PA, Schatzle, JD, Bennett, M, and Kumar, V. (2004) 2B4 acts as a non-MHC binding inhibitory receptor on mouse NK cells. Journal of Experimental Medicine. 199:1245-1254. *Authors contributed equally.

Yi, Y, McNerney, M, and Datta, SK. (2000) Regulatory defects in Cbl and Mitogen-Activated Protein Kinase (Extracellular Signal-Related Kinase) pathways cause persistent hyperexpression of CD40 Ligand in human lupus T cells. Journal of Immunology 165: 6627-6634.

Research

Toxoplasmosis causes loss of sight, hearing and brain damage in congenitally infected individuals. It also causes substantial morbidity and mortality in individuals immunocompromised by organ transplantation, malignancy or vasculitis and their therapy or AIDS.

Our laboratory has discovered Toxoplasma gondii specific secretory IgA (mouse and human) which can block T. gondii invasion of enterocytes, T. gondii specific cytolytic T cells, and demonstrated that a temperature sensitive mutant T gondii can confer protection against peroral and congenital T. gondii infection in a murine model. We have also demonstrated marked differences in genetic susceptibility to this infection and identified some of the responsible genetic loci. In separate experiments, we have discovered T. gondii antigen specific unresponsiveness in congenitally infected infants.

Our current experiments involve protective and harmful immune responses (in mice and humans) and constructing recombinant vectors for delivery of those epitopes that elicit protective immunity. Specifically, our research involves (1) defining T.Gondii epitopes recognized by protective CTL lymphocytes, (2) determining whether the critical protective immune function is cytolytic T cell function or gamma interferon production or both, and (3) incorporating the genes which encode proteins which contain epitopes that elicit protection into a DNA vaccine. This construct will be used to immunize human MHC transgenic mice (on a susceptible H-2b background) to determine whether it will protect against peroral and congenital infection.

We also are characterizing immunogenetics and pathogenesis and protection in this infection.

Research

The Lussier Research Group conducts research in the emerging field of phenomics, using computation to model phenotypes, integrate genomic with phenotypic datasets, and analyze phenomes in order to accurately individualize the understanding, the prediction, and the treatment of diseases.

- Modeling Phenotypes for comparative biology is our first focus. We design methods to automate the processes of integration, organization, visualization and datamining of non-molecular phenotypic data and knowledge.

- Comparative Phenomics, understanding phenotypic-genotypic interactions , is the second major focus of our research group.

- Integrating Biomedical Datasets across heterogeneous and semi-structured databases is our third complementary focus.  

Research

The Matlin Laboratory studies the biogenesis of epithelial polarity in both cultured cells and epithelial injury models.

Research in the Matlin Laboratory is focused on understanding the biogenesis of apical-basal polarity in epithelial cells. Epithelial polarity is critical for the normal functioning of epithelial organs, such as the kidney and the gastrointestinal tract. Furthermore, the loss of epithelial polarity is an important contributor to the pathogenesis of disease following epithelial injury and carcinogenesis.

A primary current project is focused on deciphering how interaction of epithelial cells with the underlying extracellular matrix helps to orient the apical-basal axis in cells. In particular, we are examining how two forms of laminin, a major protein of the basal lamina, affect cell adhesion, migration, proliferation, and, ultimately polarization. One of these is laminin 332 (formerly known as laminin 5), a truncated form implicated in epithelial regeneration after injury. The other is laminin 511 (formerly known as laminin 10), a network-forming laminin whose assembly is believed to be required for polarization. Experiments in this area are conducted using Madin-Darby canine kidney (MDCK) cells, the leading mammalian model for the study of polarization mechanisms.

A variety of other projects are also underway or are being planned. These include examination of laminin involvement in regeneration of the renal tubular epithelium after acute or chronic kidney injury using mouse models, investigation of the roles of laminins in cancer metastasis, and determination of the effects of laminin 332 on network assembly of laminin 511 using atomic force microscopy. In addition, our laboratory is very interested in developing computational approaches to model epithelial polarization on a systems level.

Aside from work in the laboratory, we are also conducting research on the history and philosophy of cell biology, particulary in the modern period after 1970, and the relationship of the discipline of cell biology to the parallel discipline of molecular biology.

