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Degrees: 1979 - MD - Yale - Medicine 1974 - BA - Harvard University - Biology, magna cum laude Department and Center Affiliations: Cardiovascular Division, Department of Medicine Medical Pharmacology Professional Societies: International Society for Heart Research American Physiological Society Fellow, American Heart Association Grad Group Affiliations and Specialties: Cell and Developmental Biology Molecular, Cellular, and Integrative Physiology Non-DBS Grad Group(s) - Pharmacology and Toxicology Publications: Chang, J, A.A. Knowlton, J.S. Wasser (2001) Activation of the heat shock response: Relationship to energy metabolites. Am. J. Physiol. 280:H426-H433. Chang, J, J.S. Wasser, A.A. Knowlton. (2001) Activation of HSF by Stretch-Activated Channels in Rat Hearts. Circulation 104:209-214. Knowlton, A.A. (2001) Mutation of amino acids 566-572 (KKKVLDK) inhibits nuclear accumulation of heat shock protein 72 after heat shock. J. Mol. Cell. Cardiol.33:49-55. Knowlton, A.A. and L. Sun (2001) Heat Shock Factor-1, Steroid Hormones and Regulation of Heat Shock Protein Expression in the Heart. Am. J. Physiol.280:H455-H464. Kirchhoff, S.R., S. Gupta, A.A. Knowlton. (2002) Cytosolic HSP60, apoptosis and myocardial injury. Circulation 105:2899-2904. Voss, M, J. Stallone, M. Li, P. Knuefermann, A.A.Knowlton. (2003) Gender Differences in the Expression of Heat Shock Proteins: The Effect of Estrogen. Am. J. Physiol. 285:H687-H692. Hamilton, K, S. Gupta and A.A.Knowlton.(2004) Estrogen and Regulation of Heat Shock Protein Expression in Female Cardiomyocytes: Cross-talk with NFkB Signaling. J. Mol. Cell. Cardiol 36:579-586. Trial, J, R.D.Rossen, and A.A.Knowlton.(2004) Inflammation and ischemia: Macrophages activated by fibronectin fragments enhance the survival of injured cardiac myocytes. Exp. Biol. Med. 229:538-545. Gupta,S. and A.A. Knowlton Cytosolic HSP60, Hypoxia, and Apoptosis. (2002) Circulation 106:2727-2733. Hamilton, K., Mbai, F.N., S. Gupta and A.A.Knowlton.(2004) Estrogen, Heat Shock Proteins and NFkB in human vascular endothelium. Atherosclerosis and Vascular Biology 24:1628-1633 Voss, M.R., S. Gupta, J.P. Stice, G. Baumgarten, Lu, L. J.M. Tristan and A.A.Knowlton. (2005) Effect of Mutation of Amino Acids 246-251 (KRKHKK) in HSP72 on Protein Synthesis and Recovery from Hypoxic Injury. Am. J. Physiol. 289:H2519-H2525. PMID: 16100242 Lu, L, Zhang, Z., Timofeyev, V., Zhang, Z., Young, J.N., Shin, H.S., Knowlton, A.A., & N. Chiamvimonvat. (2007) Functional Coupling of a Ca2+-Activated K+ Channel (SK2) to L-type Ca2+ Channels via alpha-Actinin2. Circ. Res. 100:112-120. PMID: 17110593 Ting, H., Stice,J. P., Schaff, U.Y., Hui, D.Y., Rutledge, J.C., Knowlton, A.A., Passerini, A.G., & S. I. Simon.(2007) Triglyceride-rich lipoproteins prime aortic endothelium for an enhanced inflammatory response to TNF-alpha. Circ. Res.100:381-390. PMID: 17234968 Gupta, S. & A.A. Knowlton.(2007) HSP60 Trafficking in Adult Cardiac Myocytes: Role of the Exosomal Pathway. Am. J. Physiol. 292:H3052-6. PMID: 17307989 Lin, L., S.C. Kim, Y. Wang, S. Gupta, B. Davis, S. I. Simon, G. Torre-Amione, and A.A. Knowlton. (2007) HSP60 in Heart Failure: Abnormal Distribution and Role in Cardiac Myocyte Apoptosis. Am. J. Physiol.293:H2238-47. PMID: 17675567 Hamilton, K.L., L. Lin, Y. Wang, and A.A.Knowlton.(2008) Effect of Ovariectomy on Cardiac Gene Expression: Inflammation and Changes in SOCS Genes Expression. Physiol. Genomics 32:254-263.PMID: 17986523 Research Interests: The research in our laboratory focuses in 2 areas related to the heat shock proteins (HSPs), and a developing area of research on aging, estrogen and mechanisms of cardiovascular disease. These three areas of research are: 1. Role of HSP60 in apoptosis and heart failure; We are interested in whether HSPs in heart failure paradoxically have a detrimental effect on the heart mediated by the immune system and an inflammatory response. 2. HSP60 and Cardiomyopathy - Work in this area focuses on exosomes, which we were the first to describe as released by heart cells and on HSP60 trafficking within the cell in the failing heart. We have reported abnormal localization of HSP60 with the cardiac myocyte in heart failure, and are studying the underlying regulation and function of abnormally distributed HSP60. 3. Estrogen, the HSPs and Aging - Initially this work focused on regulation of expression of HSPs by estrogen in cardiac myocytes and endothelial cells. This work has expanded to encompass interaction of aging and estrogen loss on the expression of HSP72 in the heart, and what impact this has on the response to ischemia. We use simulated ischemia of isolated cardiac myocytes, endothelial cell culture and failing hearts as models in our work. We are particularly interested in protein localization and post-translational modification, and the effect of disease on this. In studying particular aspects of HSP function we use various molecular methods including yeast-2-hybrid, site-directed mutagenesis and overexpression systems to study the effects of these changes. Our overall goal is to better understand cardiovascular injury in order to develop better treatments. http://www.ucdmc.ucdavis.edu/pharmacology/FacultyPages/akfacultypage.html Laboratory Personnel: Molecular & Cellular Cardiology - Ricky (Le) Chen, Ph.D., postdoc, Sanjiv Gupta, Ph.D. Shayma Haq, research assistant, Sam Kobba, medical student, James Stice, BA, graduate student, Nina Siebenborn, medical student, Terren Trott, undergraduate Courses Taught: CLH 230 Molecular Mechanisms of Disease: Congestive Heart Failure - Term(s): Winter |