NIH Biosketch available OnlineJohn Cooke, MD, PhD
- Professor, Medicine - Cardiovascular Medicine
- Member, Bio-X
Contact Information
- Clinical Offices
Cardiovascular Medicine Clinic 300 Pasteur Dr A260 MC 5319 Stanford, CA 94305-2200 Telephone Work (650) 723-6459 Fax (650) 723-8392
- Academic Offices
Personal Information Email John.Cooke@stanford.edu Tel (650) 723-6141, (650) 725-3778Administrative Contact Scott Reiff Email sreiff@stanford.eduNot for medical emergencies or patient use
Clinical Focus
- Cardiology (Heart)
- Cardiology (Heart), Preventive
- Cardiovascular Disease
- Vascular Medicine
Administrative Appointments
- Associate Director (Education and Training), Stanford Cardiovascular Institute , (2007– present )
- Director, Training program in Vascular Medicine and Biology , (1991– 2007 )
Honors and Awards
- Master of the Society for Vascular Medicine, Society for Vascular Medicine (2009)
- Established Investigator Award, American Heart Association (1995)
- Teaching Award, Dept of Medicine (2001)
- "Best Doctors in the Bay Area", San Francisco Magazine (2003,2005)
- President, Society for Vascular Medicine (2005-2007)
Professional Education
- Board Certification: Cardiovascular Disease, American Board of Internal Medicine (1987)
- Mayo Graduate School of Medicine (1987) MN
- Mayo Graduate School of Medicine (1985) MN
- Board Certification: Internal Medicine, American Board of Internal Medicine (1983)
- Mayo Clinic (1983) MN
- Mayo Clinic (1981) MN
- Wayne State University School of Medicine (1980) MI
- PhD, Mayo Graduate School of Medicine Physiology (1985)
- MD, WSU School of Medicine Medicine (1980)
Postdoctoral Advisees
Graduate & Fellowship Program Affiliations
Web Site Links
Industry Relationships
Stanford is committed to ethical and transparent interactions with our industry partners. It is our policy to disclose payments of $5,000 or more, equity valued at $5,000 or more in a publicly traded company, or any equity in a privately held company, to physicians and scientists employed by Stanford University from companies or other commercial entities with which they interact as part of their professional activities.
- Consulting: CoMentis, Vermillion
- Royalty Payments: CoMentis
- Equity: CoMentis, Navitas
Research Interests
Dr. Cooke is Professor of Medicine and Associate Director (Education and Training)of the Stanford Cardiovascular Institute. His research group performs translational work in vascular regeneration from molecule to man. The goal is to transfer basic research insights into clinical trials using a vertically integrated approach with an array of biochemical and molecular tools, cellular and animal models, and clinical research techniques. Our mission is to to build new blood vessels, reverse vascular senescence, and to improve vascular health.
Our clinical research is focused on patients with peripheral arterial disease (PAD). We are testing new therapies for angiogenesis and vascular regeneration including novel small molecules and cell therapy. The usual endpoints of our trials are functional capacity (eg. peak walking time), relief of ischemic pain or wound healing. Ongoing trials include gene and cell therapy for enhancing angiogenesis; as wel as a small molecule for increasing oxygen diffusion.
The basic research is focused on induced pluripotential stem cells (iPSCs) for vascular regeneration. We are developing cell-permeant proteins and new chemical entities for nuclear reprogramming, and for differentiation of iPSCs into endothelial cells. Human iPSC-derived endothelial cells are currently being tested in our murine model of PAD. Studies underway include genetic, epigenetic, mitochondrial, and functional characterization of human iPSCs derived from viral versus protein-based strategies. We anticipate that cell permeant peptides will avoid the concerns raised by DNA-based approaches (eg. integration of foreign DNA into the host chromosome), and will provide more control over dosing and duration of action of the reprogramming factors. We are also interested to discover new determinants of endothelial lineage that may enhance the yield of ECs derived from iPSCs. It will be important to determine if iPSC-derived ECs from patients with PAD have normal function, and can incorporate into the host microvasculature and enhance perfusion. Ultimately, we intend to develop clinical grade iPSC-ECs for vascular therapy, and to conduct the first trials of iPSC-EC in patients with PAD.
We have a long-standing interest in two different pathways regulating endothelial function. Endothelium derived nitric oxide synthase(NOS) plays a critical role in EC survival, proliferation, and angiogenesis. There is an endogenous competitive inhibitor of the NO synthase pathway called ADMA (asymmetric dimethylarginine). We find that this molecule is elevated in disorders associated with endothelial dysfunction, and plays a significant role in causing vascular disease. ADMA becomes elevated in people with hypercholesterolemia, diabetes, and other vascular disorders. We find that oxidative stress impairs the activity of the enzyme (DDAH) that degrades ADMA. ADMA accumulates and blocks NO synthesis. Overexpression of DDAH (in our transgenic mouse or in endothelial cell culture) can reduce ADMA levels and increase NO synthesis, with significant consequences on vascular homeostasis and angiogenesis(Jacobi et al Circulation 2005).