Research

A fundamental problem in evolutionary biology is how genes with novel functions originate. My research focuses on this problem, although I am also interested in other issues of molecular evolution. Interest in evolutionary novelties can be traced back to the time of Darwin. However, studies of the origin and evolution of genes with new functions have only recently become possible and attracted increasing attention. Although conceptual revolution is always what we wish to pursue, the available molecular techniques and rapidly expanded genome data from many organisms mean that searching for and characterizing new genes is no longer a formidable technical obstacle. Molecular and evolutionary studies have provided powerful analytical tools for the detection of the processes and mechanisms that underlie the origin of new genes. Two levels of questions about this process can be defined. First, at the level of individual new genes, what are the initial molecular mechanisms that generate new gene structures? Once a new gene arises in an individual genome in a natural population, how does it spread throughout an entire species to become fixed? And, how does the young gene subsequently evolve? Second, at the level of the genome, how often do new genes originate? If new gene formation is not a rare event, are there any patterns that underlie the process? And, what evolutionary and genetic mechanisms govern any such patterns? I believe that an efficient approach to these questions is to examine young genes because their early processes of origination are directly observable. Pursuit of these problems requires an integrated approach incorporating molecular, genomic and population analyses. My lab applies such an approach to our studies. Using experimental and computational genomic analysis, we identified numerous new genes in Drosophila and mammalian genomes. Using molecular analysis, we revealed some important molecular evolutionary mechanisms responsible for their current gene structures. By evolutionary genetic analysis, we observed a significant role of the adaptive evolution in the determination of the fate of those new genes. Interesting patterns are observed associated with these new genes. I see questions there, challenges there, joys there…

Research

My lab’s research interests are in the field of evolution and development, and more specifically the evolution of the deuterostomes. This major metazoan lineage is made up of four major groups; chordates, echinoderms, hemichordates, and a very recent addition; Xenoturbellida . The early evolutionary history of the deuterostomes remains poorly understood and surprisingly even the evolutionary origins of our own phylum, the chordates, remains a major puzzle for zoologists. This uncertainty is partly due to a poor early fossil record for this lineage, but also due to the enormous morphological disparity in adult body plans between the major groups. Reconstructing the body plan of a plausible common ancestor based on extant forms is fraught with difficulties. My work attempts to make some headway in this area, and has focused on investigating the role of developmental genes that underlie these divergent body plans and morphologies in hemichordates and echinoderms. By comparing the expression and roles of these genes to their orthologues in chordates I am trying to gain insights into early events in deuterostome evolution.

We have largely focused on the origins and early evolution of the vertebrate brain and central nervous system. While the brain is clearly a key innovation of our phylum, we understand very little about its evolutionary origins outside of the chordates. Much progress has been made in identifying the early molecular genetic program of brain patterning and morphogenesis in vertebrate model systems. We have been developing the hemichordate Saccoglossus kowalevskii as a less complex developmental model for addressing early evolution and origins of the vertebrate nervous system. As a phylum closely related to chordates, hemichordates are the most promising group for addressing issues of chordate brain evolution and development. Unlike chordates, their nervous system is organized on the basis of a nerve net rather than a centralized structure. We have been investigating conserved gene regulatory networks involved in the regionalization of the vertebrate brain during hemichordate development and find a remarkable conservation of gene expression despite the organizational disparity between the nervous systems of both groups. By this comparative approach, we are further developing this work to determine what aspects of central nervous system patterning predate the spectacular morphological elaboration of the vertebrate brain, and were present in the common ancestor of hemichordates and chordates.

More recently we have begun two new lines of research: 1. The evolution of mesoderm. 2. Evolution of asymmetry within the deuterostomes.

Research

Transcription regulation in LNCaP cells and nucleocytoplasmic trafficking of steroid hormone receptors.

Research

Primary interest is to look for connection between genetic factors and human psychiatric disorders or behaviors. Current research project is the genetic studies of bipolar disease (BD) using molecular genetics, genomics and bioinformatics approaches. We reported initial finding of association between G72 and BD. We developed a series of bioinformatics tools for complex diseases study (http://bioinfo.bsd.uchicago.edu). Animal model, expression profiling, DNA copy number studies, and new bioinformatics tools are under development in this lab. Integration of the varieties of tools and data will hopefully lead us to the identification of some disease susceptibility genes. Such findings will lead to improvement of the diagnosis and treatment of psychiatric diseases.

Research

Implementation of high-throughput technologies to study hepatocyte growth factor receptor signaling pathways.

Research

My major interest is in the processes and mechanisms of molecular and genomic evolution, using both experimental and theoretical approaches. Current projects include:

I. Evolution of gene regulation.

The importance of regulatory evolution has been proposed long ago (for instance, in the conspicuous morphological differences between human and chimp), but it has not been well studied due to experimental limitations. Making use of recent advances we are pursuing the following studies:

(1) Evolution of gene regulation in yeast strains and species. Our major question is whether evolution of gene regulation is mainly due to changes in cis elements or in trans factors. We are using microarrays and real time PCR to study expression differences, computational analysis of genomic data to identify sites of interest, and site-directed mutagenesis and fitness assays to test effects of regulatory changes.

(2) Evolution of gene expression patterns in mammals. Using data in the public domain, and in collaboration with other labs, we are investigating changes in tissue expression patterns between species or duplicate genes.

(3) Evolution of cis-regulatory modules and gene networks. Using statistical and experimental approaches we are identifying cis elements and gene networks, and studying how they have evolved.

II. Evolution of duplicate genes.

Gene duplication is a major source of raw material during genome evolution, and the analysis of duplicate genes provides insight into many evolutionary processes. We study patterns of duplicate gene survival across diverse genomes and what factors, such as gene structure, expression, or protein interaction, influence these patterns. We also study rates and mechanisms of structural and functional divergence in duplicate genes.

