John P. Cooke

John P. Cooke, MD, PhD

Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research, Department of Cardiovascular Sciences
Chair, Department of Cardiovascular Sciences
Professor of Cardiovascular Sciences, Academic Institute
Full Member, Research Institute
Director, Center for Cardiovascular Regeneration
Medical Director, Center for RNA Therapeutics
Houston Methodist
Weill Cornell Medical College

Center for Cardiovascular Regeneration


Dr. John P. Cooke is the Chair of the Department of Cardiovascular Sciences at the Houston Methodist Research Institute, Director of the Center for Cardiovascular Regeneration, and Medical Director of the RNA Therapeutics Program in the Houston Methodist DeBakey Heart and Vascular Center in Houston, Texas.

He trained in cardiovascular medicine and obtained a Ph.D. in physiology at the Mayo Clinic. He was recruited to Harvard Medical School as an assistant professor of medicine. In 1990, he was recruited to Stanford University to spearhead the program in vascular biology and medicine, and was appointed professor in the Division of Cardiovascular Medicine at Stanford University School of Medicine, and associate director of the Stanford Cardiovascular Institute until his recruitment to Houston Methodist in 2013.

Dr. Cooke has published over 500 research papers, position papers, reviews, book chapters and patents in the arena of vascular medicine and biology with over 30,000 citations. He has served on national and international committees that deal with cardiovascular diseases, including the American Heart Association, American College of Cardiology, Society for Vascular Medicine, and the National Heart, Lung and Blood Institute. He has served as president of the Society for Vascular Medicine, as a director of the American Board of Vascular Medicine, and as an associate editor of Vascular Medicine.

Description of Research

Dr. Cooke’s research program is focused on vascular regeneration, vascular cell identity and cell fate. The program is funded by grants from the National Institutes of Health, the American Heart Association, Cancer Prevention Research Institute, and industry.

The Cooke group aims to understand the mechanisms underlying epigenetic plasticity that are required for functional adaptation to cellular challenges.  Innate immune signaling causes global changes in the expression and activity of epigenetic modifiers with metabolic coupling that favors an open chromatin configuration.  The translational output of this work is vascular regeneration via therapeutic transdifferentiation using small molecules or mRNA. In his 25 years of translational vascular biology, Dr. Cooke first described and characterized the anti-atherogenic effects of endothelium-derived nitric oxide; the anti-angiogenic effect of the NO synthase inhibitor ADMA; the angiogenic pathway mediated by endothelial nicotinic acetylcholine receptors; the role for this pathway in states of pathological angiogenesis; and developed an antagonist of the pathway that was tested in clinical trials. His clinical research group has explored the use of angiogenic agents and adult stem cells in the treatment of peripheral arterial disease. More recently, his group has generated and characterized vascular cells diferentiated from iPSCs of patients with Progeria, to understand the role of telomere erosion in this condition of accelerated aging and vascular death. His group's applicaiton of mRNA encoding human telomerase to reverse aging in this condition, and other age-related diseases, is promising.

Areas Of Expertise

Regenerative medicine Stem cell Vascular disease Endothelium Telomeres and Aging
Education & Training

Clinical Fellowship, Mayo Graduate School of Medicine, Rochester, MN
Residency, Mayo Graduate School of Medicine, Rochester, MN
Internship, Mayo Graduate School of Medicine, Rochester, MN
MD, Wayne State Univ. School of Medicine
PhD, Mayo Graduate School of Medicine, Rochester, NY
Research Fellowship, Mayo Graduate School of Medicine, Rochester, NY

At the nexus of science, engineering, and medicine: Pasteur's quadrant reconsidered
Pettigrew, RI & Cooke, JP 2022, , PNAS nexus, vol. 1, no. 3, pp. pgac092.

Biomimetic Collagen Membranes Functionalized with mRNA-loaded Lipid Nanoparticles for Fibroblast Transdifferentiation to Endothelial Cells
Villarreal-Leal, RA, Williams, ME, Taraballi, F, Cooke, JP & Corradetti, B 2022, , FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 36.

Cancer treatment-induced NAD+ depletion in premature senescence and late cardiovascular complications
Banerjee, P, Olmsted-Davis, EA, Deswal, A, Nguyen, MT, Koutroumpakis, E, Palaskas, NL, Lin, SH, Kotla, S, Reyes-Gibby, C, Yeung, S-CJ, Yusuf, SW, Yoshimoto, M, Kobayashi, M, Yu, B, Schadler, K, Herrmann, J, Cooke, JP, Jain, A, Chini, E, Le, N-T & Abe, J-I 2022, , The journal of cardiovascular aging, vol. 2.

RBFOX2 is required for establishing RNA regulatory networks essential for heart development
Verma, SK, Deshmukh, V, Thatcher, K, Belanger, KAK, Rhyner, AM, Meng, S, Holcomb, RJ, Bressan, M, Martin, JF, Cooke, JP, Wythe, JD, Widen, SG, Lincoln, J & Kuyumcu-Martinez, MN 2022, , Nucleic Acids Research, vol. 50, no. 4, pp. 2270-2286.

Emerging nanotechnologies in cardiovascular medicine
Grattoni, A & Cooke, JP 2022, , Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 39, 102472.

