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Faculty Profile

David Cowburn, Ph.D.

Dr. David Cowburn
 

Professional Interests


David Cowburn's research centers on the application of structural biology, and particularly, nuclear magnetic resonance (NMR), to biological problems. He attempts to develop and apply useful new methods to challenging problems not readily addressed by standard methods.  His work is frequently collaborative.  Some significant structural contributions include the first SH2 domain, the first proapoptopic BCL family member, high affinity complexes of specific SH3/ligands and stapled peptides/targets, and pleckstrin homology domain/PIP interactions.  Methodological contributions cover new isotopic labeling methods, especially segmental labeling by expressed protein ligation, and production of kinases for NMR analysis; analysis of relaxation properties for weak self association, motion of dual domains, contribution of CSA; in-cell NMR with advanced expression methods; mimics of protein-protein interactions,  and molecular dynamics and NMR simulation methods. A significant area of focus is the structural biology of protein domains in intracellular signal transduction, including SH2, SH3, kinase, phosphatase, PH domains, and many others and how natural ligands interact with them. Signaling disorders related to these domains lead to many disease states. Using NMR, there is a strong effort to understand how intrinsically disordered systems can have significant functions roles in the nuclear pore.  

 He was a faculty member at Rockefeller University 1973-2000, and served as the start-up President and CEO of the New York Structural Biology Center, 2000-2010.

 

Selected Publications

Full current list at http://cowburnlab.org/DavidCowburnFullBio.pdf

Google Scholar Listing

Pubmed listing

 

In press or recent publications:

144.      Eryilmaz, E., Shah, N., Muir, T., Cowburn, D., (2014) “Structural and Dynamical Features of Inteins and Implications on Protein Splicing” J. Biol. Chem.  289: 14506-11.

143.    Shah, N. H., Eryilmaz, E., Cowburn, D., Muir, T. W. (2013). Naturally split inteins assemble through a “capture and collapse” mechanism.  J. Am. Chem. Soc., 135, 18673-81.

142.      Eryilmaz, E., Janda, A., Kim, J., Cordero, R.J.B., Cowburn, D., and Casadevall, A. (2013). Global structures of IgG isotypes expressing identical variable regions. Molecular Immunology 56 588-98

 141.       Shah, N. H., Eryilmaz, E., Cowburn, D., Muir, T. W. (2013); Extein Residues Play an Intimate Role in the Rate-Limiting Step of Protein Trans-Splicing Journal of the American Chemical Society 135 5839-47 

140.    Chen, H., Huang, Z., Dutta, K., Blais, S., Neubert, T.A., Li, X., Cowburn, D., Traaseth, N.J., and Mohammadi, M. (2013). Cracking the Molecular Origin of Intrinsic Tyrosine Kinase Activity through Analysis of Pathogenic Gain-of-Function Mutations. Cell reports 4 376-384

139.      Bhattacharya S, Ho J, Orlova A, Khajeh JA, Cowburn D, Bu Z. (2013) Ligand induced dynamics changes in extended PDZ domains from NHERF1  J Mol Biol. 2013 425 2509-28

138.      Cucuringu, M., Singer, A., Cowburn, D. (2012). Eigenvector synchronization, graph rigidity, and the molecule problem. Information and Inference 1 21-61 P

137.      Janda, A., Eryilmaz, E., Nakouzi, A., Cowburn, D., and Casadevall, A. (2012). Variable region identical immunoglobulins differing in isotype express different paratopes. J Biol Chem.  287 35409-17 

136.   Xu, R., Liu, D., and Cowburn, D. (2012). Abl kinase constructs expressed in bacteria: facilitation of structural and functional studies including segmental labeling by expressed protein ligation. Mol Biosyst 8 1878-1885  

135.      Piserchio A, Cowburn D, Ghose R. Expression and Purification of Src-family Kinases for Solution NMR Studies. (2012) Methods Mol Biol. 831 111-31.   PMCID: 22167671

134.      Bhattacharya S, Zhang H, Cowburn D, Debnath AK. Novel structures of self-associating stapled peptides. Biopolymers. 2012 97 253-64 PMCID: 3306222 P

133.      Kalinina J, Dutta K, Ilghari D, Beenken A, Goetz R, Eliseenkova AV, Cowburn D, Mohammadi M. (2012) “The alternatively spliced acid box region plays a key role in FGF receptor autoinhibition”, Structure 20  77-88  

Reviewed publications not in PubMed :

107.      Goger, M. J., McDonnell, J. M., and Cowburn, D. (2003). “Using cryoprobes to decrease acquisition times of triple-resonance experiments used for protein resonance assignments”. Spectroscopy-an International Journal 17, 161-167.

