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John P. Cooke, MD, PhD

Joseph C. “Rusty” Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research, Department of Cardiovascular Sciences
Professor of Cardiovascular Sciences, Academic Institute
Full Member, Research Institute
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 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 20,000 citations. He serves 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 nuclear reprogramming. 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 is now in Phase II 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, he has generated and characterized endothelial cells derived from human iPSCs, and explored their role in angiogenesis and vascular regeneration. Recent insights from the laboratory have clarified the role of innate immune signaling in nuclear reprogramming to pluripotency and therapeutic transdifferentiation for vascular disease.

Areas Of Expertise

Regenerative medicine Stem cell Vascular disease Endothelium
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

Rapamycin-Loaded Biomimetic Nanoparticles Reverse Vascular Inflammation
Boada, C, Zinger, A, Tsao, C, Zhao, P, Martinez, JO, Hartman, K, Naoi, T, Sukhoveshin, R, Sushnitha, M, Molinaro, R, Trachtenberg, BH, Cooke, JP & Tasciotti, E 2020, Circulation Research, vol. 126, no. 1, pp. 25-37.

AYAP modRNA reduces cardiac inflammation and hypertrophy in a murine ischemia-reperfusion model
Chen, J, Ma, Q, King, JS, Sun, Y, Xu, B, Zhang, X, Zohrabian, S, Guo, H, Cai, W, Li, G, Bruno, I, Cooke, JP, Wang, C, Kontaridis, M, Wang, DZ, Luo, H, Pu, WT & Lin, Z 2020, Life Science Alliance, vol. 3, no. 1, e201900424.

Endothelial senescence-associated secretory phenotype (SASP) is regulated by Makorin-1 ubiquitin E3 ligase
Kotla, S, Le, N-T, Vu, HT, Ko, KA, Gi, YJ, Thomas, TN, Giancursio, C, Lusis, AJ, Cooke, JP, Fujiwara, K & Abe, JI 2019, Metabolism: Clinical and Experimental, vol. 100, 153962.

Rapamycin-Loaded Leukosomes Reverse Vascular Inflammation
Boada, C, Zinger, A, Tsao, C, Zhao, P, MARTINEZ JONATHAN, O, Hartman, KA, Naoi, T, Sukhovershin, R, Sushnitha, M, Molinaro, R, Trachtenberg, BH, Cooke, JP & Tasciotti, E 2019, Circulation Research.

Dysfunction of iPSC-derived endothelial cells in human Hutchinson–Gilford progeria syndrome
Matrone, G, Amirthalingam Thandavarayan, R, Walther, BK, Meng, S, Mojiri, A & Cooke, JP 2019, Cell Cycle, vol. 18, no. 19, pp. 2495-2508.

Nuclear S-Nitrosylation Defines an Optimal Zone for Inducing Pluripotency
Chanda, PK, Meng, S, Lee, J, Leung, HE, Chen, K & Cooke, JP 2019, Circulation, vol. 140, no. 13, pp. 1081-1099.

Transient introduction of human telomerase mRNA improves hallmarks of progeria cells
Li, Y, Zhou, G, Bruno, IG, Zhang, N, Sho, S, Tedone, E, Lai, TP, Cooke, JP & Shay, JW 2019, Aging Cell, vol. 18, no. 4, e12979.

Cardiovascular Risk of Proton Pump Inhibitors
Ariel, H & Cooke, JP 2019, Methodist DeBakey cardiovascular journal, vol. 15, no. 3, pp. 214-219.

Dietary Supplements: Facts and Fallacies
Raizner, AE & Cooke, JP 2019, Methodist DeBakey cardiovascular journal, vol. 15, no. 3, pp. 169-170.

Endothelial senescence is induced by phosphorylation and nuclear export of telomeric repeat binding factor 2–interacting protein
Kotla, S, Vu, HT, Ko, KA, Wang, Y, Imanishi, M, Heo, KS, Fujii, Y, Thomas, TN, Gi, YJ, Mazhar, H, Paez-Mayorga, J, Shin, JH, Tao, Y, Giancursio, CJ, Medina, JLM, Taunton, J, Lusis, AJ, Cooke, JP, Fujiwara, K, Le, N-T & Abe, JI 2019, JCI Insight, vol. 4, no. 9, e124867.