III. Development of statistical methods and computational analysis of genomic data.

The huge amount of genomic data currently available is a tremendous resource for understanding the organization and evolution of genomes. We are currently developing tools for analysis of segmental duplications, protein interaction data, and genomic

Bio

Her research focuses on the molecular analysis of the recurring chromosomal abnormalities in human leukemias and lymphomas, correlating specific abnormalities with morphological and clinical features and the development of risk-adapted therapy.

Research

Human tumors are characterized by recurring chromosomal abnormalities. During the past few years, the genes that are located at the breakpoints of a number of recurring chromosomal abnormalities in human tumors have been identified. Molecular analysis has revealed that alterations in the level of expression of these genes, or in the properties of the encoded proteins resulting from the chromosomal rearrangement, play an integral role in the process of malignant transformation.

My research interests are:

1) to identify the recurring chromosomal abnormalities in human tumors;

2) to correlate specific chromosomal abnormalities with morphological and clinical features of the neoplastic disease, such as response to therapy and survival;

3) to identify the genes located at the breakpoints of the recurring abnormalities using the techniques of molecular genetics, and to examine their function in malignant cells characterized by these chromosomal abnormalities;

4) to localize genes to human chromosomes by using the technique of in situ chromosomal hybridization and to examine the location of specific genes relative to the breakpoints of recurring abnormalities in hematopoietic neoplastic diseases; and

5) to examine the relationship of chromosomal fragile sites (loci which are prone to undergo breakage and rearrangement) and cancer-specific breakpoints.

Research

We are a mammalian biology lab interested in two major research topics:

- Genetic Basis of Human Brain Evolution
- Stem Cell Biology

Our other research interests include neurogenetics, bioinformatics, and developing technologies for high-throughput functional genomics.

Research

The Kron laboratory is a highly collaborative group of cell biologists, geneticists, biochemists and chemists. Our major basic research efforts are directed at 1) dissecting cyclin dependent kinase structure and function in yeast, 2) defining roles for chromatin modifications in DNA damage response, and 3) developing novel mass spectrometry methods for phosphoproteomics and high throughput screening. We also pursue translational projects directed at 1) developing Bcr-Abl assays for diagnostics and antagonists for therapeutics and 2) discovering inhibitors of cellular response to DNA double strand breaks as an approach to radiosensitization.

Research

Our laboratory is interested in the cellular and molecular biology of murine natural killer (NK) cells. These cells are believed to act as the first line of defense against tumors and viral infections. In addition they secrete a variety of cytokines including 1FN-g and GM-CSF that can influence the inflammatory response. Two aspects of NK cell biology are of particular interest to us: the development of NK cells from multipotent progenitor cells, and the identification of NK cell receptors and their ligands.

Research

The lab focuses on issues in molecular evolution, and especially on identifying forces governing the evolutionary process. The central effort has been to understand the evolution of the alcohol dehydrogenase locus (Adh) in Drosophila. We are studying the evolutionary process on three different time scales—-affecting populations, affecting species, and affecting long-term molecular evolution. At each scale we are attempting to distinguish whether natural selection contributes to the process, and if so, to identify the type of selection. Our work suggests that natural selection has an important role in shaping patterns of nucleotide polymorphism around the Adh locus and in regulating gene allozyme frequencies in natural populations.

Additional evidence for natural selection comes from a recent study of polymorphism on the fourth chromosome of Drosophila, a chromosome with no recombination. We find very low levels of silent and non-coding variation, suggesting regular occurrences of genetic hitchhiking caused by selective sweeps. We have also been able to show that natural selection is likely to be an important force in long-term protein evolution: there are more amino acid substitutions in Adh across species than can be accounted for by genetic drift alone. Much of the current work in the lab is attempting to test the generality of these findings by studying nucleotide variation within and between species for other loci.

Several projects in the lab involve the application of molecular techniques to evolutionary problems or mechanisms. Research projects I would be interested in supervising include all applications of molecular population genetics to the study of evolutionary mechanisms. I am also interested in the molecular genetics of species differences, especially as it pertains to the genetics of speciation.

Bio

Dr. Thomas Krausz is an expert pathologist with broad interests in tumor pathology including melanocytic tumors, soft tissue tumors, breast tumors, lung tumors and mesothelioma.

