- Asst. Professor, Departments of Pediatrics and Pathology, The Institute for Molecular Pediatric Sciences
Phone: (773) 834-046
What are the molecular pathways that dictate cardiac morphogenesis? What is the ontogeny of Congenital Heart Disease (CHD), the number one birth defect world-wide? How did the cardiovascular system evolve into a form that can support terrestrial life? These intertwined questions are investigated in the Moskowitz laboratory.
Gene Discovery for CHD
We performed a gene discovery program using a forward genetic screen in mice to identify CHD-causing mutations (Kamp et al., 2010). Our initial work was the first to link cilia signaling to heart development (Friedand-Little et al., 2011). We have recently identified the CHD-causing mutations in several lines and are studying their effects on cardiac morphogenesis.
Cardiac Progenitor Specification and Cardiac Morphogenesis
Our recent work (Hoffmann et al., 2009) suggests that the molecular logic governing cardiac septation is firmly established within cardiac progenitors long before septum morphogenesis occurs. In current studies we are identifying the genetic programs required in cardiac progenitors for septum morphogenesis.
Cardiac Conduction System
The Cardiac Conduction System (CCS) is a specialized network of cardiomyocytes responsible for coordinating the rhythmic contraction of the heart. We have generated novel transgenic mouse lines for CCS-specific studies (Arnolds and Moskowitz, 2011). These novel CCS-specific reagents are being used to investigate the molecular control of CCS development and adult CCS function.
Our laboratory studies basic questions in cardiac development and function. We take biochemical, molecular, genetic, genomic and cellular approaches to these problems. Our aims are to elucidate general principles of organ morphogenesis using the heart as a model, understand the ontogeny of Congenital Heart Disease, and contribute to our understanding of cardiac evolution.
For more information, contact Ivan at email@example.com.
Friedland-Little JM, Hoffmann AD, Ocbina PJ, Peterson MA, Bosman JD, Chen Y,Cheng SY, Anderson KV, Moskowitz IP. A novel murine allele of Intraflagellar Transport Protein 172 causes a syndrome including VACTERL-like features with hydrocephalus. Hum Mol Genet. 2011 Jun 8. [Epub ahead of print] PubMed PMID: 21653639.
Arnolds DE, Chu A, McNally EM, Nobrega MA, Moskowitz IP. The emerging genetic landscape underlying cardiac conduction system function. Birth Defects Res A Clin Mol Teratol. 2011 Jun;91(6):578-85. doi: 10.1002/bdra.20800. Epub 2011 Apr 28. PubMed PMID: 21538814.
Arnolds DE, Moskowitz IP. Inducible recombination in the cardiac conduction system of mink:CreERT(2) BAC transgenic mice. Genesis. 2011 Apr 18. doi: 10.1002/dvg.20759. [Epub ahead of print] PubMed PMID: 21504046.
Moskowitz IP, Wang J, Peterson MA, Pu WT, Mackinnon AC, Oxburgh L, Chu GC, Sarkar M, Berul C, Smoot L, Robertson EJ, Schwartz R, Seidman JG, Seidman CE. Transcription factor genes Smad4 and Gata4 cooperatively regulate cardiac valve development. [corrected]. Proc Natl Acad Sci U S A. 2011 Mar 8;108(10):4006-11. Epub 2011 Feb 17. Erratum in: Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5921. PubMed PMID: 21330551; PubMed Central PMCID: PMC3053967.
Kamp A, Peterson MA, Svenson KL, Bjork BC, Hentges KE, Rajapaksha TW, Moran J, Justice MJ, Seidman JG, Seidman CE, Moskowitz IP, Beier DR. Genome-wide identification of mouse congenital heart disease loci. Hum Mol Genet. 2010 Aug 15;19(16):3105-13. Epub 2010 May 28. PubMed PMID: 20511334; PubMed Central PMCID: PMC2908466.
Hoffmann AD, Peterson MA, Friedland-Little JM, Anderson SA, Moskowitz IP. sonic hedgehog is required in pulmonary endoderm for atrial septation. Development. 2009 May;136(10):1761-70. Epub 2009 Apr 15. PubMed PMID: 19369393; PubMed Central PMCID: PMC2673765.
Moskowitz IP, Kim JB, Moore ML, Wolf CM, Peterson MA, Shendure J, Nobrega MA, Yokota Y, Berul C, Izumo S, Seidman JG, Seidman CE. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell. 2007 Jun 29;129(7):1365-76. PubMed PMID: 17604724.