Cardiovascular disorders (CVD), including coronary artery disease (CAD) and congenital hear diseases (CHD) are the leading causes of death in the United States. Despite strong contribution of genetic factors to CVD, very little is known about the underlying genetic causes of these diseases. We have embarked on high throughput sequencing and high throughput in vivo characterization of genes underlying CVD in outlier kindreds and in offsprings of consanguineous unions. Using whole-exome sequencing (WES) and state of the art analytic approaches, from linkage to gene set enrichment analysis, we have identified independent mutations that underlie CAD, metabolic syndrome and diverse CHD. Our success in identification of disease genes is in part due to access to unique disease populations across the world and the support of Yale Center for Mendelian Genomics. While we have devised inventive approaches for novel gene discovery, the distinctive feature of our laboratory is in pursuing the characterization of disease genes in vivo and its success in identifying novel disease pathways and targets for drug development. We have established high throughput techniques in the lab for functional characterization of identified human mutations in vitro and in vivo by employing novel gene editing techniques. Most recently, we have begun to investigate the epigenetic effects of aging, diet and physical activity on disease pathogenesis in human and animal models. Most notably, we have taken a step further and have initiated collaborative efforts with the industry in order to screen and characterize small molecules that can target identified disease pathways in order to rescue cardiovascular and metabolic traits. Our highly cited published work is an attest for the quality and the promising nature of the results we generate in the lab.

Public Health Relevance

Cardiovascular disorders (CVD) are the leading causes of death in the United States. Very little is known about their causes and how to prevent or properly treat them. We have identified mutations in humans that underlie diverse familial CVD and by making animal models of these disorders plan to study how the disease develops and how it can be treated.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R35)
Project #
5R35HL135767-02
Application #
9415452
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Luo, James
Project Start
2017-01-23
Project End
2023-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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