Research

The relationship between the persistence of neutrophil metabolic activity and the development of pulmonary fibrosis in animal models following pulmonary challenge with fibrogenic and non-fibrogenic inflammatory stimuli. Pathogenesis of shock caused by Gram-positive and negative bacteria. Develop sulphated dextrins as anti-HIV agents. Investigation of survival and maturation of human primordial ovarian follicles in vitro. Changes of extracellular matrix, integrins and expression of stem cell factor receptor in melanocytic tumors. The National Institutes of Health and the National Institute of Environmental Health Science have funded Dr. Krausz’s research

Research

1) One of our research interests centers around studying at atomic resolution the structural and functional properties that define molecular recognition systems that activate and regulate biological properties. In particular, we study the energetics of hormone-induced receptor activation and regulation of growth hormone and its receptor using X-ray crystallography, site-directed mutagenesis, phage display mutagenesis and biophysical analysis. We are asking two fundamental questions: What are the mechanisms and the energetics involved in the binding of a hormone to a cell-surface receptor that trigger biological responses in the cell? How can related hormones show both the binding versatility and finely honed specificity required for biological regulation? Using phage display we have discovered an allosteric coupling between the two receptor binding sites on growth hormone, and have produced growth hormone variants that work through a drastically reduced binding interface.

2) Chaperone-assisted crystallography- We use antibody engineering to produce antibody- protein complexes to facilitate crystallization of membrane proteins, functional RNAs and protein complexes that are recalcitrant to convention crystallization. Our engineering techniques are based on novel phage display libraries that use a reduced genetic code.

3) Functional fishing- We use enzyme active site affinity tags to isolate novel enzymes that are unique to organisms that live in extremely harsh environments. We are trapping and structurally characterizing DNA- repair enzymes that function under high radiation conditions.

4) Synthetic biology- We use a combination of peptide synthesis and phage display (biosynthetic phage display) to produce proteins with novel properties.

Research

The major goals of our research are to understand the molecular mechanisms underlying protein function at the atomic level and to exploit such knowledge to engineer proteins with novel shape and/or function.

Current research topics include:

(i) Molecular mechanisms of protein-protein interactions via engineering of small antibody mimics, “monobodies.” Specific binding is a fundamental aspect of protein function. This project was conceived on a concept that a binding site comprises a subset of surface residues that are strategically placed on a protein “scaffold”. We rationally design large combinatorial libraries of monobodies, which are built on a small scaffold of a fibronectin type III domain. We select monobodies with desired binding properties from the libraries and characterize them using biophysical tools. The current focus is on the role of conformational diversity in binding affinity and specificity. We are also applying this technology to structural genomics and cell biology.

(ii) Molecular mechanism of beta-sheet formation in peptide self-assembly. The formation of continuous beta-sheet is responsible for self-assembly of peptides (protein misfolding) associated with the so-called amyloid diseases (e.g. Alzheimer’s). However, the noncrystallin and insoluble nature of peptide self-assemblies makes their biophysical characterization extremely difficult. We overcome these fundamental difficulties by protein engineering. We have developed a model system that closely mimics the structure of peptide self-assembly using a unique, “single-layer” beta-sheet found in the OspA protein. These “peptide self-assembly mimics” allow us to apply standard biophysical tools to characterize the atomic structure and energetics of peptide self-assemblies in unprecedented resolution and precision. We also design nanomaterials using the self-assembly mimic system.  

Research

Dr. Kaminski is interested in developed magnetic and non magnetic nano and microcarriers for targeted delivery of therapeutics and removal of blood borne toxins. He has been collaborating with The University of Chicago Medical Center clinicians including Drs. Axel Rosengart, Richard Kraig, Ravi Salgia, Bahktair Yamini, and others to design carriers for particular disease. Dr. Kaminski is designing biodegradable carriers composed of hydrophilic and hydrophobic plastics that can carry hydrophilic or lipophilic drugs. By means of incorporating magnetic nanocrystals into the plastic substrate, one can manipulate the physical position of the drug carriers to target organs, image their position by MRI, or physically remove them from the blood flow via an extracorporeal magnetic filter also designed by our group. He is pursuiing joint funding for the Argonne and UC team from DOD, NIH, and private companies.

Research

Director, Structural Biology Center, Argonne National Laboratory (ANL)
and Associate Adjunct Professor, Northwestern University (.(JavaScript must be enabled to view this email address))
Andrzej Joachimiak is a biophysicist who works in the area of protein structure, a
critical aspect of drug design. Joachimiak and his team are working to improve
methods that determine protein structures including new techniques in protein
production, crystal growth, X-ray crystallographic structure.
The collaboration with private industry is extensive. According to ANL, 54
pharmaceutical and biotech firms worked with Joachimiak and other Argonne scientists at the Advanced
Photon Source to link structure to function in designing new and more effective drugs.
Joachimiak has filed for two patents relating to his work. He studied molecular biology at the Institute of
Biochemistry and Biophysics at the Polish Academy of Sciences, Warsaw, Poland and received M.S. and
Ph.D. degrees in Chemistry from University of A. Mickiewicz, Poznan, Poland.

Research

My research focuses on elucidating the transcriptional regulatory networks mediated by nuclear receptors in breast cancer cells. I am applying both experimental and computational genomics approaches to define nuclear receptor cistromes, to identify nuclear receptor co-regulators, and to construct the global regulatory networks.

