Cell adhesion molecules (CAMs) can mediate both cell-cell and cell-extracellular matrix (ECM) adhesions, as welt as govern the most fundamental properties within multicellular organisms, including cell morphology, migration, proliferation, differentiation, tissue morphogenesis, and embryonic development. Recent studies have now also revealed that mutations in genes encoding CAMs are found and associated with various diseases, including cancers, autoimmune diseases as well as cardiomyopathies This proposal is to test the central hypothesis that cardiac components of cell-cell (ie. plakoglobin), and/or cell-ECM (ie.PINCH) adhesion complexes play important roles in the etiology of arrhythmogenic right ventricular dysplasia/ cardiomyopathy (ARVD/C) and cardiac function and/or repair. Accordingly, the specific aims are:
Specific Aim 1 : To understand the molecular mechanism by which the human plakoglobin mutation results in Naxos disease, a recessive form of ARVD/C.
Specific Aim 2 : To determine whether the ARVD/C phenotype results from a cell autonomous requirement for plakoglobin in cardiomyocytes and to understand the role of ICD and cytoplasmic/nuclear plakoglobin in this disease.
Specific Aim 3 : To study the functional role of PINCH in cardiac development, injury, and repair.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL046345-19
Application #
8111950
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
19
Fiscal Year
2010
Total Cost
$310,717
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Bang, Marie-Louise; Gu, Yusu; Dalton, Nancy D et al. (2014) The muscle ankyrin repeat proteins CARP, Ankrd2, and DARP are not essential for normal cardiac development and function at basal conditions and in response to pressure overload. PLoS One 9:e93638
Israeli-Rosenberg, Sharon; Manso, Ana Maria; Okada, Hideshi et al. (2014) Integrins and integrin-associated proteins in the cardiac myocyte. Circ Res 114:572-586

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