Inflammation and Its Role in Regeneration and Repair
Cooke, JP 2019, Circulation Research, vol. 124, no. 8, pp. 1166-1168.

MAGI1 as a link between endothelial activation and ER stress drives atherosclerosis
Abe, J-I, Ko, KA, Kotla, S, Wang, Y, Paez-Mayorga, J, Shin, IJ, Imanishi, M, Vu, HT, Tao, Y, Leiva-Juarez, MM, Thomas, TN, Medina, JL, Won, JH, Fujii, Y, Giancursio, CJ, McBeath, E, Shin, J-H, Guzman, L, Abe, RJ, Taunton, J, Mochizuki, N, Faubion, W, Cooke, JP, Fujiwara, K, Evans, SE & Le, N-T 2019, JCI Insight, vol. 4, no. 7.

AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate
Gu, Q, Yang, X, Lv, J, Zhang, J, Xia, B, Kim, JD, Wang, R, Xiong, F, Meng, S, Clements, TP, Tandon, B, Wagner, DS, Diaz, MF, Wenzel, PL, Miller, YI, Traver, D, Cooke, JP, Li, W, Zon, LI, Chen, K, Bai, Y & Fang, L 2019, Science, pp. eaav1749.

Convergences of Life Sciences and Engineering in Understanding and Treating Heart Failure
Berry, JL, Zhu, W, Tang, YL, Krishnamurthy, P, Ge, Y, Cooke, JP, Chen, Y, Garry, DJ, Yang, HT, Rajasekaran, NS, Koch, WJ, Li, S, Domae, K, Qin, G, Cheng, K, Kamp, TJ, Ye, L, Hu, S, Ogle, BM, Rogers, JM, Abel, ED, Davis, ME, Prabhu, SD, Liao, R, Pu, WT, Wang, Y, Ping, P, Bursac, N, Vunjak-Novakovic, G, Wu, JC, Bolli, R, Menasché, P & Zhang, J 2019, Circulation Research, vol. 124, no. 1, pp. 161-169.

Glycolytic Switch Is Required for Transdifferentiation to Endothelial Lineage
Lai, L, Reineke, EL, Hamilton, DJ & Cooke, JP 2019, Circulation, vol. 139, no. 1, pp. 119-133.,

Asymmetric dimethylarginine predicts impaired epicardial coronary vasomotion in patients with angina in the absence of obstructive coronary artery disease
Parikh, RV, Pargaonkar, V, Ball, RL, Kobayashi, Y, Kimura, T, Yeung, AC, Cooke, JP & Tremmel, JA 2019, International Journal of Cardiology.

TBX20 Regulates Angiogenesis Through the Prokineticin 2-Prokineticin Receptor 1 Pathway
Meng, S, Gu, Q, Yang, X, Lv, J, Owusu, I, Matrone, G, Chen, K, Cooke, JP & Fang, L 2018, Circulation, vol. 138, no. 9, pp. 913-928.

Novel Markers for Adverse Events in Atrial Fibrillation
Cooke, JP & Sukhovershin, R 2018, Journal of the American College of Cardiology, vol. 72, no. 7, pp. 734-737.

Harnessing and Optimizing the Interplay between Immunotherapy and Radiotherapy to Improve Survival Outcomes
Mujoo, K, Hunt, CR, Pandita, RK, Ferrari, M, Krishnan, S, Cooke, JP, Hahn, S & Pandita, TK 2018, Molecular Cancer Research, vol. 16, no. 8, pp. 1209-1214.

Cardiomyocyte Maturation Requires TLR3 Activated Nuclear Factor Kappa B
Hodgkinson, CP, Pratt, RE, Kirste, I, Dal-Pra, S, Cooke, JP & Dzau, VJ 2018, Stem Cells, vol. 36, no. 8, pp. 1198-1209.

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