Research

My research concerns primarily the analysis and interpretation of molecular variation within and between populations. The goal is to understand the evolutionary forces that have produced the observed patterns of variation within populations and between species. My work is entirely theoretical, focusing on the stochastic processes relevant to evolution in finite populations in which genetic drift, mutation, migration and selection may all be important. Monte Carlo computer simulations and methods of statistical inference are important aspects of the work. Much of my past work has focused on Drosophila data, in the future it is likely that human variation will be a major focus.

Bio

Ms. Herendeen is responsible for IGSB frontline communication, scheduling, events, ordering, payments and grants information

Research

Grant, fiscal, event and laboratory management for Dr. Kevin White and Dr. Andrey Rzhetsky.

Research

My research program focuses on describing patterns of avian diversity from different perspectives, across multiple time frames, throughout the taxonomic hierarchy and spanning geography. Fundamental to all these research areas are rigorous phylogenetic analyses.

I am actively collaborating with a number of other researchers to determine patterns of phylogeny among major lineages of birds (under NSF’s Assembling the Tree of Life). Despite the contributions birds have made to science in general, we actually have a very poor understanding of how the major lineages of birds are related to each other. The Early Bird project will use DNA sequence data from multiple nuclear loci, in combination with fossil and morphological data to solve some of these important issues in avian biology.

I am also interesting in describing patterns of genetic diversity within and among populations of tropical birds (in the Neotropics, Africa, and Madagascar) and relating those patterns to biogeographic histories of these regions and to efforts to conserve biodiversity.

I am also interested in the information content of different kinds of data (molecular, morphological, behavioral, ecological) for phylogeny reconstruction. I believe that there has been too little emphasis placed on the design of molecular studies (choice of taxa to be analyzed) and analyses of the information content of DNA sequence data in comparison to other kinds of phylogenetic data.

I would be pleased to supervise students interested in molecular systematics of birds at all hierarchical levels, especially those interested in Neotropical biogeography. The Field Museum has an excellent collection of birds (including genetic resources), as well as modern facilities for molecular systematics (Pritzker Lab) and morphometric/image analysis.

Research

Data intensive computing and data mining; high performance data management; high performance computing; persistent object stores; digital libraries; scientific databases; scientific computing; numerical and symbolic computing

Research

The overall goal of my research is to determine the molecular mechanisms by which female steroid hormones regulate development, differentiation and/or cellular proliferation and survival in hormone responsive tissues and cancers. Estrogens regulate the expression of diverse regulatory proteins and growth factors via one or both of two estrogen receptor subtypes (ERα & ERβ ). My lab is actively studying several aspects of ER action, including the role of phosphorylation in transcriptional activation of ER, the roles of ER-associated proteins in receptor-mediated responses, the molecular nature of transcriptional activation and/or repression in the regulation of target gene expression, nongenomic actions of estrogens, and the detailed structural requirements for ligand binding in ERα/β , especially in regard to discrimination between estrogen agonists and antagonists (SERMs).

Current areas of focus include: 1) defining the molecular/structural mechanisms by which SERMs elicit tissue-selective agonist or antagonist responses via one or both ER subtypes; 2) identifying novel ER subtype-selective SERMs via a combination of structure-based drug design and de novo drug discovery; 3) generating a mouse model in which ERα is replaced with a mutant ERα that does not recognize endogenous estradiol but will respond normally to a synthetic estrogen such as DES. This model will be useful for studying estrogen-regulated development of the reproductive tract, bone, cardiovasculature and CNS, and will also be used for studying the genesis and progression of hormone dependent mammary cancers; 4) creating mouse models in which ERα , ERβ or PR (progesterone receptor) are selectively knocked out in one or more tissues, especially the mammary gland. 4) Determining how ERα suppresses inflammation by inhibiting NF- k B induced cytokine responses, 5) identifying the relative contributions and mechanisms of transcriptional versus rapid, nongenomic ERα/β actions in estrogen target tissues. 6) Using animal models of spontaneous human breast cancer to study prevention and/or treatment with novel drugs and natural products, such as green tea. All of these projects have direct relevance and application to breast and uterine cancer genesis, progression, treatment and prevention, as well as to the development of compounds that can be used for hormone replacement therapy in postmenopausal women.

Research

Cytokinesis is mediated by an actin-based contractile ring that is attached to the overlying cell membrane. Cytokinesis is highly regulated in time and space. The contractile ring assembles in the cell cortex after anaphase onset at a site midway between the two poles of the mitotic spindle thereby ensuring that the two sets of chromosomes are equally partitioned into the two daughter cells. We are using the nematode C. elegans and cultured human cells as model systems to dissect this complex process. We are using a combination of forward and reverse genetics, biochemistry, and live cell imaging to address the following unsolved problems: How is the cleavage furrow positioned? How does the contractile ring assemble and function? How does the central spindle assemble and function? How is completion of cytokinesis achieved?

