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


Biography

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
Publications

Transflammation in tissue regeneration and response to injury: How cell-autonomous inflammatory signaling mediates cell plasticity
Cooke, JP & Lai, L 2023, , Advanced Drug Delivery Reviews, vol. 203, 115118. https://doi.org/10.1016/j.addr.2023.115118

Coronary microvascular health in symptomatic patients with prior COVID-19 infection: an updated analysis
Ahmed, AI, Al Rifai, M, Alahdab, F, Saad, JM, Han, Y, Alfawara, MS, Nayfeh, M, Malahfji, M, Nabi, F, Mahmarian, JJ, Cooke, JP, Zoghbi, WA & Al-Mallah, MH 2023, , European Heart Journal Cardiovascular Imaging, vol. 24, no. 11, pp. 1544-1554. https://doi.org/10.1093/ehjci/jead118

Disrupted stiffness ratio alters nuclear mechanosensing
Walther, BK, Sears, AP, Mojiri, A, Avazmohammadi, R, Gu, J, Chumakova, OV, Rajeeva Pandian, NK, Dominic, A, Martiel, JL, Yazdani, SK, Cooke, JP, Ohayon, J & Pettigrew, RI 2023, , Matter, vol. 6, no. 10, pp. 3608-3630. https://doi.org/10.1016/j.matt.2023.08.010

Reassessing withholding of statins during Paxlovid therapy: Is it worth risking loss of the pleiotropic effects of statins and cardiovascular protection?
Ariel, H, Ricupero, A & Cooke, JP 2023, , American Journal of Health-System Pharmacy, vol. 80, no. 18, pp. 1204-1205. https://doi.org/10.1093/ajhp/zxad135

A2AR-mediated lymphangiogenesis via VEGFR2 signaling prevents salt-sensitive hypertension
Zhuang, T, Lei, Y, Chang, JJ, Zhou, YP, Li, Y, Li, YX, Yang, YF, Chen, MH, Meng, T, Fu, SM, Huang, LH, Cheang, WS, Cooke, JP, Dong, ZH, Bai, YN & Ruan, CC 2023, , European heart journal, vol. 44, no. 29, pp. 2730-2742. https://doi.org/10.1093/eurheartj/ehad377

An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis
Abe, J-I, Imanishi, M, Li, S, Zhang, A, Ko, KA, Samanthapudi, VSK, Lee, L-L, Bojorges, AP, Gi, YJ, Hobbs, BP, Deswal, A, Herrmann, J, Lin, SH, Chini, EN, Shen, YH, Schadler, KL, Nguyen, T-H-M, Gupte, AA, Reyes-Gibby, C, Yeung, S-CJ, Abe, RJ, Olmsted-Davis, EA, Krishnan, S, Dantzer, R, Palaskas, NL, Cooke, JP, Pownall, HJ, Yoshimoto, M, Fujiwara, K, Hamilton, DJ, Burks, JK, Wang, G, Le, N-T & Kotla, S 2023, , Circulation Research, vol. 133, no. 1, pp. 25-44. https://doi.org/10.1161/CIRCRESAHA.122.322017

Coronary microvascular health in symptomatic patients with prior COVID-19 infection: an updated analysis
Ahmed, AI, Al Rifai, M, Alahdab, F, Saad, JM, Han, Y, Alfawara, MS, Nayfeh, M, Malahfji, M, Nabi, F, Mahmarian, JJ, Cooke, JP, Zoghbi, WA & Al-Mallah, MH 2023, , European Heart Journal Cardiovascular Imaging, vol. 24, no. 11, pp. 1544-1554. https://doi.org/10.1093/ehjci/jead118

Publisher Correction: Epigenetic landscape reveals MECOM as an endothelial lineage regulator
Lv, J, Meng, S, Gu, Q, Zheng, R, Gao, X, Kim, JD, Chen, M, Xia, B, Zuo, Y, Zhu, S, Zhao, D, Li, Y, Wang, G, Wang, X, Meng, Q, Cao, Q, Cooke, JP, Fang, L, Chen, K & Zhang, L 2023, , Nature Communications, vol. 14, no. 1, 2842, pp. 2842. https://doi.org/10.1038/s41467-023-38708-x

Design and rationale of re-energize fontan: Randomized exercise intervention designed to maximize fitness in fontan patients
Selamet Tierney, ES, Palaniappan, L, Leonard, M, Long, J, Myers, J, Dávila, T, Lui, MC, Kogan, F, Olson, I, Punn, R, Desai, M, Schneider, LM, Wang, CH, Cooke, JP & Bernstein, D 2023, , American Heart Journal, vol. 259, pp. 68-78. https://doi.org/10.1016/j.ahj.2023.02.006

