Dr. Åsa Gustafsson: Cardiovascular Research

Research Summary: Cardiovascular Disease

Dr. Gustafsson is interested in understanding the molecular pathways that regulate the life and death of cardiac myocytes. Activation of cell death pathways is a common occurrence in cardiovascular disease and contributes to the development of heart failure. Using genetic and molecular biology approaches, Dr. Gustafsson is elucidating the role that the Bcl-2 proteins play in regulating mitochondrial function and 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.

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. Heart failure may manifest years (>10 yrs) after initial exposure to the anthracyline. Cardiac stem cells provide a mechanism for minor repair and ongoing cell turnover in the heart. She has discovered that anthracyclines impair stem cell function in the young heart, resulting in a heart that is more susceptible to stress. Additional research examines how anthracylines interfere with stem cell function and whether stem cell can be used in cell replacement therapy to prevent cardiotoxicity.

Academic Achievements

Education: B.S. in Molecular Biology (1996) UCSD; Ph.D. in Biomedical Sciences, Dept. of Pharmacology (2001) UCSD; Postdoctoral Fellowship (2005) Scripps Research Institute.

Awards and Honors: Keith and Eva Killam Memorial Award, Western Pharmacological Society (2010); AHA BSC Outstanding Early-Career Investigator Award Finalist (2008); AHA Scientist Development Grant (2007); Young Investigator Award Winner, International Society for Heart Research American Section (2005); TRDRP New Investigator Award (2005); Beginning Grant-In-Aid, AHA Western States Affiliates (2005); AHA Postdoctoral Fellowship (2003); AHA Predoctoral Fellowship (1999).

Leadership Experience: AHA BCVS Leadership Committee member; Chair, AHA BCVS Early Career Committee.

Teaching

• Principles of Pharmacology & Physiology (SPPS 247).
• Contemporary Topics in Pharmacology (SSPPS 218A/B).

Key Contributions to Pharmaceutical Sciences

• Identified the mitochondrial death protein Bnip3 as a contributor to myocardial ischemia/reperfusion injury.
• Elucidated the importance of autophagy in removing damaged mitochondrial in cardiac cells.
• Discovered a role for anthracycline-mediated stem cell dysfunction in late onset cardiotoxicity.

Selected Recent Publications

Yitzhaki et al. (2009). Autophagy is Required for Preconditioning by the Adenosine A1 Receptor- Selective Agonist CCPA. Basic Res Cardiol. 104: 157-167.

Quinsay et al. (2010). Bnip3 mediates permeabilization of mitochondria and release of cytochrome c via a novel mechanism. J Mol Cell Cardiol. 48:1146-56.

Borillo et al. (2010). Pim-1 Kinase Protects Mitochondrial Integrity in Cardiomyocytes. Circ Res. 106:1265-74.

Huang et al. (2010). Juvenile exposure to anthracyclines impairs cardiac progenitor cell function and vascularization resulting in greater susceptibility to stress-induced myocardial injury in adult mice. Circulation 121:675-83.

Quinsay et al (2010). Bnip3-Mediated Mitochondrial Autophagy is Independent of the Mitochondrial Permeability Transition Pore. Autophagy 6:17-24.

Potential Collaborative Programs with the Pharmaceutical Industry

• Expertise in mitochondrial function and cell death signaling pathways in cardiac cells.
• Broad array of molecular and cellular laboratory techniques and in vivo mouse models of heart failure.