Anne A. Knowlton specializes in cardiology, with particular interests in atrial fibrillation and heart failure. She graduated from Harvard University magna cum laude with a degree in biology. After earning her medical degree from Yale University and doing her internship and residency training at Boston City Hospital, Dr. Knowlton completed a cardiology fellowship at Boston University Medical Center. She was honored with a National Research Award as a postdoctoral fellow at the Cardiovascular Institute at Boston University School of Medicine from 1984 to 1986.
Knowlton has research interests in heat shock protein, apoptosis, heart failure, estrogen and aging. She has written numerous papers and several book chapters on topics related to cardiovascular medicine and serves on the editorial board of the Journal of Heart Disease and Open Autoimmunity.
Synopsis: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.
Graduate Group Affiliations:
M.D., Yale University, New Haven, Connecticut, 1979
A.B., Harvard University, Boston, Massachusetts, 1974
Boston City Hospital, Boston, Massachusetts, 1980-82
Boston University Medical Center, Boston, Massachusetts, 1982-84
American Board of Internal Medicine, 1984
American Board of Internal Medicine, Cardiology, 1987
American Heart Association, Fellow
American Physiological Society, Fellow
Council on Basic Science, AHA
Fellow, American College of Cardiology
International Society for Heart Research
Honors and Awards
Vice Chancellor's Faculty Award for Excellence and Achievement, University of California, Davis, 2007
Patient Service Award, VA Medical Center, 2000
Select Recent Publications
Despa, S., K. B. Margulies, L. Chen, A.A. Knowlton, P. J. Havel, H. Taegtmeyer, D. M. Bers, and F. Despa, Hyperamylinemia contributes to cardiac dysfunction in obesity and diabetes - a study in humans and rats. Circ. Res. 2012;110(4):598-608
Stice, J.P., F.N. Mbai, L. Chen and A. A. Knowlton , Rapid Activation of Nuclear Factor-?B by 17?-Estradiol and Selective Estrogen Receptor Modulators: Pathways Mediating Cellular Protection. Shock, 2012; 38(2):128-136
Juhasz, B., S. Mukherjee, R. Gesztelyi, I. Lekli, U. Raychoudhury, J. Bardhan, S. Banerji, A.A. Knowlton, D. K Das, Vitamin E Isomers Tocotrienols Confer Resistance to Ischemic Injury in Hypercholesterolemic Hearts. Mol Cell Biochem. 2012; 360 (1-2):35-45
Kobba, S., S.C. Kim, L. Chen, E. J. Kim, A. L. Tran, P. Knuefermann, and A.A. Knowlton. The Heat Shock Paradox and Cardiac Myocytes: Role of Heat Shock Factor. Shock, 2011; 35(5):478-484
Stice, J.P., L. Chen, S.C. Kim, J.S. Jung, A. L. Tran, T. T. Liu and A.A. Knowlton. 17?-Estradiol, Aging, Inflammation and the Stress Response in the Female Heart. Endocrinology, 2011;152:1589-98
Gower, R. M., Wu, H., Devaraj, S., Jialal, I., Ballantyne, C.M., Knowlton, A.A., S. I. Simon. CD11c/CD18 expression is upregulated on blood monocytes during hypertriglyceridemia and enhances adhesion to VCAM. Atherosclerosis and Vascular Biology, 2011; 31:160-6
A.S. Pechenino, L. Lin, F. N. Mbai, A. R. Lee, X. M. He, J. N. Stallone and A. A. Knowlton. Impact of Aging vs. Estrogen Loss on Cardiac Gene Expression: Late Estrogen Replacement and Inflammation. Physiologic Genomics, 2011; 43:1065-1073
Filosto S, Fry W, Bardet K, Knowlton A.A., T. Goldkorn. Neutral sphingomyelinase 2 (NSMASE2) is a phosphoprotein regulated by calcineurin (PP2B). J. Biol. Chem. 2010;285:10213-22
Tuteja D, Rafizadeh S, Timofeyev V, Wang S, Zhang Z, Li N, Mateo RK, Singapuri A, Young JN, Knowlton AA, Chiamvimonvat N. Cardiac Small Conductance Ca2-Activated K Channel Subunits Form Heteromultimers via the Coiled-Coil Domains in the C Termini of the Channels. Circ Res. 2010;107:851-9
Wang, Y., L. Chen, N. Hagiwara, and A. A. Knowlton. Regulation of Heat Shock Protein (HSP) 60 and 72 Expression in the Failing Heart. J. Mol. Cell. Cardiol. 2010;48:360-366