Epigenetic landscape reveals MECOM as an endothelial lineage regulator
Lv, J, Meng, S, Gu, Q, Zheng, R, Gao, X, Kim, JD, Chen, M, Xia, B, Zuo, Y, Zhu, S, Zhao, D, Li, Y, Wang, G, Wang, X, Meng, Q, Cao, Q, Cooke, JP, Fang, L, Chen, K & Zhang, L 2023, , Nature Communications, vol. 14, no. 1, 2390, pp. 2390. https://doi.org/10.1038/s41467-023-38002-w

A relay velocity model infers cell-dependent RNA velocity
Li, S, Zhang, P, Chen, W, Ye, L, Brannan, KW, Le, NT, Abe, JI, Cooke, JP & Wang, G 2023, , Nature Biotechnology, vol. 42, no. 1, pp. 99-108. https://doi.org/10.1038/s41587-023-01728-5

Long noncoding RNA LEENE promotes angiogenesis and ischemic recovery in diabetes models
Tang, X, Luo, Y, Yuan, D, Calandrelli, R, Malhi, NK, Sriram, K, Miao, Y, Lou, CH, Tsark, W, Tapia, A, Chen, AT, Zhang, G, Roeth, D, Kalkum, M, Wang, ZV, Chien, S, Natarajan, R, Cooke, JP, Zhong, S & Chen, ZB 2023, , Journal of Clinical Investigation, vol. 133, no. 3, e161759. https://doi.org/10.1172/JCI161759

Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors
Banerjee, P, Rosales, JE, Chau, K, Nguyen, MTH, Kotla, S, Lin, SH, Deswal, A, Dantzer, R, Olmsted-Davis, EA, Nguyen, H, Wang, G, Cooke, JP, Abe, JI & Le, NT 2023, , Frontiers in Cardiovascular Medicine, vol. 10, 1186679, pp. 1186679. https://doi.org/10.3389/fcvm.2023.1186679

Role of angiogenic transdifferentiation in vascular recovery
Cooke, JP & Lai, L 2023, , Frontiers in Cardiovascular Medicine, vol. 10, 1155835, pp. 1155835. https://doi.org/10.3389/fcvm.2023.1155835

Electrically stimulated gene expression under exogenously applied electric fields
Abasi, S, Jain, A, Cooke, JP & Guiseppi-Elie, A 2023, , Frontiers in Molecular Biosciences, vol. 10, 1161191, pp. 1161191. https://doi.org/10.3389/fmolb.2023.1161191

Telomerase mRNA Enhances Human Skin Engraftment for Wound Healing
Chang, DF, Court, KA, Holgate, R, Davis, EA, Bush, KA, Quick, AP, Spiegel, AJ, Rahimi, M, Cooke, JP & Godin, B 2023, , Advanced Healthcare Materials, vol. 13, no. 2, 2302029, pp. e2302029. https://doi.org/10.1002/adhm.202302029

Endothelial activation and fibrotic changes are impeded by laminar flow-induced CHK1-SENP2 activity through mechanisms distinct from endothelial-to-mesenchymal cell transition
Nguyen, MTH, Imanishi, M, Li, S, Chau, K, Banerjee, P, Velatooru, LR, Ko, KA, Samanthapudi, VSK, Gi, YJ, Lee, LL, Abe, RJ, McBeath, E, Deswal, A, Lin, SH, Palaskas, NL, Dantzer, R, Fujiwara, K, Borchardt, MK, Turcios, EB, Olmsted-Davis, EA, Kotla, S, Cooke, JP, Wang, G, Abe, JI & Le, NT 2023, , Frontiers in Cardiovascular Medicine, vol. 10, 1187490, pp. 1187490. https://doi.org/10.3389/fcvm.2023.1187490

Premature senescence and cardiovascular disease following cancer treatments: mechanistic insights
Jain, A, Casanova, D, Padilla, AV, Paniagua Bojorges, A, Kotla, S, Ko, KA, Samanthapudi, VSK, Chau, K, Nguyen, MTH, Wen, J, Hernandez Gonzalez, SL, Rodgers, SP, Olmsted-Davis, EA, Hamilton, DJ, Reyes-Gibby, C, Yeung, SCJ, Cooke, JP, Herrmann, J, Chini, EN, Xu, X, Yusuf, SW, Yoshimoto, M, Lorenzi, PL, Hobbs, B, Krishnan, S, Koutroumpakis, E, Palaskas, NL, Wang, G, Deswal, A, Lin, SH, Abe, JI & Le, NT 2023, , Frontiers in Cardiovascular Medicine, vol. 10, 1212174, pp. 1212174. https://doi.org/10.3389/fcvm.2023.1212174

Is Cardiovascular Regeneration Possible?
Cooke, JP 2023, , Methodist DeBakey cardiovascular journal, vol. 19, no. 5, pp. 1-4. https://doi.org/10.14797/mdcvj.1307

Mechanisms of Atherosclerosis in Peripheral Arterial Diseases
Cooke, JP 2023, . in Peripheral Arterial Disease Handbook. CRC Press, pp. 3-20. https://doi.org/10.1201/9780429191497-2