We are particularly interested in the assembly and function of the central spindle. Central spindle assembly begins at the metaphase to anaphase transition, when chromosomes move polewards on shrinking kinetochore microtubules. At this time, non-kinetochore spindle microtubules become bundled to form the central spindle. We discovered an evolutionarily conserved protein complex, centralspindlin, consisting of a Rho family GAP, CYK-4, and a kinesin like protein, ZEN-4, that is directly involved in central spindle assembly. The central spindle is essential for completion of cytokinesis and it also regulates cleavage furrow formation. We want to understand in mechanistic terms how this motor/RhoGAP complex functions to coordinate central spindle assembly and how it regulates early and late events in cytokinesis.

In C. elegans embryos, cleavage furrow formation requires either the central spindle or astral microtubules. These two supramolecular structures appear to regulate furrow formation by distinct molecular mechanisms that converge at the GTPase RhoA. We will identify the mechanisms that lead to local activation of RhoA.

Research

Our main goal is to understand the processes that generate Golgi stacks. The cisternal maturation model provides a conceptual framework for studying Golgi formation. This model postulates that new Golgi elements arise at transitional ER (tER) sites, which are specialized for the production of ER-to-Golgi transport vesicles. We have obtained evidence that in budding yeasts, Golgi distribution is a consequence of tER organization. In Saccharomyces cerevisiae, Golgi cisternae are dispersed throughout the cytoplasm and the entire ER network functions as tER, whereas in Pichia pastoris, ordered Golgi stacks are located next to discrete tER sites. We are analyzing these two yeasts in parallel with vertebrate cells. Our specific approaches are: (1) To characterize the inheritance and dynamics of Golgi cisternae in S. cerevisiae through a combination of genetics and 4D video microscopy. (2) To study tER organization and biogenesis in P. pastoris using genetics, molecular biology, video microscopy, and biophysical computer simulations. P. pastoris is an ideal model organism for these studies. (3) To explore tER organization and dynamics in vertebrate cells. This approach is revealing evolutionarily conserved mechanisms that generate tER sites.

A second project in the lab involves optimizing the red fluorescent protein DsRed. Like GFP, DsRed potentially has wide application as a reporter and fusion tag. However, wild-type DsRed matures very slowly, requiring more than 24 hours at 37 C to achieve maximal fluorescence. We overcame this problem by using directed evolution to create rapidly maturing DsRed variants, one of which is now marketed commercially as DsRed-Express. Wild-type DsRed also tetramerizes, limiting its usefulness as a fusion tag. Ongoing work is aimed at creating a monomeric DsRed variant that will be as versatile as GFP.

Bio

Conrad Gilliam studies the genetic determinants of common heritable disorders, including neuropsychiatric disorders such as schizophrenia, bipolar disorder and autism, as well as other multifactorial disorders such as celiac disease and cardiovascular disorders.

Research

My research focuses on the identification and characterization of heritable mutations that affect the nervous system. Research projects vary from genetic mapping of rare (Mendelian) disease mutations and characterization of their downstream consequences to the study of common heritable disorders using mouse models as well as genomic and bioinformatic approaches.

Research

Our research focuses on inter-primate comparisons at the sequence and expression levels with the long-term goals of identifying genomic regions of functional importance, understanding human gene regulatory processes and elucidating the genetic architecture of human-specific traits.

We are using a novel multi-species cDNA array to compare expression levels between different primate species without the confounding effect of sequence mismatches on hybridization intensity. Our goal is to identify genes whose regulation in humans has evolved under natural selection. Further experiments are aimed at understanding the mechanism of transcription regulation (cis or trans) for individual genes or genes involved in the same biochemical pathways.

A second project in the lab is the study of olfactory receptor (OR) genes. We are interested in the evolution of the OR gene family in humans, as well as in their expression and regulation, both in the olfactory epithelium as well as in other tissues (such as testis).

Bio

His research in computer science has led to the development of the Globus Toolkit open source Grid software, widely used in business and science.

Research

Ian Foster develops tools and techniques that allow people to use high-performance computers in innovative ways. He is the Associate Division Director for Mathematics and Computer Science at Argonne National Laboratory and oversees the Distributed Systems Laboratory, which operates at both the University of Chicago and at Argonne National Laboratory. The DSL serves as the nexus of the multi-institutional Globus Project, a research and development effort that provides the advances required to make collaborative computing successful in science, engineering, business and other areas. Globus technologies are used by thousands of researchers worldwide and form the basis of several dozen national and international collaborative computing projects.

In March 2006, Foster was appointed director of the Computation Institute, a joint project between the University and Argonne that addresses the most challenging computational and communications problems arising from a broad range of intellectual pursuits.

Foster’s honors include the Lovelace Medal of the British Computer Society and the Gordon Bell Prize for high-performance supercomputing.

Research

Our interests center on the molecular mechanisms by which signal transduction pathways are organized into specialized membrane domains. In addition to their known role in organizing receptors and downstream effectors into functional signaling complexes, such organized complexes function to integrate signaling activities from multiple pathways and to segregate simultaneous but distinct functions of a single pathway.

