Dr. Grossfeld is a highly trained, board-certified pediatric cardiologist who is devoted to studying the genetic basis of congenital heart disease. The purpose of this grant proposal is to obtain support to enable Dr. Grossfeld to become an independent investigator by the end of the proposed funding period. The proposed research will be performed in the laboratory of Dr. Anthony Wynshaw-Boris in the Department of Pediatrics at the University of California, San Diego. During this time, Dr. Grossfeld will receive the necessary training for incorporating human and animal genetic model system approaches for studying genes causing hypoplastic left heart syndrome (HLHS). UCSD and specifically, Dr. Wynshaw-Boris, provide an ideal environment that has been extraordinarily successful for promoting and developing similar research interests. The long-term goal of this project is to study the role of OBCAM and Neurotrimin, two members of the IgLON subfamily of genes, in cardiac development and in the generation of congenital heart defects, including HLHS. HLHS is one of the most severe congenital heart defects, accounting for 20% of all deaths in infants with congenital heart disease. To date, no causative gene for HLHS has been reported.
The specific aims of this project are:
Specific Aim 1) : Characterization of the expression of OBCAM and Neurotrimin in fetal and adult heart;
Specific Aim 2) : Alteration in the expression of OBCAM and Neurotrimin utilizing mouse and chicken genetic model systems, and Specific Aim 3): Mutation analysis for point mutations and microdeletions in OBCAM and Neurotrimin in patients with isolated heart defects that occur in Jacobsen syndrome, and for single nucleotide polymorphisms in OBCAM and Neurotrimin in patients with Jacobsen syndrome.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL070640-03
Application #
6867442
Study Section
Special Emphasis Panel (ZHL1-CSR-M (F2))
Program Officer
Commarato, Michael
Project Start
2003-04-01
Project End
2008-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
3
Fiscal Year
2005
Total Cost
$121,770
Indirect Cost
Name
University of California San Diego
Department
Pediatrics
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Herrick, Nicole; Davis, Christopher; Vargas, Lisa et al. (2017) Utility of Genetic Testing in Elite Volleyball Players with Aortic Root Dilation. Med Sci Sports Exerc 49:1293-1296
Ye, Maoqing; Parente, Fabienne; Li, Xiaodong et al. (2014) Gene-targeted deletion of OPCML and Neurotrimin in mice does not yield congenital heart defects. Am J Med Genet A 164A:966-74
Ye, Maoqing; Coldren, Chris; Liang, Xingqun et al. (2010) Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice. Hum Mol Genet 19:648-56
Ye, Maoqing; Hamzeh, Rabih; Geddis, Amy et al. (2009) Deletion of JAM-C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice. Am J Med Genet A 149A:1438-43