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
Hedgehog-FGF signaling axis patterns anterior mesoderm during gastrulation.
Guzzetta A, Koska M, Rowton M, Sullivan KR, Jacobs-Li J, Kweon J, Hidalgo H, Eckart H, Hoffmann AD, Back R, Lozano S, Moon AM, Basu A, Bressan M, Pott S, Moskowitz IP. Hedgehog-FGF signaling axis patterns anterior mesoderm during gastrulation. Proc Natl Acad Sci U S A. 2020 Jul 07; 117(27):15712-15723.
PMID: 32561646
Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation.
van Ouwerkerk AF, Hall AW, Kadow ZA, Lazarevic S, Reyat JS, Tucker NR, Nadadur RD, Bosada FM, Bianchi V, Ellinor PT, Fabritz L, Martin JF, de Laat W, Kirchhof P, Moskowitz IP, Christoffels VM. Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation. Circ Res. 2020 Jun 19; 127(1):34-50.
PMID: 32717170
ZO-1 Regulates Intercalated Disc Composition and Atrioventricular Node Conduction.
Dai W, Nadadur RD, Brennan JA, Smith HL, Shen KM, Gadek M, Laforest B, Wang M, Gemel J, Li Y, Zhang J, Ziman BD, Yan J, Ai X, Beyer EC, Lakata EG, Kasthuri N, Efimov IR, Broman MT, Moskowitz IP, Shen L, Weber CR. ZO-1 Regulates Intercalated Disc Composition and Atrioventricular Node Conduction. Circ Res. 2020 Jul 03; 127(2):e28-e43.
PMID: 32347164
Transcriptional Patterning of the Ventricular Cardiac Conduction System.
Burnicka-Turek O, Broman MT, Steimle JD, Boukens BJ, Petrenko NB, Ikegami K, Nadadur RD, Qiao Y, Arnolds DE, Yang XH, Patel VV, Nobrega MA, Efimov IR, Moskowitz IP. Transcriptional Patterning of the Ventricular Cardiac Conduction System. Circ Res. 2020 Jul 17; 127(3):e94-e106.
PMID: 32290757
Phosphorylated Lamin A/C in the Nuclear Interior Binds Active Enhancers Associated with Abnormal Transcription in Progeria.
Ikegami K, Secchia S, Almakki O, Lieb JD, Moskowitz IP. Phosphorylated Lamin A/C in the Nuclear Interior Binds Active Enhancers Associated with Abnormal Transcription in Progeria. Dev Cell. 2020 Mar 23; 52(6):699-713.e11.
PMID: 32208162
Chromatin-enriched RNAs mark active and repressive cis-regulation: An analysis of nuclear RNA-seq.
Sun X, Wang Z, Hall JM, Perez-Cervantes C, Ruthenburg AJ, Moskowitz IP, Gribskov M, Yang XH. Chromatin-enriched RNAs mark active and repressive cis-regulation: An analysis of nuclear RNA-seq. PLoS Comput Biol. 2020 02; 16(2):e1007119.
PMID: 32040509
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 02 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 11 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
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