We study this question in Drosophila because of the utility of this system for studying the functions of individual genes via mutagenesis, and for examining the functional interactions between different genes that work together in a particular cellular or developmental process.

Research

The major focus of Dr. Dolan’s research has been in the area of DNA damage/repair of anticancer agents that has been extended to the pharmacogenetics of DNA damaging agents. Her laboratory has been involved with: 1) developing a DNA repair modulator that enhances alkylating agent chemotherapy that is currently in clinical trials; 2) determining the role of DNA repair in protecting against therapy related leukemia; 3) identifying heritable and nonheritable genes important in susceptibility to DNA damaging agents and 4) evaluating genetic variation in human metabolizing genes that may be important in determining variability in patient response/toxicity to these agents.

Research

My research is in text mining. The biomedical literature contains a deluge of information - in an attempt to keep up with the latest findings as presented in scientific publications, researchers in biomedicine almost daily search for papers related to their work, specific information within the papers and often are trying to make connections among information contained in different papers. My research interests include the development and evaluation of text mining systems (both algorithms and user interfaces), identifying information for database annotation, as well as document clustering based on both syntactic and semantic content. All aim at making the information hunt in the literature faster and more efficient. Currently, I am working in a Ludwig Institute of Cancer Research (LICR) project on cancer metastasis.

Research

Our group aims to characterize the amount and patterns of genetic variation in human populations, and to elucidate the forces that shape and maintain this variation. Forces such as demographic change or population structure exert genome-wide effects, while others such as natural selection result in locus-specific effects. As greater attention is focused on dissecting the genetic bases of common diseases, an understanding of the patterns of human sequence variation is recognized as a critical step toward improved approaches to disease mapping. Our group takes advantage of the diverse intellectual environment at the University of Chicago to integrate the knowledge from population genetics and disease mapping studies.

Our work on these questions began with the analysis of mitochondrial DNA sequence and microsatellite variation, and led us to propose that ancestral human populations experienced a major demographic expansion. More recently, we have been taking advantage of the proliferation of new genetic tools for population studies, to test increasingly complex and, thus, more realistic scenarios of population growth; for example, we can survey sequence variation and linkage disequilibrium in a number of independent regions of the human genome. Our survey includes ethnically diverse populations so that the effect of population structure on genetic variation may also be assessed. Our empirical work is complemented by extensive modeling of demography and population structure by computer simulations based on coalescent theory (in collaboration with R. R. Hudson - University of Chicago).

More recently, we are studying the evolution of a polymorphic variant contributing to type 2 diabetes susceptibility. This variant was identified in the laboratory of our collaborators, G. I. Bell and N. J. Cox (University of Chicago). An attractive hypothesis, called the “thrifty genotype” hypothesis, proposes that diabetes variants have evolved under the effect of positive natural selection. Because natural selection leaves a distinctive signature on the amount and pattern of sequence variation and linkage disequilibrium in the region linked to the selected site, we have designed a survey to detect this. It involves quantitative comparison of both sequence and haplotype variation, and the degree and pattern of inter-population differentiation, at this site versus that at neutrally evolving loci. In addition, we will investigate the degree and pattern of inter-population differentiation at this site and ask whether it differs from those observed at other neutrally evolving loci in the human genome.

We are also interested in pharmacogenetic polymorphisms. Drug metabolizing enzymes (DMEs) are particularly interesting subjects for evolutionary biologists, because of their role as mediators between the organism and the environment. Their function in the detoxification of xenobiotics implies that variability at these genes is under strong selective pressures and, because the chemical environment varies significantly with diet, climate, lifestyle, etc., a great deal of inter-ethnic differentiation is expected (and in fact observed) for DME polymorphisms. Carcinogens are also metabolized by DMEs; thus, variability at DME genes is likely to result in varying susceptibility to cancer. Our efforts in this area so far have concentrated on a common polymorphism in the promoter of the UGT1A1 gene which encodes the major bilirubin glucuronidation enzyme. This enzyme also detoxifies the active metabolite of a commonly-used anticancer agent (irinotecan). Based on a worldwide survey of variability at the UGT1A1 promoter, we detected extensive variability across the major ethnic groups which may underlie the variability of response to the anticancer agent. We are currently investigating whether UGT1A1 polymorphisms contribute to the susceptibility to different types of cancer and surveying sequence variation for evolutionary analyses. We anticipate that these studies will provide a better understanding of the role of glucuronidation in drug response and in the gene-by-environment interactions that underlie cancer susceptibility.

Research

The Dinner group develops and applies theoretical methods for relating cellular behavior to molecular properties. We are particularly interested in how proteins regulate access to genes in the context of the development of the immune system. Understanding how such complex behavior arises from physical and chemical features is a problem in fundamental statistical mechanics, but its solution has direct implications for treating autoimmune pathologies and improving gene therapy and vaccination strategies.