Free Cholesterol Bioavailability and Atherosclerosis
Abe, RJ, Abe, JI, Nguyen, MTH, Olmsted-Davis, EA, Mamun, A, Banerjee, P, Cooke, JP, Fang, L, Pownall, H & Le, NT 2022, , Current Atherosclerosis Reports, vol. 24, no. 5, pp. 323-336.

Hospital-Based RNA Therapeutics
Damase, TR, Sukhovershin, R, Zhang, M, Kiss, DL & Cooke, JP 2021, . in mRNA Therapeutics: Springer.

Unsupervised learning for automated detection of coronary artery disease subgroups
Flores, AM, Schuler, A, Eberhard, AV, Olin, JW, Cooke, JP, Leeper, NJ, Shah, NH & Ross, EG 2021, , Journal of the American Heart Association, vol. 10, no. 23, e021976.

Nuclear S-nitrosylation impacts tissue regeneration in zebrafish
Matrone, G, Jung, SY, Choi, JM, Jain, A, Leung, HCE, Rajapakshe, K, Coarfa, C, Rodor, J, Denvir, MA, Baker, AH & Cooke, JP 2021, , Nature Communications, vol. 12, no. 1, 6282.

Telomerase therapy reverses vascular senescence and extends lifespan in progeria mice
Mojiri, A, Walther, BK, Jiang, C, Matrone, G, Holgate, R, Xu, Q, Morales, E, Wang, G, Gu, J, Wang, R & Cooke, JP 2021, , European heart journal, vol. 42, no. 42, pp. 4352-4369.

Telomerase therapy reverses vascular senescence and extends lifespan in progeria mice
Mojiri, A, Walther, BK, Jiang, C, Matrone, G, Holgate, R, Xu, Q, Morales, E, Wang, G, Gu, J, Wang, R & Cooke, JP 2021, , European heart journal, vol. 42, no. 42, pp. 4352-4369.

Nucleus-mitochondria positive feedback loop formed by ERK5 S496 phosphorylation-mediated poly (ADP-ribose) polymerase activation provokes persistent pro-inflammatory senescent phenotype and accelerates coronary atherosclerosis after chemo-radiation
Kotla, S, Zhang, A, Imanishi, M, Ko, KA, Lin, SH, Gi, YJ, Moczygemba, M, Isgandarova, S, Schadler, KL, Chung, C, Milgrom, SA, Banchs, J, Yusuf, SW, Amaya, DN, Guo, H, Thomas, TN, Shen, YH, Deswal, A, Herrmann, J, Kleinerman, ES, Entman, ML, Cooke, JP, Schifitto, G, Maggirwar, SB, McBeath, E, Gupte, AA, Krishnan, S, Patel, ZS, Yoon, Y, Burks, JK, Fujiwara, K, Brookes, PS, Le, N-T, Hamilton, DJ & Abe, J-I 2021, , Redox Biology, vol. 47, 102132, pp. 102132.

Fli1+ cells transcriptional analysis reveals an Lmo2-Prdm16 axis in angiogenesis
Matrone, G, Xia, B, Chen, K, Denvir, MA, Baker, AH & Cooke, JP 2021, , Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 31, e2008559118.

Induced endothelial cells from peripheral arterial disease patients and neonatal fibroblasts have comparable angiogenic properties
Hywood, JD, Sadeghipour, S, Clayton, ZE, Yuan, J, Stubbs, C, Wong, JWT, Cooke, JP & Patel, S 2021, , PLoS ONE, vol. 16, no. 8 August, e0255075.

Biomimetic and immunomodulatory therapeutics as an alternative to natural exosomes for vascular and cardiac applications
Villarreal-Leal, RA, Cooke, JP & Corradetti, B 2021, , Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 35, 102385, pp. 102385.

Mechanotransduction-on-chip: Vessel-chip model of endothelial YAP mechanobiology reveals matrix stiffness impedes shear response
Walther, BK, Rajeeva Pandian, NK, Gold, KA, Kiliç, ES, Sama, V, Gu, J, Gaharwar, AK, Guiseppi-Elie, A, Cooke, JP & Jain, A 2021, , Lab on a Chip, vol. 21, no. 9, pp. 1738-1751.

RNA therapeutics for cardiovascular disease
Boada, C, Sukhovershin, R, Pettigrew, R & Cooke, JP 2021, , Current Opinion in Cardiology, vol. 36, no. 3, pp. 256-263.

The Limitless Future of RNA Therapeutics
Damase, TR, Sukhovershin, R, Boada, C, Taraballi, F, Pettigrew, RI & Cooke, JP 2021, , Frontiers in Bioengineering and Biotechnology, vol. 9, 628137.

Biomimetic nano drug delivery carriers for treating cardiovascular diseases
Zinger, A, Cooke, JP & Taraballi, F 2021, , Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 33, 102360, pp. 102360.

Role of Endothelial and Mesenchymal Cell Transitions in Heart Failure and Recovery Thereafter
Wang, G, Cruz, AS, Youker, K, Marcos-Abdala, HG, Thandavarayan, RA, Cooke, JP, Torre-Amione, G, Chen, K & Bhimaraj, A 2021, , Frontiers in Genetics, vol. 11, 609262, pp. 609262.