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Program Director/Principle Investigator (Last, First, Middle):
Cheresh, David A.
BIOGRAPHICAL SKETCH
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NAME
POSITION TITLE
Cheresh, David A.
Professor
eRA COMMONS USER NAME (credential, e.g., agency login)
CHERESH
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and
residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
University of Michigan, Ann Arbor, MI
University of Miami, Miami, FL
University of Miami, Miami, FL
B.S.
M.S.
Ph.D.
1975
1978
1982
Biology
Microbiology
Immunology
A. Personal Statement
A major goal of our research is to understand the molecular of pathological neovascularization. We
have begun to understand how growth factors such as VEGF and its receptor(s) as well as integrins
impact the process of neovascularization. We are interested in how growth factors and integrins
regulate vascular cell signals that enable blood vessel growth and stabilization. My research efforts
have helped to delineate how these processes are regulated at the molecular level. These studies
have lead to the development of integrin antagonists as novel therapeutics for cancer treatment that
function to suppress the growth of angiogenic blood vessels. Two drugs that have developed from our
work include Vitaxin (Abegrin) a humanized monoclonal antibody that targets avb3 and Cilengitide a
cyclic peptide antagonist of integrins avb3 and avb5. Both of these drugs have show clinical activity
in cancer patients in Phase II trials and are now being tested in Phase III trials. It is likely that these
efforts will help to define the molecular basis of drugs such as Vitaxin and Cilengitide which are
beginning to show promise for patients with metastatic disease. A second area of focus involves the
development of tumor vascular targeted nanoparticles. We have developed strategies to target
drugs, genes and imaging molecules to neovascular tissue. This has allowed us to both image or
therapeutically treat the growth of tumors.
B. Positions and Honors
Positions and Employment
1985-1989
Assistant Professor, Dept. of Immunology, The Scripps Research Institute, La Jolla, CA.
1989-1996
Associate Professor, Dept. of Immunology, The Scripps Research Institute, La Jolla, CA.
1996-2005
Professor, Depts. of IMM & Vascular Biology, The Scripps Research Institute, La Jolla, CA.
2005-present Professor, Department of Pathology, University of California, San Diego, La Jolla, CA.
2005-present Professor, Assoc. Director for Translational Res., Moores UCSD Cancer Center, La Jolla, CA.
2006-present Vice Chair for Research, Dept. of Pathology, UCSD, La Jolla, CA.
Other Experience and Professional Memberships
1987-present Member, The American Society for Cell Biology
1994-present Member, American Association for the Advancement of Science
1996-present Scientific Advisory Board member, North American Vascular Biology Organization
1997
Myron Karon Memorial Lecturer, Children’s Hospital, Los Angeles
1997
15th Hans Lindner Memorial Lecturer, Weizmann Institute of Science, Rehovot, Israel
1998-present Member, American Association for Cancer Research
1998
McGill University Visiting Professor in Oncology, Montreal, Quebec, Canada
1998
Robert Bear Lecturer, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
2000
Chairman, Gordon Research Conference on Vascular Biology
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Cheresh, David A.
2001
Chairman, Gordon Research Conference on Angiogenesis and Microcirculation
2002
Organizer and Chairman Keystone Symp. on Biological Response to the Extracellular Matrix
2004-present Member, The American Society for Hematology
2004
Visiting Professorship, University New Mexico Cancer Center
2007
Organizer and Chairman Keystone Symp. ”Host Cell Interaction and Response to Cancer Cell”
2008
Organizer and Chairman, 4th Annual Translational Onc. Symp. Moores Cancer Ctr, La Jolla, CA
2009
Organizer and Chairman, 21st Annual Usha Mahajani Symposium, La Jolla, CA
2010
Invited speaker, Gordon Research Conference, University of New England, Biddeford, ME
2010
Invited speaker, 16th International Vascular Biology Meeting, UCLA, Los Angeles, CA
Program Director/Principle Investigator (Last, First, Middle):
Honors
1999
1999
2002
2003
2003
2005
2006
2007
2007
2007
2007
2009
2010
2010
Recipient, 75th Anniversary Spirit of Scripps Award, La Jolla, California
Recipient, NIH MERIT award, CA50286
Keynote Spkr, Society Biological Therapy Understanding Angiogenesis/Molecular Mechanisms
Keynote Spkr, Cold Spring Harbor Lab “Vector Targeting Strategies for Therapeutic Gene Del.
