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Appointments:
Assistant Professor
Department of Pathology
Department of Pediatrics
Institute for Molecular Pediatric Sciences
Committee on Molecular Medicine/MPMM
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Education:
M.D. Univ. of
Wisconsin
1998
Ph.D. Univ. of Wisconsin, Madison 1996
B.A. Wesleyan
University
1988
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Contact:
Phone: (773) 834-0462
Fax:
(773) 834-2132
E-Mail: imoskowitz@peds.bsd.uchicago.edu
Address:
The University of Chicago
AMB N314B, (MC 1059)
5841 South Maryland Avenue
Chicago, Illinois 60637
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Related Research Interests:
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Ivan Moskowitz, M.D., Ph.D.
Research Summary
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.
Selected Papers
Arad M, Moskowitz IP, Patel VV, Ahmad F, Perez-Atayde AR, Sawyer DB,
Walter M, Li GH, Burgon PG, Maguire CT, Stapleton D, Schmitt JP, Guo
XX, Pizard A, Kupershmidt S, Roden DM, Berul CI, Seidman CE, Seidman
JG. Transgenic mice overexpressing mutant PRKAG2 define the cause of
Wolff-Parkinson-White syndrome in glycogen storage
cardiomyopathy. Circulation. 2003 Jun 10;107(22):2850-6
Patel VV, Arad M, Moskowitz IP, Maguire CT, Branco D, Seidman JG,
Seidman CE, Berul CI. Electrophysiologic characterization
and postnatal development of ventricular pre-excitation in a mouse
model of cardiachypertrophy and Wolff-Parkinson-White syndrome, JACC
2003 42:942-951
Wakimoto H, Kasahara H, Maguire CT, Moskowitz IP, Izumo S, Berul
CI. Cardiac electrophysiological phenotypes in postnatal
expression of Nkx2.5 transgenic mice. Genesis. 2003 Nov;
37(3):144-50.
Moskowitz IP, Pizard A, Patel VV, Bruneau BG, Kim JB, Kupershmidt S,
Roden D, Berul CI, Seidman CE, Seidman JG. The T-Box
transcription factor Tbx5 is required for the patterning and maturation
of the murine cardiac conduction system. Development. 2004
131:4107-16.
Kontani K, Moskowitz IP, Rothman JH. Repression of cell-cell fusion by
components of the C. elegans vacuolar ATPase complex. Dev Cell.
2005 May;8(5):787-94.
Wolf, CM*, Moskowitz IP*, Arno S, Branco, DM, Semsarian C,
Bernstein SA, Peterson M, Maida M, Morley GE, Fishman GI, Berul
CI, Seidman CE and J G Seidman. Somatic events modify hypertrophic
cardiomyopathy pathology and link hypertrophy to arrhythmia. Proc
Natl Acad Sci U S A. 2005 Dec 13; 102(50):18123-8.
* These authors contributed equally.
Aru GM, Juraszek A, Moskowitz I, Van Praagh R. Tetralogy of
Fallot with congenital aortic valvar stenosis: the tetralogy-truncus
interrelationship. Pediatr Cardiol. 2006 May-Jun;27(3):354-9.
Y Feng, MH Chen, IP. Moskowitz, AM. Mendonza, L Vidali, F
Nakamura, DJ. Kwiatkowski, and CA. Walsh. Filamin A (FLNA)
is required for cell–cell contact in vascular development and cardiac
morphogenesis. Proc Natl Acad Sci U S A. 2006 Dec
26;103(52):19836-41.
Stroud DM, Darrow BJ, Kim SD, Zhang J, Jongbloed MR, Rentschler
S, Moskowitz IP, Seidman J,
Fishman GI. Complex genomic
rearrangement in CCS-LacZ transgenic mice. Genesis. 2007
45(2):76-82.
Moskowitz IP, Kim JB, Moore M, Wolf CM, Peterson M, Shendure J, Nobrega
M, Yokota Y, Beruel C,
Izumo S, Seidman JG, Seidman CE. A
Molecular Pathway including Id2, Tbx5, and Nkx2-5
Required for
Cardiac Conduction System Development. Cell. 2007. 129(7):1365-76
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Faculty and Research
Programs
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