The Moskowitz laboratory is devoted to the genetic, genomic and molecular study of gene regulatory networks. A single overarching theme governs work in the Moskowitz laboratory: that understanding essential gene regulatory networks will unveil the molecular logic governing biological processes, and that understanding network disruption will inform the molecular basis underlying disease. We have recently pioneered approaches to identify non-coding RNAs as markers and modulators of enhancer function (Yang and Nadadur et al, 2017). The Moskowitz laboratory has focused on two areas of cardiac biology: (1) cardiac conduction with respect to cardiac arrhythmias and (2) cardiac development with respect to Congenital Heart Disease (CHD). In cardiac development, we investigate the genetic, genomic and developmental landscape of cardiac morphogenesis. We have identified an essential role for Hedgehog signaling in the cardiac development and congenital heart disease and contributed to a paradigm shift in the understanding of cardiac septation (e.g. Hoffmann et al., 2009; Xie et al., 2012; Zhou et al., 2017). We have recently identified a surprising and novel role for Hedgehog signaling in maintaining cardiac progenitor status and preventing premature differentiation (Rowton et al., 2018). In cardiac rhythm, we investigate the molecular mechanisms underlying the genetic basis of cardiac arrhythmias. We have defined the first molecular networks and linking GWAS loci in cardiac conduction (Arnolds et al, 2012), the first molecular network in Atrial Fibrillation, the most common arrhythmia world-wide (Nadadur et al., 2016) and the functional genomic mechanisms underlying genetic associations (Van den Boogaard et al., 2014).
Harvard Medical School
Boston, MA
Fellowship - Genetics
2006
Children's Hospital
Boston, MA
Fellowship - Congenital Heart Disease
2001
Brigham and Women’s Hospital
Boston, MA
Residency - Pathology
2000
University of Wisconsin, School of Medicine
Madison, WI
M.D./Ph.D. - Biochemistry
1998
Marine Biological Laboratory
Woods Hole, MA
- Embryology
1994
Wesleyan University
Middletown, CT
B.A. - Biochemistry/Molecular Biology
1988
Enhancer transcription identifies cis-regulatory elements for photoreceptor cell types.
Perez-Cervantes C, Smith LA, Nadadur RD, Hughes AEO, Wang S, Corbo JC, Cepko C, Lonfat N, Moskowitz IP. Enhancer transcription identifies cis-regulatory elements for photoreceptor cell types. Development. 2020 Feb 05; 147(3).
PMID: 31915147
Atrial fibrillation risk loci interact to modulate Ca2+-dependent atrial rhythm homeostasis.
Laforest B, Dai W, Tyan L, Lazarevic S, Shen KM, Gadek M, Broman MT, Weber CR, Moskowitz IP. Atrial fibrillation risk loci interact to modulate Ca2+-dependent atrial rhythm homeostasis. J Clin Invest. 2019 Nov 01; 129(11):4937-4950.
PMID: 31609246
Gata4 regulates hedgehog signaling and Gata6 expression for outflow tract development.
Liu J, Cheng H, Xiang M, Zhou L, Wu B, Moskowitz IP, Zhang K, Xie L. Gata4 regulates hedgehog signaling and Gata6 expression for outflow tract development. PLoS Genet. 2019 05; 15(5):e1007711.
PMID: 31120883
A calcium transport mechanism for atrial fibrillation in Tbx5-mutant mice.
Dai W, Laforest B, Tyan L, Shen KM, Nadadur RD, Alvarado FJ, Mazurek SR, Lazarevic S, Gadek M, Wang Y, Li Y, Valdivia HH, Shen L, Broman MT, Moskowitz IP, Weber CR. A calcium transport mechanism for atrial fibrillation in Tbx5-mutant mice. Elife. 2019 03 21; 8.
PMID: 30896405
Genetic variant at coronary artery disease and ischemic stroke locus 1p32.2 regulates endothelial responses to hemodynamics.
Krause MD, Huang RT, Wu D, Shentu TP, Harrison DL, Whalen MB, Stolze LK, Di Rienzo A, Moskowitz IP, Civelek M, Romanoski CE, Fang Y. Genetic variant at coronary artery disease and ischemic stroke locus 1p32.2 regulates endothelial responses to hemodynamics. Proc Natl Acad Sci U S A. 2018 11 27; 115(48):E11349-E11358.
PMID: 30429326
Evolutionarily conserved Tbx5-Wnt2/2b pathway orchestrates cardiopulmonary development.
Steimle JD, Rankin SA, Slagle CE, Bekeny J, Rydeen AB, Chan SS, Kweon J, Yang XH, Ikegami K, Nadadur RD, Rowton M, Hoffmann AD, Lazarevic S, Thomas W, Boyle Anderson EAT, Horb ME, Luna-Zurita L, Ho RK, Kyba M, Jensen B, Zorn AM, Conlon FL, Moskowitz IP. Evolutionarily conserved Tbx5-Wnt2/2b pathway orchestrates cardiopulmonary development. Proc Natl Acad Sci U S A. 2018 11 06; 115(45):E10615-E10624.
PMID: 30352852
A promoter interaction map for cardiovascular disease genetics.
Montefiori LE, Sobreira DR, Sakabe NJ, Aneas I, Joslin AC, Hansen GT, Bozek G, Moskowitz IP, McNally EM, Nóbrega MA. A promoter interaction map for cardiovascular disease genetics. Elife. 2018 07 10; 7.
PMID: 29988018
Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm.
Yang XH, Nadadur RD, Hilvering CR, Bianchi V, Werner M, Mazurek SR, Gadek M, Shen KM, Goldman JA, Tyan L, Bekeny J, Hall JM, Lee N, Perez-Cervantes C, Burnicka-Turek O, Poss KD, Weber CR, de Laat W, Ruthenburg AJ, Moskowitz IP. Transcription-factor-dependent enhancer transcription defines a gene regulatory network for cardiac rhythm. Elife. 2017 12 27; 6.
PMID: 29280435
Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription.
Werner MS, Sullivan MA, Shah RN, Nadadur RD, Grzybowski AT, Galat V, Moskowitz IP, Ruthenburg AJ. Chromatin-enriched lncRNAs can act as cell-type specific activators of proximal gene transcription. Nat Struct Mol Biol. 2017 Jul; 24(7):596-603.
PMID: 28628087
Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm.
Nadadur RD, Broman MT, Boukens B, Mazurek SR, Yang X, van den Boogaard M, Bekeny J, Gadek M, Ward T, Zhang M, Qiao Y, Martin JF, Seidman CE, Seidman J, Christoffels V, Efimov IR, McNally EM, Weber CR, Moskowitz IP. Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm. Sci Transl Med. 2016 08 31; 8(354):354ra115.
PMID: 27582060
Fellow of the American Heart Association
American Heart Association
2015
American Society of Clinical Investigation
American Society of Clinical Investigation
2014
Established Investigator Award
American Heart Association
2013
Louis N. and Arnold M. Katz Basic Research Prize
American Heart Association
2006