Keynote Spkr, Medical Univ. SC, Hollings Cancer Center Research Symposium
Basic Science Lecture Award, American Society of Cytopathology 53rd Annual Scientific Mtg
Elkin Distinguished Lecture, Emory University, Atlanta, Georgia
Davis Distinguished Lecturer, Cardiovascular Day 2007, University of Missouri, St. Louis, MO
Featured Speaker, Sidney Kimmel Cancer Center symposium. Coronado, CA
Highlight Lecture at Vasculata 2007, Chapel Hill, NC
Keynote Lecture, 3rd Annual Meeting of the American Academy of Nanomedicine, La Jolla, CA
Recipient, NIH MERIT award, CA50286
Recipient, Paget-Ewing award of the Metastasis Research Society and AACR Meeting
Keynote Lecture, 4th Mayo Clinic Angiogenesis Symposium, Mackinac Island, MI
C. Selected Peer-reviewed Publications (Selected from 214 peer-reviewed publications)
Recent publications of importance to the field (in chronological order)
1. Hood, J.D, Bednarski, M, Frausto, R, Guccione, S, Reisfeld, R.A, Xiang, R. & Cheresh D.A. Tumor
regression by targeted gene delivery to the neovasculature. Science 2002; 296:2404-7.
2. Alavi, A, Hood, J.D, Frausto, R, Stupack, D.G. & Cheresh D.A. Role of Raf in vascular protection from
distinct apoptotic stimuli. Science 2003; 301:94-6.
3. Hood, J.D, Frausto, R, Kiosses, W.B, Schwartz, M.A. & Cheresh D.A. Differential v-integrin-mediated
Ras-ERK signaling during two pathways of angiogenesis. J Cell Biol 2003; 162(5): 933-43.
PMCID:PMC2172815.
4. Weis, S.M. & Cheresh D.A. Pathophysiological consequences of VEGF-induced vascular permeability.
Nature 2005; 437:497-504.
5. Stupack, D.G, Teitz, T, Potter, M, Mikolon, D, Kidd, V.J, Lahti, J.M. & Cheresh D.A. Potentiation of
neuroblastoma metastasis by loss of caspase 8. Nature 2006; 439:95-9.
6. Alavi, A.S, Acevedo, L, Min, W. & Cheresh D.A. Chemoresistance of endothelial cells induced by bFGF
depends on Raf-1-mediated inhibition of the pro-apoptotic kinase, ASK1. Cancer Res 2007; 67:2766-72.
7. Murphy, E.A, Majeti, B.K, Barnes, L, Makale, M, Weis, S.M, Wrasidlo, W. & Cheresh D.A. Nanoparticlemediated drug delivery to tumor vasculature suppresses metastasis. PNAS 2008; 105:9343-8.
PMCID2453735.
8. Stockmann, C, Doedens, A, Weidemann, A, Zhang, N, Takeda, N, Greenberg, J.I, Cheresh D.A. and
Johnson, R.S. Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis.
Nature 2008; 456: 814-9.
9. Greenberg, J.I, Shields, D.J, Barillas, S.G, Acevedo, L.M, Murphy, E, Huang, J, Scheppke, E, Stockmann,
C, Johnson, R.S, Angle, N. & Cheresh D.A. A role for VEGF as a negative regulator of pericyte function
and vessel maturation. Nature 2008; 456: 809-13. PMCID2605188.
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Program Director/Principle Investigator (Last, First, Middle):
Cheresh, David A.
10. Ricono, J.M, Huang, M, Barnes, L.A, Lau, S.K, Weis, S.M, Schlaepfer, D.D, Hanks, S.K. & Cheresh D.A.
Specific crosstalk between EGFR and integrin αvβ5 promotes carcinoma cell invasion and metastasis. Can
Res 2009; 69(4): 1383-91. PMCID2741736.
11. Desgrosellier, J.S, Barnes, L.A, Shields, D.J, Huang, M, Lau, S.K, Prévost, N, Tarin, D, Shattil, S.J. and
Cheresh D.A. Integrin avb3/c-src “Oncogenic Unit” Promotes Anchorage-independence and Tumor
Progression. Nature Medicine 2009; 15:1163-1169. PMCID2759406
12. Desgrosellier, J.S. & Cheresh, D.A. Integrins in Cancer: Biological Implications and Therapeutic
Opportunities. Nat Rev Cancer 2010 Jan; 10(1):9-22. PMCID-in process.