More recently we have serendipitously discovered a new pathway modulating angiogenesis (Heeschen et al, Nature Medicine 2001). Nicotinic acetylcholine receptors on endothelial cells are upregulated with hypoxia, and when stimulated (by the endogenous transmitter acetylcholine), these receptors mediate endothelial tube formation in vitro, and angiogenesis in vivo. Of great interest, this pathway is hijacked by nicotine. Thus nicotine can pathologically activate tumor angiogenesis and tumor growth. Nicotine can also stimulate the neovascularization of atherosclerotic plaque, leading to its further growth. These findings suggest a new paradigm for tobacco-related diseases, and provide for a new platform for therapeutic manipulations of the pathway.
Clinical Trials
Publications
- J Cell Biochem. 2009; (2): 433-46
- J Vis Exp. 2009; (23)
- Arterioscler Thromb Vasc Biol. 2008; (4): 692-7
- Trends Cardiovasc Med. 2008; (7): 247-53
- Arterioscler Thromb Vasc Biol. 2007; (1): 106-12
- Circulation. 2007; (12): 1396-403
- Arterioscler Thromb Vasc Biol. 2007; (10): 2068-78
- J Am Coll Cardiol. 2007; (10): 1099-105
- Circulation. 2007; (11 Suppl): I46-54
- J Am Coll Cardiol. 2006; (12): 2553-60
- Circulation. 2005; (11): 1431-8
- Circulation. 2005; (11): 1549-56
- Gene Ther. 2004; (3): 302-9
- Circulation. 2004; (15): 1813-8
- Circulation. 2003; (24): 3042-7
- Cancer Cell. 2003; (3): 191-6
- Circulation. 2002; (8): 987-92
- J Clin Invest. 2002; (4): 527-36
- Nat Med. 2001; (7): 833-9
- Biotechnol Bioeng. 2009; (6): 1047-58
- Vasc Med. 2009;
- Vasc Med. 2009; (3): 249-57
- J Psychiatr Res. 2009; (16): 1246-52
- J Vis Exp. 2009; (23)
- J Cell Biol. 2009; (1): 83-99
- Kidney Blood Press Res. 2008; (4): 259-67
- Transplantation. 2008; (6): 827-33
- Stroke. 2008; (1): 180-4
- Life Sci. 2007; (24-25): 2347-51
- Clin Chem. 2007; (2): 161-3
- Transplantation. 2007; (6): 700-5
- J Clin Microbiol. 2007; (6): 1804-10
- Neurosci Lett. 2007; (2): 201-4
- J Urol. 2007; (6): 2342-6
- Circulation. 2007; (2): 188-95
- Circ Res. 2007; (4): 581-9
- Psychosom Med. 2006 Jul-Aug; (4): 538-46
- Nephrol Dial Transplant. 2006; (9): 2446-51
- Stroke. 2006; (8): 2024-9
- Stroke. 2006;
- Vasc Med. 2006; (3): 177-80
- Vasc Med. 2006; (3): 155-63
- Circulation. 2006; (15): 1608-15
- FASEB J. 2006; (14): 2657-9
- Int Angiol. 2006; (4): 361-9
- Transplantation. 2006; (3): 398-405
- Vasc Med. 2005; (4): 275-83
- Vasc Med. 2005; (1): 7-14
- Vasc Med. 2005; S11-7
- Vasc Med. 2005; S35-43
- Vasc Med. 2005; (4): 293-307
- Can J Cardiol. 2004; 7B-15B
- Vasc Med. 2004; (1): 26-30
- Ann Med. 2004; (1): 33-40
- Circulation. 2004; (10): 1314-9
- Circulation. 2004; (4): 500-5
- Circulation. 2004; (16): 2424-9
- J Sep Sci. 2004; (17-18): 1483-90
- J Am Coll Cardiol. 2003; (3): 489-96
- Am J Physiol Heart Circ Physiol. 2003; (2): H535-40
- Arterioscler Thromb Vasc Biol. 2003; (4): 567-75
- Atherosclerosis. 2003; (2): 333-41
- Circulation. 2003; (12): 1420-1
- Atheroscler Suppl. 2003; (4): 53-60
- Proc Natl Acad Sci U S A. 2003; (3): 768-70
