The Gene and Linda Voiland School of Chemical Engineering and Bioengineering is hosting a seminar presented by Dr. Zhaokang Cheng, Assistant Professor, Department of Pharmaceutical Sciences, Washington State University, Mar. 5, at 4:10 p.m. in ADBF 1002/FLOYD 256 (Tri-Cities).
Zhaokang (ZK) received his Ph.D. degree in Biochemistry and Molecular Biology from Nankai University, where his research focus was on promoting the efficacy of stem cell-based therapies in heart dis-ease. After that he moved to the United States and performed research with Dr. Mark A. Sussman at San Diego State University, and Dr. Joan M. Taylor at the University of North Carolina at Chapel Hill as an American Heart Association postdoctoral fellow. He is currently an Assistant Professor at Washington State University College of Pharmacy. His main research interests are to understand how heart cells respond to stress and what approaches can be taken to protect these cells.
Regulation of cell death and survival in the heart
Heart disease, the leading cause of death in the United States, is frequently characterized by death of cardiac myocytes due to apoptosis and/or necrosis. Adult mammalian cardiac myocytes are highly differentiated cells with very limited self-renewal capacity, rendering the injured heart unable to repopulate with sufficient replacement myocytes. Understanding the mechanisms underlying cardiac cell death will allow the development of novel therapeutic strategies to counteract cell loss following myocardial injury and should greatly improve morbidity and mortality. Ongoing research in the Cheng laboratory is focused on identifying novel regulators of cardiomyocyte death using biochemical, molecular, cellular, genetic, physiological, and histological approaches, with an ultimate goal of developing preventive, diagnostic and therapeutic strategies for heart disease including heart attack, reperfusion injury, and anti-cancer drug-related cardiotoxicity.
To determine essential cellular signaling networks in calcium overload-induced necrosis, we carried out a high-throughput genome-wide RNAi screen in human muscle cells. Our screen uncovered a critical role of the cAMP-dependent protein kinase (PKA) pathway in the regulation of necrosis. Further mechanistic studies in primary cardiomyocytes revealed that activation of the p38 MAPK stress signaling mediates calcium overload-induced necrosis downstream of PKA.
With the rapid increase of cancer survivors due to improved diagnosis and therapy in the past decades, cancer treatment-related cardiotoxicity is becoming an urgent concern for modern society. The anti-cancer drug doxorubicin (DOX), one of the most effective chemotherapeutic agents to date, is known to cause cardiomyopathy through induction of cardiomyocyte apoptosis. We previously showed that the cyclin-dependent kinase (CDK) inhibitor p21 promoted resistance against DOX-induced apoptosis. Here, we identified CDK2 as a key determinant of DOX-induced apoptosis in cardiomyocytes. Activation of CDK2 is necessary for DOX-induced Bim expression and mitochondrial damage. Our results indicate that pharmacological inhibition of CDK2 may be an effective cardioprotective strategy against DOX-induced cardiotoxicity.
