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. Using NMR, there is a strong effort to understand how intrinsically disordered systems can have significant functions roles in the nuclear pore. This project involves also scattering techniques and extensive simulation to probe kinetic properties. 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.
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.
In press or recent publications:
148. Hough, L., ... Cowburn, D. "The molecular mechanism of nuclear transport revealed by atomic scale measurements", eLife 2015;10.7554/eLife.10027
147. Ferrage, F., Dutta, K., Cowburn, D. “Identification of Hydrophobic Interfaces in Protein-Protein Complexes by Selective Saturation Transfer NMR Spectroscopy”Molecules, 20, in press.
146. Wilner, Samantha; Sparks, Samuel; Cowburn, David; Girvin, Mark; Levy, Matthew (2015) , "Controlling lipid micelle stability using oligonucleotide headgroups" J. Am. Chem. Soc., 137 2171-4P
145. Karp, J.; Eryilmaz, E.; Cowburn, D. (2014) "Correlation of chemical shifts predicted by molecular dynamics simulations for partially disordered proteins” J. Biomol NMR, 61 35-45
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
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. Soc. 111 362-365
48. Jain, D. C.; Sapse, A. M.; Cowburn, D. "Solvent effects on some imine-carboxyl complexes" (1988) J. Phys. Chem. 92 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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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.