The purpose of this Program Project Grant competitive renewal application entitled "Discovery &Development of Therapeutic Genes for CHF" is to enable a number of scientists at VMRF and UCSD to maintain an efficient, interactive and mutually reinforcing program of basic and translational research to promote the discovery and development of therapeutic genes for congestive heart failure (CHF) and other cardiovascular diseases. The Program will facilitate the transition from discovery to clinical application of new therapeutic genes. This model combines discovery research with practical "street-smart" preclinical development. Successfully attaining our goals will require separate but highly integrated Projects that contain the proper proportions f discovery research and focused preclinical development, an accomplished translational physiology Core, and an interactive group of VMRF and UCSD physician-scientists in an ideal environment. Our goals are to identify, perform mechanistic preclinical studies, and eventually to launch clinical trials of promising candidate genes. Strengths of our Program include: i) the breadth of our expertise across disciplines relevant to the goals of the NHLBI;2) the novelty of approaches ranging from bench science to translational studies using high-fidelity animal models of cardiovascular diseases;and 3) our previous success navigating the regulatory pathway from discovery to launching clinical gene therapy trials. Our Program, which is focused on fundamental mechanisms by which the failing heart can be treated (or heart failure avoided), includes three Projects: Project 1 (Dr. Hammond) will develop and test unique AC-related proteins as therapeutic agents for clinical CHF. Project 2 (Dr. Roth) will focus on the impact of cavelolin-3 and mitochondrial function in the pathophysiology and treatment of CHF;and Project 3 (Dr. Dillmann) will use gene transfer to attenuate adverse glycosylation of calcium-related proteins and resolve mitochondrial abnormalities in CHF. Four Cores will support the Program: Digital Imaging (Dr. Farquhar);Vector Production (Dr. Miyanohara);Translational Systems (Dr. Hammond) and Clinical &Administrative (Dr. Hammond).

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Mcdonald, Cheryl
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Veterans Medical Research Fdn/San Diego
San Diego
United States
Zip Code
Pfeiffer, E R; Wright, A T; Edwards, A G et al. (2014) Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing. J Mol Cell Cardiol 76:265-74
Wang, Jiawan; Schilling, Jan M; Niesman, Ingrid R et al. (2014) Cardioprotective trafficking of caveolin to mitochondria is Gi-protein dependent. Anesthesiology 121:538-48
Lee, Kristen L; Hoey, David A; Spasic, Milos et al. (2014) Adenylyl cyclase 6 mediates loading-induced bone adaptation in vivo. FASEB J 28:1157-65
Tang, Tong; Lai, N Chin; Wright, Adam T et al. (2013) Adenylyl cyclase 6 deletion increases mortality during sustained *-adrenergic receptor stimulation. J Mol Cell Cardiol 60:60-7
Gao, Mei Hua; Lai, Ngai Chin; Tang, Tong et al. (2013) Preserved cardiac function despite marked impairment of cAMP generation. PLoS One 8:e72151
Tang, Tong; Hammond, H Kirk (2013) Gene transfer for congestive heart failure: update 2013. Transl Res 161:313-20
Rieg, Timo; Tang, Tong; Uchida, Shinichi et al. (2013) Adenylyl cyclase 6 enhances NKCC2 expression and mediates vasopressin-induced phosphorylation of NKCC2 and NCC. Am J Pathol 182:96-106
Gao, Mei Hua; Lai, N Chin; Miyanohara, Atsushi et al. (2013) Intravenous adeno-associated virus serotype 8 encoding urocortin-2 provides sustained augmentation of left ventricular function in mice. Hum Gene Ther 24:777-85
Lai, N Chin; Tang, Tong; Gao, Mei Hua et al. (2012) Improved function of the failing rat heart by regulated expression of insulin-like growth factor I via intramuscular gene transfer. Hum Gene Ther 23:255-61
Tang, T; Gao, M H; Hammond, H Kirk (2012) Prospects for gene transfer for clinical heart failure. Gene Ther 19:606-12

Showing the most recent 10 out of 54 publications