Scott Walsh

Ph.D. - University of Pennsylvania

Post Doctoral - University of Chicago

Our research focuses on understanding the roles of structure, dynamics and energetics in molecular recognition among different classes of cytokines and their receptors. The current system of interest includes interleukins 7 and 9 (IL-7 and IL-9), members of a family of cytokines that use a common receptor, gc, for activation. The contributions of structure and dynamics to the interactions between IL-7, IL-9, and gc are being assessed using both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. The extent to which thermodynamic and kinetic properties govern molecular recognition will be determined by various biophysical and biochemical methods. A comprehensive understanding of the binding determinants for this class of hormone-receptor interactions will also contribute to our development of novel peptide/protein therapeutic agents using both rational protein design and phage display techniques. Inhibition or enhancement of cytokine-receptor interactions by such agents will have biomedical implications for the various deficiencies, allergies, and cancers caused by under- or over- stimulation of this family of cytokines.

Recent Publications:

Wickham J Jr and Walsh ST (2007) "Crystallization and preliminary X-ray diffraction of human interleukin-7 bound to unglycosylated and glycosylated forms of its alpha-receptor" Acta Crystallogr Sect F Struct Biol Cryst Commun. 63(Pt 10):865-9.

Walsh STR and Kossiakoff A (2006) "Crystal Structure and Site 1 Binding Energetics of Human Placental Lactogen" J Mol Biol 358:773-84.

Walsh STR, Sylvester JE and Kossiakoff A (2004) "The high- and low-affinity receptor binding sites of growth hormone are allosterically coupled" PNAS 101:17078-83.

Walsh STR, Cheng RP, Wright WW, Alonso DOV, Daggett V, Vanderkooi JM and DeGrado WF (2003) "The hydration of amides in helices; a comprehensive picture from molecular dynamics, IR, and NMR" Protein Sci 12:520-31.

Walsh STR, Jevitts LM, Sylvester JE and Kossiakoff AA (2003) "Site2 binding energetics of the regulatory step of growth hormone-induced homodimerization" Protein Sci 12:1960-70.