- Circulation. 2003; (8): 933-8
- Am J Cardiol. 2002; (4): 363-7
- Circulation. 2002; (6): 739-45
- JAMA. 2002; (11): 1420-6
- Metabolism. 2002; (7): 843-6
- Am J Pathol. 2002; (1): 97-104
- Arterioscler Thromb Vasc Biol. 2002; (11): 1817-23
- Circ J. 2002; (12): 1155-60
- Prev Cardiol. 2001; (1): 28-37
- Vasc Med. 2001; (3): 133-8
- J Appl Physiol. 2001; (3): 933-8
- Curr Atheroscler Rep. 2001; (3): 252-9
- Circ Res. 2001; (9): 793-8
- Am J Cardiol. 2001; (10): 1201-3
- Circulation. 2001; (21): 2569-75
- J Am Coll Cardiol. 2000; (7): 2287-95
- Vasc Med. 2000; (3): 147-58
- Circulation. 2000; (21): 2629-35
- Circulation. 2000; (19): 2322-4
- Am J Med. 2000; (4): 296-300
- Prev Cardiol. 2000; (4): 172-177
- Arterioscler Thromb Vasc Biol. 2000; (4): 1040-6
- J Am Coll Cardiol. 2000; (6): 1403-10
- Arterioscler Thromb Vasc Biol. 2000; (9): 2032-7
- Circulation. 2000; (12): 1414-9
- Vasc Med. 2000; (1): 49-53
- Circulation. 1999; (9): 1236-41
- J Cardiol. 1999; (2): 105-6
- Am J Physiol. 1999; (4 Pt 2): H1346-54
- Vasc Med. 1999; (1): 27-32
- Circulation. 1999; (17): 1830-5
- Vasc Med. 1999; (2): 89-91
- Circulation. 1999; (9): 940-3
- J Am Coll Cardiol. 1999; (4): 1201-7
- Circulation. 1999; (24): 3092-5
- Curr Opin Nephrol Hypertens. 1998; (1): 63-70
- West J Med. 1998; (4): 255-60
- Arterioscler Thromb Vasc Biol. 1998; (6): 947-53
- Vasc Med. 1998; (1): 29-31
- Circulation. 1998; (4): 369-74
- Circulation. 1998; (18): 1842-7
- J Investig Med. 1998; (8): 377-80
- Am J Cardiol. 1998; (10A): 43S-46S
- Adv Intern Med. 1998; 253-77
- J Cardiovasc Pharmacol. 1998; S48-53
- Vasc Med. 1997; (3): 227-30
- Vasc Med. 1997; (1): 1-7
- J Exp Med. 1997; (12): 2069-77
- Annu Rev Med. 1997; 489-509
- J Am Coll Cardiol. 1997; (3): 479-85
- Circulation. 1997; (7): 1863-9
- Circulation. 1997; (3): 934-40
- Diabetes Care. 1997; (9): 1462-5
- Blood. 1997; (9): 3587-94
- Clin Cardiol. 1997; (11 Suppl 2): II-45-51
- Arterioscler Thromb Vasc Biol. 1997; (12): 3557-64
- J Am Coll Cardiol. 1996; (7): 1652-60
- Vasc Med. 1996; (1): 19-23
- Vasc Med. 1996; (4): 247-50
- Vasc Med. 1996; (3): 173-9
- Arterioscler Thromb Vasc Biol. 1996; (1): 44-50
- Circulation. 1996; (7): 1682-9
- West J Med. 1996; (5): 419-24
- J Vasc Surg. 1996; (4): 596-605
- Circulation. 1996; (4): 720-9
- J Am Coll Cardiol. 1996; (6): 1573-9
- Proc Natl Acad Sci U S A. 1995; (10): 4502-6
- JAMA. 1995; (24): 1919-25
- Surg Clin North Am. 1995; (4): 569-79
- Circulation. 1995; (12): 3513-9
- J Cardiovasc Pharmacol. 1995; (5): 710-6
- Proc Natl Acad Sci U S A. 1995; (4): 1137-41
- J Clin Invest. 1995; (3): 1363-9
- J Am Coll Cardiol. 1994; (2): 452-8
- J Gerontol. 1994; (5): B191-6
- Circulation. 1994; (5): 2176-82
- Circulation. 1994; (4): 1615-23
- Arterioscler Thromb. 1994; (10): 1529-33
- Circulation. 1994; (2): 777-84
- Circulation. 1993; (3): 705-19
- Circulation. 1993; (1): 193-7
- Rev Port Cardiol. 1992; (10): 889-92
- J Clin Invest. 1992; (3): 1168-72
- Basic Res Cardiol. 1991; 173-81
- J Clin Invest. 1991; (5): 1663-71