One feature that makes theoretical studies of cellular behavior challenging is that the relevant dynamics span a hierarchy of time and length scales ranging from Angstroms and femtoseconds to micrometers and minutes. Experiments are now beginning to bridge gaps in spatial and temporal resolution, and models are vital for design and interpretation of such measurements. Our research thus blends atomic-resolution simulations with coarse-grained numerical and analytical approaches, often in collaboration with experimental groups.  

Research

My laboratory is a computational “dry” lab. Our research focus is on the identification and characterization of genetic variation influencing susceptibility to complex disorders. We work on both the localization of the genetic variation, via linkage studies and linkage disequilibrium mapping, as well as on the analytic component to positional cloning of genes for complex disorders. There are ongoing collaborations with a variety of groups at the University of Chicago for which we contribute the genetic analysis, including both linkage and linkage disequilibrium mapping, and these include projects on type 1 and type 2 diabetes, asthma and related phenotypes, attention deficit hyperactivity disorder, schizophrenia, bipolar disorder, and autism. In addition, we have a primary focus on developing and extending methods for mapping genes for complex disorders. Currently, this research includes an emphasis on developing robust methods for taking gene-gene interaction into account in the context of linkage mapping, linkage disequilibrium mapping and positional cloning. We are also developing, extending and applying methods for linkage disequilibrium mapping using the decay of haplotype sharing approaches pioneered by our colleague and collaborator in the Dept. of Statistics, Mary Sara McPeek. We also have a major emphasis on developing approaches for identifying the genetic variation affecting susceptibility to complex disorders in the context of positional cloning studies. These methods focus on identifying the genetic variation associated with disease, as well as showing significant ability to partition the evidence for linkage, and seeks to distinguish the actual causal variation from genetic variation that is merely in linkage disequilibrium. These methods are being immediately applied in projects on type 1 and type 2 diabetes as well as asthma. Our group is also taking a leadership role in a large collaborative study on type 2 diabetes, in which we are attempting to combine data from all existing genome scans for type 2 diabetes for linkage mapping studies. This project has generated data on a scale that has not been possible for any individual group to do, and this massive data set has required development of some novel approaches for analysis, as well as revision of standard software for mapping. We have also recently initiated a research project designed to map and identify genetic variation affecting susceptibility to stuttering.

Finally, because of a long-standing collaboration with a colleague in the Dept. of Human Genetics, Carole Ober, we are interested in developing and extending methods for genetic analysis of large, inbred geneologies such as the Hutterites, which is a long-term, major focus of Dr. Ober’s laboratory.

Research

My primary project involves genome wide RNAi screening to help understand the complex mechanism behind estrogen mediated increased proliferation of breast cancer. During the last 2 years I have also helped to establish RNAi screening and set up the Cellular Screening Center for the Lab.  

Research

Dr. Conzen’s laboratory uses both molecular approaches and animal models to study mechanisms that contribute to the development and progression of human breast cancer. Current projects include 1) defining glucocorticoid receptor signaling pathways in breast epithelium, 2) determining the role of ubiquitin modification of cellular kinases in breast cancer survival signaling pathways and 3) using bioinformatic approaches to predict signaling pathways from large-scale time course microarray data.

Research

My current project is aimed at developing and applying highly parallel methodologies to systematically analyze protein interaction, expression, and post-translational modification during cellular signal transduction processes. By using this systems information, my interests are to develop computational models of cell signaling and use the modeling to logically design small molecule inhibitors to engineer the physiology of cells in health and disease.

Research

1. Using high-throughput western blot to study effect of natural compound on the progression of prostate cancer.
2. Using functional protein array to study down stream signaling of androgen receptor.
3. Using high-throughput western blot to study cross-talk between receptor tyrosine kinase and androgen receptor in prostate cancer cells.

Research

Dr. Chen’s major research interests is to conduct integrated analyses of cancer-�omics� on both protein-coding and non-coding genes (particularly, microRNAs) regarding both genetic and epigenetic changes in the development of leukemia and lymphoma, using various techniques, to obtain a more complete understanding of the complex genetic and epigenetic alterations in cancer development and to identify novel markers and targets for the diagnosis, prognosis prediction, and treatment of cancers. In addition, Dr. Chen is also interested in identifying leukemia-stem-cell-specific genetic and epigenetic changes on both protein-coding and non-coding genes. These genes and the relevant pathways could serve as therapeutic targets in the future to overcome the drug resistance problem.

Research

HGAC operations are managed by Research Laboratory Manager Marc Domanus. Mr. Domanus has a Masters in Molecular Biology and Genetics, and 7 years experience working in high throughput facilities and in the use of state-of-the-art automation equipment at Motorola Life Sciences and Nanosphere Inc. Mr. Domanus was instrumental in setting up the facility, developing reproducible protocols and establishing quality control measures. Under Dr. White, Dr. Meyer, and Marc’s guidance, the HGAC team helps users to determine the most effective and cost efficient approach to meet their research needs. A member of the core’s staff is assigned to each user and guides them from initial sample preparation through to the primary analysis of their resulting data.