13. Shields, D.J, Niessen, S, Murphy, E, Mielgo, A, Desgrosellier, J.S, Lau, S.K, Barnes, L.A, Lesperance, J,
Bouvet, M, Tarin, D, Cravatt, B.F, & Cheresh D.A. RBBP9: A tumor-associated serine hydrolase activity
required for pancreatic neoplasia. Proc Natl Acad Sci USA. 2010 Feb 2; 107(5):2189-94. PMCID2836678
14. Murphy, E.A, Shields, D.J, Stoletov, K, Dneprovskaia, E, McElroy, M, Lindquist,J, Acevedo, L, Anand, S,
Majeti, B.K, Tsigelny, I, Saldanha, A, Walsh, B, Hoffman, R.M, Bouvet, M, Klemke, R, Vogt, P.K, Arnold, L,
Wrasidlo, W. & Cheresh D.A. Disruption of angiogenesis and tumor growth with an orally active drug that
stabilizes the inactive state of PDGFRβ/B-RAF. Proc Natl Acad Sci USA. 2010 Mar 2:107(9):4299-304.
PMCID2840076
15. Anand, S, Majeti, B.K, Acevedo, L.M, Murphy, E.A, Mukthavaram, R, Scheppke, L, Huang, M, Shields,
D.J, Lindquist, J.N, Lapinski, P.E, King, P.D, Weis, S.M. and Cheresh, D. A. MicroRNA-132 mediated
loss of p120RasGAP activates endothelium to facilitate pathological angiogenesis. Nature Medicine.
2010, 16:909-14. PMCID-in process.
D. Research Support:
Ongoing Research Support:
R01 CA045726
Cheresh (PI)
04/01/07 - 05/31/12
Regulation of metastasis by alpha V integrin and Src
The major goals of this application will determine how EGFR and Src influence in metastatic pancreatic cancer.
Role: PI
R01 CA095262
Cheresh (PI)
08/01/07 - 05/31/12
Regulation of cell invasion by apoptotic mechanisms
The overall goal of this grant is to characterize mechanisms of cell survival/death among invasive cells.
Role: PI
P30 CA 023100
Carson (PI)
07/01/96 - 04/30/12
Cancer Center Support Grant (CCSG)
This grant provides infrastructure and developmental funds support of the Moores UCSD Cancer Center, an
NCI designated comprehensive cancer center. The Center has 7 research programs, 11 shared resources
and developmental programs organized to foster and promote collaboration and translation of discovery into
advanced patient care toward the ultimate control of cancer.
Role: Co-Investigator
R37 CA050286
Cheresh (PI)
05/01/09 - 03/31/14
VEGF and PDGF in Angiogenesis and Tumor Progression
The goals of this grant are to understand how PDGF and VEGF regulate blood vessel maturation and thereby
contribute to growth and invasion of tumors.
Role: PI
P01 HL057900
Shattil (PI)
02/01/08 - 03/31/13
Integrin Signaling in Hemostasis and Blood Diseases
This project will elucidate the pathways that regulate and coordinate migration of vascular cells.
Role: Co-Investigator
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Program Director/Principle Investigator (Last, First, Middle):
Cheresh, David A.
P01 CA104898
Talamini (PI)
05/01/05 - 08/30/11
Targeting Vessels in Tumors
This project is designed to complement the other projects in this program by providing a gene delivery platform
to test new targets and strategies to disrupt the tumor vasculature and thereby influence the growth and
metastasis of human cancer.
Role: Co-Investigator
R01 CA045726
Cheresh (PI)
07/01/09 - 06/30/11
Regulation of metastasis by alpha V integrin and Src
The goal of this proposal is to combine respective areas of expertise in advanced functional proteomics and
invivo tumor biology models to identify and validate novel therapeutic targets of pancreatic tumor metastasis.
Role: PI
Completed Research Support:
R21 CA129660
Cheresh (PI)
09/01/07 - 08/31/09
Identification of novel pancreatic cancer biomarkers
The goals are to enable detection of pancreatic cancer at the earliest stages and identify novel predictive
markers of disease using a cross-species advanced proteomics approach.
Role: PI
R01 HL78912
Cheresh (PI)
08/01/05 - 07/31/10
Endothelial Barrier Function Regulation by VEGF
The objective of this grant is to understand, at the molecular and biological levels, how endothelial cell (EC)
barrier function is modulated in blood vessels exposed to vascular endothelial cell growth factor (VEGF), and
to determine the consequences of this process in disease.
Role: PI
U54 CA119335
Esener (PI)
09/01/05 - 08/31/10
Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer
The objective of this proposal is to establish a role for nanotechnology as a viable therapeutic option for cancer
patients. We will work with chemists and biologists to develop novel nano-platforms for tumor-targeted delivery
of drugs.
Role: Co-Investigator
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