The research in our laboratory focuses in 4 areas related to the protective properties of heat shock proteins (HSPs), and a developing area of research on aging, estrogen and mechanisms of cardiovascular disease. These four areas of research are: 1) Mechanisms underlying the protective properties of HSP72 in the cell, with particular focus of localization of HSP72 to the nucleus with stress; 2) 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. 3) Estrogen and the HSPs - regulation of expression of HSPs by estrogen in cardiac myocytes and endothelial cells. 4) estrogen, aging and the cardiovascular system. We are interested in the 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.

Selected Publications

Gupta,S. and A.A. Knowlton Cytosolic HSP60, Hypoxia, and Apoptosis. (2002) Circulation 106:2727-2733. Abstract.

Kirchhoff, S.R., S. Gupta, A.A. Knowlton. (2002) Cytosolic HSP60, apoptosis and myocardial injury. Circulation 105:2899-2904. Abstract.

Wang YH, KNowlton AA, Li FH, Borkan SC. Hsp72 expression enhances survival in adenosine triphosphate-depleted renal epithelial cells. (2002) Cell Stress and Chaperones 7:137-145. Abstact.

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. Abstract.

Bozkurt, B,I. Agoston, and A.A. Knowlton. (2003) Complications of inappropriate use of spironolactone in heart failure: When an old medicine spirals out of new guidelines. J. Amer. Coll. Cardiol. 41:211-214. Abstract.

Li, M, M.M. Ittmann, D.R. Rowley, A.A. Knowlton, Vaid, A.K., D.E. Epner. (2003) Glutathione S-transferase pi is upregulated in the Stromal Compartment of Hormone Independent Prostate Cancer. Prostate 56:98-105. Abstract.

Hamilton, K., Mbai, F.N., S. Gupta and A.A.Knowlton.(2004) Estrogen, Heat Shock Proteins and NF6B in human vascular endothelium. Atherosclerosis and Vascular Biology 24:1628-1633. Abstract

Hamilton, K, S. Gupta and A.A.Knowlton.(2004) Estrogen and Regulation of Heat Shock Protein Expression in Female Cardiomyocytes: Cross-talk with NF6B Signaling. J. Mol. Cell. Cardiol 36:579-586. Abstract.

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. Abstract.

Gupta, S. and A.A.Knowlton. (2005) HSP60. Bax, Apoptosis and the Heart. J. Cell. Mol. Med. 9:51-58. Abstract.

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 Heart Circ Physiol. 289:H2519-H2525. PMID: 16100242. Abstact.

Baumgarten, G., P. Knuefermann, G. Schuhmacher, V. Vervolgyi, J. von Rappard, U. Dreiner, K. Fink, C. Djoufack, A. Hoeft, C. Grohe, A.A. Knowlton, R. Meyer. (2006) Toll-like receptor 4, nitric oxide, and myocardial depression in endotoxemia. Shock 25:43-49. Abstract.

See: Complete List of Publications