The Skaggs School of Pharmacy & Pharmaceutical Sciences

Asa Gustafsson

Dr. Asa Gustafsson joined the Skaggs School of Pharmacy and Pharmaceutical Sciences in October 2009. Prior to coming to UCSD, she was an Assistant Professor at San Diego State University. She received her Ph.D. in Biomedical Sciences from the Department of Pharmacology at the University of California, San Diego, CA in 2001. Her postdoctoral training was done at The Scripps Research Institute in La Jolla with Dr. Roberta Gottlieb.

Research Interest

Activation of cell death pathways is a common occurrence in cardiovascular disease and contributes to the development of heart failure. We are interested in understanding the molecular pathways that regulate the life and death of cardiac myocytes. Using genetic and molecular biology approaches, we are elucidating the role that the Bcl-2 proteins play in regulating cell death in myocardial cells. The Bcl-2 family members are pro- and anti-apoptotic proteins that regulate the mitochondrial pathway of apoptosis in cells, including those of the myocardium. The discovery of new regulatory mechanisms of mitochondrial function and cellular survival will provide new knowledge that will be important to the design of new therapeutic approaches.

Another area of interest is to understand the mechanism(s) of late onset cardiotoxicity of anthracyclines. While anthracyclines are among the most effective chemotherapeutic agents commonly used in both children and adults, they are problematic because they are associated with cardiotoxicity. Unfortunately, children are more vulnerable to anthracycline-induced myocardial impairment than adults, and are at higher risk for heart failure. Heart failure may manifest years (>10 yrs) after initial exposure to the anthracyline. To understand this problem, we have established a mouse model of late onset anthracycline cardiotoxicity. Cardiac stem cells provide a mechanism for minor repair and ongoing cell turnover in the heart. Our data suggest that anthracyclines impair stem cell function in the young heart, resulting in a heart that is more susceptible to stress. We are currently investigating exactly how anthracylines interfere with stem cell function and whether we can use stem cell replacement therapy to prevent cardiotoxicity.

Selected Publications

Kubli, D.A., Ycaza J.E., and Gustafsson, Å.B. Bnip3 mediates mitochondrial dysfunction and cell death via Bax and Bak. Biochem J. 405(3): 407-15, 2007.

Hamacher-Brady, A., Brady, N.R., Logue, S.E., Sayen, M.R., Jinno, M., Kirshenbaum, L.A., Gottlieb, R.A., and Gustafsson, Å.B. Response to myocardial ischemia/reperfusion injury involves Bnip3 and Autophagy. Cell Death Diff, 14(1): 146-57, 2007.

Gustafsson, Å.B., and Gottlieb, R.A. Heart Mitochondria: Gates of Life and Death Cardiovasc. Res. 77(2): 334-343, 2008.

Kubli, D.A., Quinsay, M, Huang, C., Lee, Y., and Gustafsson, Å.B. Bnip3 functions as a Mitochondrial Sensor of Oxidative Stress during Myocardial Ischemia and Reperfusion. Am J Physiol Heart Circ Physiol. 295(5): H2025-31, 2008.

Lee, Y., and Gustafsson, Å.B. Role of Apoptosis in Cardiovascular Disease Apoptosis 14(4): 536-48, 2009.

Yitzhaki, S., Huang, C., Lee, Y., Gustafsson, Å.B., Mentzer, Jr. RM, and Gottlieb R.A. Autophagy is Required for Preconditioning by the Adenosine A1 Receptor-Selective Agonist CCPA. Basic Res Cardiol. 104(2): 157-67, 2009.