Program Director/Principal Investigator (Last, First, Middle):
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Cowburn, David
Professor
eRA COMMONS USER NAME (credential, e.g., agency login)
cowburn
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)
Manchester U. UK
King’s College, London U. UK
Columbia University, Postdoc Assoc.
Columbia University, Postdoc Fellow
B.Sc.Hon
Ph.D.
06/65
06/70
6/70-3/73
7/71-3/73
Biochemistry
Molecular Biophysics
Neurochemistry
Neurosciences
A. Personal Statement
The goal of this research is to provide dynamic and structural insights into activation and control mechanisms
of the receptor tyrosine kinase FGFR2K. I have substantial experience and qualifications in using NMR for
structure and dynamics determination and understanding their relation to function. We have extensive
experience in such studies of non-receptor tyrosine kinases, of SH2 domains, and related systems. The
proposed FGFR system studies with Professor Mohammadi represent a unique opportunity to join my
specialist knowledge to his comprehensive structural, biochemical, and pharmacological knowledge of the
FGFR systems, and promises to provide both of us with potential avenues for future translational research
building on the fundamental issues to be addressed in this proposal.
B. Positions and Honors
1973-2000
Assistant /Associate Professor, Rockefeller U.; Head of Lab. of Physical Biochemistry
2000-2010
Head, Laboratory of Physical Biochemistry; President & CEO, New York Structural Biology
Center
2003Adjunct Faculty, Rockefeller University; Adjunct Scientist, Columbia University; Adjunct Faculty,
Mount Sinai School of Medicine
Other experience and professional memberships
Frequent ad-hoc reviewer of intra- and extra-mural programs, NIH, NSF, DoD, DoE, EC
2003-2008
Advisory Committees, NMRFAM, Madison, WI; CSCC, Athens, GA
2004 - Advisory Boards, p53 Regulators and Effectors (P01) PI Aaronson, Mount Sinai: Macromolecular
Assemblies Institute, (NSF) PI Stark, CUNY; HWB-NMR Center (Wellcome), PI Overduin, U. Birmingham, UK
2008 - Associate Editorships, The Open Cell Signaling Journal ; PLOS Computational Biology
2008 - SAB member, Coferon LLC
Honors
1962-65
1971-1973
1981
2001
State Scholar
Research Fellow, NIMH Training Program, Columbia P&S
D.Sc. by examination, London University
Fellow, New York Academy of Sciences
PHS 398/2590 (Rev. 06/09)
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Program Director/Principal Investigator (Last, First, Middle):
C. Selected Peer-reviewed Publications
Most relevant to the current application
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5.
Ferrage, F., K. Dutta, A. Shekhtman, and D. Cowburn, Structural determination of biomolecular
interfaces by nuclear magnetic resonance of proteins with reduced proton density. J Biomol NMR,
2010. 47: p. 65-77.
Bhattacharya, S., Z. Dai, J. Li, S. Baxter, D.J. Callaway, D. Cowburn, and Z. Bu, A Conformational
Switch in the Scaffolding Protein NHERF1 Controls Autoinhibition and Complex Formation. J Biol
Chem, 2010. 285(13): p. 9981-94.
Piserchio, A., R. Ghose, and D. Cowburn, Optimized bacterial expression and purification of the c-Src
catalytic domain for solution NMR studies. J Biomol NMR, 2009. 44(2): p. 87-93.
Liu, D., R. Xu, and D. Cowburn, Segmental isotopic labeling of proteins for nuclear magnetic
resonance. Meth Enzymol, 2009. 462: p. 151-75.
Burz, D., K. Dutta, D. Cowburn, and A. Shekhtman, In-cell NMR for protein-protein interactions (STINTNMR). Nat Protoc, 2006. 1(1): p. 146-52.
Additional recent publications of importance to the field (in chronological order)
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Camarero, J.A., D. Fushman, D. Cowburn, and T.W. Muir, Peptide chemical ligation inside living cells:
in vivo generation of a circular protein domain. Bioorg Med Chem, 2001. 9(9): p. 2479-84.
McDonnell, J.M., R. Calvert, R.L. Beavil, A.J. Beavil, A.J. Henry, B.J. Sutton, H.J. Gould, and D.
Cowburn, The structure of the IgE Cepsilon2 domain and its role in stabilizing the complex with its highaffinity receptor FcepsilonRIalpha. Nat Struct Biol, 2001. 8(5): p. 437-41.
Camarero, J.A., A. Shekhtman, E.A. Campbell, M. Chlenov, T.M. Gruber, D.A. Bryant, S.A. Darst, D.
Cowburn, and T.W. Muir, Autoregulation of a bacterial sigma factor explored by using segmental
isotopic labeling and NMR. Proc Natl Acad Sci U S A, 2002. 99(13): p. 8536-41.