60.       Digennaro, F.; Cowburn, D.  "Simulated annealing as an approach to time-frequency conversion in NMR" (1992) J. Mag. Res.  96 582-8    

56.       Henderson, G. B.; Glushka, J.; Cowburn, D.; Cerami, A.   "Synthesis and   NMR characterization   of   the  trypanosomatid  metabolite N1,N8 –bis (glutathionyl) spermidine disulfide  (trypanothione  disulphide)" (1990) J. Chem. Soc. Perkin Trans. I 911-914            

52.       Morris, G.A.; Cowburn, D.  (1989)  "Suppression of Artefacts in  Nuclear Overhauser Effect Difference Spectroscopy by Reference Deconvolution" Magnetic Resonance in Chemistry 27 1085-1089             

50.       Glushka, J.; Lee, M.; Coffin, S.; Cowburn, D.  "15N Chemical Shifts of Backbone Amides in Bovine Pancreatic Trypsin Inhibitor and Apamin" (1989) J. Am. Chem. Soc.  111 7716-7722 and (1990) 112 2843

49.       Ashcroft, J.; LaPlante, S.; Borer, P.N.; Cowburn, D.   "Sequence Specific 13C NMR Assignment   of non-protonated carbons in [d (TAGCGCTA) ­­2] using Proton Detection" (1989)  J.  Am.  Chem.  Soc111 362-365

48.       Jain, D. C.; Sapse, A. M.; Cowburn, D.  "Solvent effects on some imine-carboxyl complexes" (1988) J. Phys. Chem92 6847-6849                                                

45.       Glushka, J.; Cowburn, D.  15N Chemical Shifts of the Backbone Amides in Bovine Pancreatic Tryspin Inhibitor" (1987) J. Am. Chem. Soc.  109 7879-7881. 

43.       Schussheim, A. ; Cowburn, D. "Digital  Signal  Processing  of  Two-Dimensional  NMR  spectra  using  Linear  Predictive Singular Value Decomposition" (1987) J. Magn. Res.  71 379-383                                        

42.       Ortiz-Polo, G.; Krishnamoorthi, R.; Markley, J. L.; Live, D.  H.; Davis, D. G.; Cowburn, D.  "Natural Abundance 15N NMR Spectroscopy Studies of Turkey Ovomucoid Third Domain: Assignment of Peptide 15N  Resonances to the Residues at the Reactive Site Region via Proton-Detected Multiple Quantum Coherence" (1986) J.  Magn.  Res. 68 303-310     

41.       Sapse, A.M.; Fugler, L. M. ; Cowburn, D.  "An Ab Initio Study of Intermolecular Hydrogen Bonding Between Small Peptide Fragments" (1986) Int. J. Quantum Chemistry 29 1241-1251            

37.       Live, D. H.; Kojiro, C. L.; Cowburn, D.; Markley, J. L.  "Identification of proton NMR signals from the metal-ligands of Cadmium substituted plastocyanin via two-dimensional multi-quantum  detection  in  the  absence of explicitly resolved 1H-113Cd coupling"  (1985) J. Am. Chem. Soc.  107 3043-3044                                                                                             

35.       Live, D. H.; Delgano, D.; Armitage, I. A.; Cowburn, D.   "Cd   NMR spectra of Metallothionein observed via proton detected multiquantum spectroscopy" (1985) J. Am. Chem. Soc.  107 441-443                                                                                                                

