Qin M. Chen
Associate Professor of Pharmacology
Ph.D., Clarkson University, New York, 1991
Life Sciences North 545
(520) 626-9126
qchen@email.arizona.edu
Research Interests
- Molecular mechanisms of oxidative injury and adaptation
- Stress signal transduction pathways
- Genomics and proteomics of stress response
- Cytoprotective agents
Research Activities
Our researach focuses on the molecular mechanisms of oxidative stress and pharmacological agents of cytoprotection. Oxidants are byproducts of aerobic metabolism. The level of oxidants increases as a result of radiation, intoxication of certain xenobiotics and disease states involving ischemic reperfusion or inflammatory response. Oxidative stress has been shown to contribute to aging, cancer and heart disease. Our research projects are: 1) Molecular Mechanisms of Oxidative Stress Response using human fibroblasts as an experimental model system. We characterize genes and proteins that are upregulated or altered by oxidants using genomic and proteomic approaches to identify critical molecules that control a series of cellular changes resulting from oxidant exposure such as premature senescence and apoptosis; 2) The Role of Oxidative Stress in Heart Failure. Pathological analyses often reveal apoptotic cardiomyocytes, hypertrophy of remaining cardiomyocyte, and fibrosis or hyperplasia of fibroblasts in failing hearts. We isolate cardiomyocytes and fibroblasts from the heart of experimental animals to determine the cellular and molecular changes that are produced by oxidants in these cell types.
Our studies indicate that oxidants can induce hypertrophy of cardiomyocytes in culture. Thorough analyses indicate a role of phosphatidylinositol 3 kinase, MAP kinases, AP-1 transcription factors, and cyclooxygenase-2 in oxidant-induced cardiomyocyte hypertrophy. In contrast to cardiomyocyte hypertrophy, fibrosis is a disease involving proliferation of fibroblasts and changes in the expression of extracellular matrix proteins and secreted proteases by fibroblasts. Genomic profiling, proteomic mining and transcription factor measurements are ongoing to determine the influence of cell type on molecular and cellular changes induced by oxidants and to search for critical targets that play a role in fibrosis or cardiomyocyte hypertrophy associated with oxidative stress.
An important emphasis of our laboratory is searching for pharmacological agents that serve as cytoprotectants. Recent studies have pointed to a role of apoptosis in heart failure associated with cardiomyopathy and myocardial infarction. Our laboratory has found that corticosteroids can prevent cardiomyocytes to undergo apoptosis in vitro. Genomic and proteomic analyses show elevation of certain antioxidant proteins and anti-apoptotic proteins induced by corticosteroid. Currently we are exploring the transcription factors regulating cell survival responses and validating our in vitro findings with in vivo experimental models of heart failure.
Selected Publications
Dilley TK, Bowden GT, Chen QM (in press) Induction of Premature Senescence with Oxidants Confers Tumor Promoter Activity of Normal Human Diploid Fibroblasts. Exp Cell Res.
Purdom S, Chen QM (2003) p66Shc: at the Crossroad of Oxidative Stress and Genetics of Aging (commissioned review article) Trends Mol Med, 9: 206-210.
Tu VC, Bahl JJ, Chen QM (2002) Signals of Oxidant Induced Cardiac Myocyte Hypertrophy: Key Activation of phosphatidylinositol 3 kinase and p70S6 kinase. J Pharmacol Exp Ther, 300: 1101-1110.
Chen QM, Merrett JB, Dilley T, Purdom S (2002) Down Regulation of p53 with HPV E6 Expression Inhibits Apoptosis but Induces Oncotic Cell Death Associated with Mitosis in Oxidant Response of Human Diploid Fibroblasts. Oncogene 21: 5313-5324.
Chen QM, Tu VC, Wu YW, Bahl JJ (2000) Hyodrogen Peroxide Dose Dependent Induction of Hypertrophy or Apoptosis of Rat Cardiomyocytes. Arch Biophys Biochem, 373:242-248.