Shekhtman, A., R. Ghose, M. Goger, and D. Cowburn, NMR structure determination and investigation
using a reduced proton (REDPRO) labeling strategy for proteins. FEBS Lett, 2002. 524(1-3): p. 177-82.
Romanelli, A., A. Shekhtman, D. Cowburn, and T. Muir, Semisynthesis of a segmental isotopically
labeled protein splicing precursor: NMR evidence for an unusual peptide bond at the N-extein-intein
junction. Proc Natl Acad Sci U S A, 2004. 101(17): p. 6397-402.
Mukherjee, M., K. Dutta, M. White, D. Cowburn, and R. Fox, NMR solution structure and backbone
dynamics of domain III of the E protein of tick-borne Langat flavivirus suggests a potential site for
molecular recognition. Protein Sci, 2006. 15(6): p. 1342-55.
Muralidharan, V., K. Dutta, J. Cho, M. Vila-Perello, D.P. Raleigh, D. Cowburn, and T.W. Muir, Solution
structure and folding characteristics of the C-terminal SH3 domain of c-Crk-II. Biochemistry, 2006.
45(29): p. 8874-84.
Bhattacharya, S., H. Zhang, A.K. Debnath, and D. Cowburn, Solution structure of a hydrocarbon
stapled peptide inhibitor in complex with monomeric C-terminal domain of HIV-1 capsid. J Biol Chem,
2008. 283(24): p. 16274-8.
Pellecchia, M., I. Bertini, D. Cowburn, C. Dalvit, E. Giralt, W. Jahnke, T.L. James, S.W. Homans, H.
Kessler, C. Luchinat, B. Meyer, H. Oschkinat, J. Peng, H. Schwalbe, and G. Siegal, Perspectives on
NMR in drug discovery: a technique comes of age. Nat Rev Drug Discov, 2008. 7(9): p. 738-45.
Zhang, H., Q. Zhao, S. Bhattacharya, A.A. Waheed, X. Tong, A. Hong, S. Heck, F. Curreli, M. Goger,
D. Cowburn, E.O. Freed, and A.K. Debnath, A cell-penetrating helical peptide as a potential HIV-1
inhibitor. J Mol Biol, 2008. 378(3): p. 565-80.
D. Research Support
ACTIVE
R01GM086868 Muir (PI)
PHS 398/2590 (Rev. 06/09)
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Program Director/Principal Investigator (Last, First, Middle):
NIH/NIGMS
Segmental labeling for protein structure by NMR
This project studies how inteins catalyze and regulate the various steps of protein splicing and trans-splicing,
with a goal of development of a general vehicle for controlling protein structure and function in vivo with
numerous general and structural biological applications.
1R01GM084278-01 Ghose (PI)
09/1/2008-08/31/2013
NIH/NIGMS
Catalytic Domain Dynamics in Protein Kinases
This project is involved with elucidating the multiple spatial as well as temporal processes involved in the
catalytic activation of two key cell signaling molecules namely, c-Src and ERK2. The catalytic activity of these
two molecules is tightly regulated in healthy cells. However, this control is lost in a variety of human cancers
and proliferative diseases. Thus, a clear understanding of the functioning of these molecules in space and time
will improve current anticancer therapies while helping the design of novel strategies targeting this deadly
disease.
R01AI081604-01 Debnath (PI)
03/01/2009-02/28/2011
NIH
Rational Design of Antivirals Targeted to HIV-1 Capsid
The goals of the proposed studies are two-fold: 1) To use structure-based rational design to develop potent
cell-penetrating peptides and small molecules that inhibit HIV-1 assembly and maturation and 2) To
establish the mechanism by which these inhibitors identified in these studies will serve as probes for
elucidating the underlying structural requirements in forming immature and mature virus particles, which are
critical for viral assembly and infectivity.
Subcontract at NYSBC
PENDING
U54
Girvin (PI) at AECOM
07/01/10-06/30/15
Membrane Protein Structure by NMR
A subcontract portion of this Protein Structure Initiative proposal will be used to develop new methods for NMR
structure determination using expressed protein ligation and segmental labeling.
RECENTLY COMPLETE
5RO1GM47021-16 Cowburn (PI)
02/01/1992-03/31/2010
.
NIH/ NIGMS
Structural Biology of Protein Kinases
This project will extend the knowledge of the structure, in solution, of the large protein tyrosine kinase, Abelson
(Abl) and its complexes in intracellular signal transduction using both established NMR and molecular biology
approaches, and new technologies. The latter will extend those already developed here, including segmental
labeling using expressed protein ligation, domain structures with consolidated ligands, and direct determination
of segmental motion of multidomain proteins from relaxation studies.
2R01CA089362 Hammerling (PI)
06/01/2005-05/31/2010
NIH/NCI
Novel Receptors of Vitamin A in the Cytoplasm
This project will investigate the structural basis for PKC modulation by chemical and structural changes of the
Zing finger C-terminal domain by physiological agents.
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