34.       Davis, D. G.; Cowburn, D.  "Suppression of solvent lines in 13C NMR" (1984) J. Magn. Res.  62 128-130    

33.       Live, D. H.; Davis, D. G.; Agosta, W. C.; Cowburn, D.  "Observation of thousand-fold enhancement for   15N NMR via multiple quantum coherences: Studies of large peptides." (1984) J.  Am.  Chem.  Soc. 106 6104-6105                                                                          

32.       Coffin, S.; Limm, M.; Cowburn D.   "Correlation  of  13C  and 1H chemical  shifts  in  bovine  high  density  lipoprotein  from two-dimensional NMR" (1984) J. Magn. Res. 59 268-274                                  

31.       Live, D. H.; Davis, D. G.; Agosta, W.  C.; Cowburn, D.  "Long range hydrogen bond mediated effects in peptides: 15N NMR study of gramicidin S in water and organic solvents” (1984) J.  Am.  Chem. Soc. 106 1939-1942.       

29.       Davis, D. G.; Agosta, W. C.; Cowburn, D.  "Long-range proton-nitrogen spin coupling constants via polarization-enhanced two-dimensional 15N NMR" (1983) J. Am. Chem. Soc. 105 6189-6190           

28.       Cowburn, D.; Live, D. H.; Fischman, A. J.; Agosta, W. C.  "Side chain conformations of oxytocin and vasopressin studied by NMR observation of isotopic isomers" (1983) J. Am. Chem. Soc.  105 7435-7442                                                    

27.       Fotadar, U.; Cowburn, D.  "Syntheses of 1-13C and 3-13C isotopic isomers of Aspartic and Glutamic acids" (1983) J. Label. Cmpds. Radiopharm. 20 1003-1009     

26.       Davis, D. G.; Live, D. H.; Agosta, W. C.; Cowburn, D. "Spin Connectivites to protons of  13C  and 15N NMR spectra by selective suppression" (1983) J. Magn. Res. 53 350-354                             

25.       Live, D. H.; Davis, D. G.; Agosta, W. C.; Cowburn, D. "Conformations of side chains of somatostatin: Very high field proton NMR studies" (1982) Org. Magn. Reson. 19 211-215                         

20.       Fischman, A. J.; Live, D. H.; Wyssbrod, H. R.; Agosta, W.  C.; Cowburn, D.  "Torsion angles in the cystine bridge of oxytocin in aqueous solution; measurements of circumjacent vicinal couplings between 1H, 13C and 15N." (1980) J. Am. Chem. Soc. 102 2533-9                                         

16.       Live, D. H.; Wyssbrod, H. R.; Fischman, A. J.; Agosta, W.  C.; Bradley, C.; Cowburn, D.  "A study of the peptide hormone oxytocin and of prolylleucylglycinamide by 15N NMR."  (1979)  J.  Am.  Chem. Soc. 101 474-9            

14.       Fischman, A. J.; Wyssbrod, H. R.; Agosta, W.  C.; Cowburn, D. "Heteronuclear vicinal coupling constants and site-specific isotopic substitution in the investigation of rotational isomerism in leucine." (1978) J. Am. Chem. Soc. 100 54-8                          

11.       Wouters, J. M.; Petersson, G. A.; Agosta, W. C.;  Field, F. H.; Gibbons,  W.  A. ;  Wyssbrod, H. R.; Cowburn, D. "Reference line-shape adjusted difference NMR spectroscopy II.  Experimental Verification." (1977) J. Magn. Reson. 28 93-104.                

7.         Stoner, E. C.; Cowburn, D.; Craig, L. C. "Examination of volatile metabolites in plasma." (1975) Anal. Chem. 47 344-6   

 

 

 

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Contact

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Ullmann Building, Room 423
Bronx, NY 10461

Tel: 718.430.8621
david.cowburn@einstein.yu.edu

 
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Media Coverage

Chemical & Engineering News interviews David Cowburn, Ph.D., about conflicting reports on the efficacy of stapled peptides, protein fragments chemically locked into an α-helical shape, and their potential for drug development. Dr. Cowburn, who has used stapled peptides to interfere with HIV assembly, notes that stapling is not easy and many adjustments need to be made to create a peptide that will work successfully within a cell. Dr. Cowburn is professor of biochemistry and of physiology & biophysics.

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