Anne Knowlton

image of Anne Knowlton



Pharmacology - Medicine
Cardiovascular Physio(IntMed)

Offices and Labs

GBSF 6317


1979 MD Medicine Yale
1974 BA Biology, magna cum laude Harvard University

Research Interests

Work in my laboratory focuses on the cardiovascular system.  I am interested in how  cardiovascular cells respond to injury/stress,  and how this effects function of the cardiac pump and vasculature.  Thus we focus on the cellular and molecular mechanisms of cardiovascular disease.  At this time our work is in three areas: 1.  Exosomes and intercellular signaling in cardiovascular disease.  2.  Cell senescence, aging and estrogen.  What are mechanisms underlying the development of cell senescence and can cell senescence be mitigated? Does estrogen modulate the development of senescence in cells?  What is the impact of senescent endothelial cells and their inflammatory output (SASP) on the aging brain?  3.  Mitochondrial dysfunction in heart failure.  Heart failure occurs when the cardiac pump is damaged, and the heart responds by dilating and hypertrophying in a deleterious manner.  Mitochondrial dysfunction, which leads to increased ROS production, among other things, is a critical aspect of heart failure.  We are interested in how the mitochondria changes in heart failure and the downstream effects of these changes.


Vice Chancellor's Faculty Award for Excellence and Achievement, University of California, Davis 2007
Albrecht Fleckenstein Memorial Award for Distinguished Contribution to Basic Research, International Academy of Cardiology, 2013
Distinguished Fellowship Award, International Academy of Cardiology, 2015

Department and Center Affiliations

Molecular & Cellular Cardiology, Cardiovascular Division, Department of Medicine
Medical Pharmacology


International Society for Heart Research
Fellow, American Physiological Society
Fellow, American Heart Association

CBS Grad Group Affiliations

Biochemistry, Molecular, Cellular and Developmental Biology
Molecular, Cellular, and Integrative Physiology

Specialties / Focus

Biochemistry, Molecular, Cellular and Developmental Biology
  • Cellular Responses to Toxins and Stress
Molecular, Cellular, and Integrative Physiology
  • Cardiorespiratory Physiology
  • Cellular Physiology
  • Molecular Physiology

Graduate Groups not Housed in CBS

Pharmacology and Toxicology (PTX)


Molecular & Cellular Cardiology
  • Hyun Tae Hwang, graduate student, Adam Poe, graduate student, Tingting Liu, graduate student, Lily Lee, research assistant


CLH 230 Molecular Mechanisms of Disease: Congestive Heart Failure (Winter)


1/17/2017 2:50:53 PM
  • 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.
  • 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
  • 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
  • Stice, J.P., J. Eiserich, and A.A. Knowlton.(2009) Role of Aging vs. Loss of Estrogen in the Reduction in Vascular Function in Female Rats. Endocrinology 150:212-219. PMID: 18787021
  • Chen, L., Q. Gong, J.P. Stice, A.A.Knowlton.(2009) Mitochondrial OPA1, Apoptosis and Heart Failure. Cardiovascular Research 84:91-99.PMID:19493956
  • Kim, S.C., J.P. Stice, L. Chen, J.S. Jung, Y. Wang, S. Gupta, G. Baumgarten, J. Trial and A. A. Knowlton.(2009) Extracellular Heat Shock Protein 60, Cardiac Myocytes and Apoptosis. Circulation Research 105:1186-1195.
  • Wang, Y., L. Chen, N. Hagiwara, and A. A. Knowlton.(2010) Regulation of Heat Shock Protein (HSP) 60 and 72 Expression in the Failing Heart. J. Mol. Cell. Cardiol. 48:360-366. PMID: 19945465
  • Stice, J.P., L. Chen, S.C. Kim, J.S. Jung, A. L. Tran, T. T. Liu and A.A. Knowlton. (2011) 17β-Estradiol, Aging, Inflammation and the Stress Response in the Female Heart. Endocrinology 152:1589-98.
  • Kobba, S., S.C. Kim, L. Chen, E. J. Kim, A. L. Tran, P. Knuefermann, and A.A. Knowlton.(2011) The Heat Shock Paradox and Cardiac Myocytes: Role of Heat Shock Factor. Shock 35(5):478-484.
  • Knowlton, A.A. and A.R. Lee (2012)  Estrogen and the Cardiovascular System.  Pharmacology and Therapeutics 135:54-70.  Invited review. PMID:22484805.

  • Chen, L, Tingting Liu, Alice Tran, Xiyuan Lu, Alexey A Tomilov, Vanessa Davies, Gino Cortopassi,  Donald M. Bers, Marcela Votruba,  Anne A. Knowlton. (2012)  OPA1 Mutation and Late Onset Cardiomyopathy: Mitochondrial Dysfunction and mtDNA Instability.  JAHA 1:doi: 10.1161

  • Malik, Z., K.S. Kott, A.J. Poe, T. Kuo, L. Chen, K. W. Ferrara and A.A. Knowlton. (2013) Cardiac Myocyte Exosomes: Stability, HSP60 and Proteomics.  Am. J. Physiol.  304(7):H954-65.

  • Tingting Liu, Le Chen, Eun Jung Kim, Diana Tran, Brett S. Phinney, Anne A. Knowlton. (2014)  Mitochondrial Functional and Proteomic Changes in Ischemic Heart failure. Life Sciences 101:27-36.

  • Knowlton, A. A.,  L. Chen and  Z. A. Malik (2014) Heart Failure and Mitochondrial Dysfunction: The Role of Mitochondrial Fission/Fusion Abnormalities and  New Therapeutic Strategies. Journal of Cardiovascular Pharmacology   63:196-206. Invited review.  PMID: 23884159. 

  • Heiserman, J.P., L. Chen,  BS Kim, S.C. Kim, A. L. Tran, N. Siebenborn, A.A. Knowlton. (2015) TLR4 Mutation  and  HSP60-Induced Cell Death in Adult Mouse Cardiac Myocytes.  Cell Stress and Chaperones  20(3):527-535.

  • Chongxiu Sun1, S. I. Simon, G. A. Foster, C. E. Radecke, H.T. Hwang, X. Zhang,  B. D. Hammock, N. Chiamvimonvat,  A. A. Knowlton.(2016) 11,12-Epoxyecosatrienoic Acids Mitigate  Endothelial Dysfunction Associated with Estrogen Loss and Aging: Role of Membrane Depolarization. J. Mol Cell Cardiol 94:180-188.