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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
Chair, Department of Cardiovascular Sciences
Professor of Cardiovascular Sciences, Academic Institute
Full Member, Research Institute
Director, Center for Cardiovascular Regeneration
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

Machine learning uncovers cell identity regulator by histone code
Xia, B, Zhao, D, Wang, G, Zhang, M, Lv, J, Tomoiaga, AS, Li, Y, Wang, X, Meng, S, Cooke, JP, Cao, Q, Zhang, L & Chen, K 2020, Nature Communications, vol. 11, no. 1, 2696. https://doi.org/10.1038/s41467-020-16539-4

TADsplimer reveals splits and mergers of topologically associating domains for epigenetic regulation of transcription
Wang, G, Meng, Q, Xia, B, Zhang, S, Lv, J, Zhao, D, Li, Y, Wang, X, Zhang, L, Cooke, JP, Cao, Q & Chen, K 2020, Genome Biology, vol. 21, no. 1, 84. https://doi.org/10.1186/s13059-020-01992-7

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. https://doi.org/10.1161/CIRCRESAHA.119.315185

Nanobiosensing with graphene and carbon quantum dots: Recent advances
Walther, BK, Dinu, CZ, Guldi, DM, Sergeyev, VG, Creager, SE, Cooke, JP & Guiseppi-Elie, A 2020, Materials Today. https://doi.org/10.1016/j.mattod.2020.04.008

Vascular Regeneration in Peripheral Artery Disease
Meng, S & Cooke, JP 2020, Arteriosclerosis, Thrombosis, and Vascular Biology, pp. 1627-1634. https://doi.org/10.1161/ATVBAHA.120.312862

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. https://doi.org/10.26508/lsa.201900424

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. https://doi.org/10.1016/j.metabol.2019.153962

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. https://doi.org/10.1080/15384101.2019.1651587

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. https://doi.org/10.1161/CIRCULATIONAHA.119.042371

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. https://doi.org/10.1111/acel.12979

Cardiovascular Risk of Proton Pump Inhibitors
Ariel, H & Cooke, JP 2019, Methodist DeBakey cardiovascular journal, vol. 15, no. 3, pp. 214-219. https://doi.org/10.14797/mdcj-15-3-214

Dietary Supplements: Facts and Fallacies
Raizner, AE & Cooke, JP 2019, Methodist DeBakey cardiovascular journal, vol. 15, no. 3, pp. 169-170. https://doi.org/10.14797/mdcj-15-3-169

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. https://doi.org/10.1172/jci.insight.124867

Inflammation and Its Role in Regeneration and Repair
Cooke, JP 2019, Circulation Research, vol. 124, no. 8, pp. 1166-1168. https://doi.org/10.1161/CIRCRESAHA.118.314669

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. https://doi.org/10.1172/jci.insight.125570

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. https://doi.org/10.1126/science.aav1749

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. https://doi.org/10.1161/CIRCRESAHA.118.314216

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. https://doi.org/10.1161/CIRCULATIONAHA.118.035741, https://doi.org/10.1161/CIRCULATIONAHA.118.035741

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. https://doi.org/10.1016/j.ijcard.2019.07.062