Scott Walsh, Ph.D.
Dr. Walsh’s primary research interest involves understanding how proteins interact with each other at the structural level. He has made a significant impact in the fields of protein design and protein-protein interactions. His research interests include the specific interactions between cellular proteins, called cytokines, and specific proteins on cell surfaces, called cytokine receptors. These cytokine-cytokine receptor interactions trigger intercellular communication that determines how an immune cell functions. One such cytokine-cytokine receptor interaction that is of particular interest to Dr. Walsh is interleukin-7 (IL-7). IL-7 signaling is essential for the development, proliferation, and stability of T cells in the immune system. The IL-7 pathway is of significant medical importance as under-stimulation leads to severe combined immunodeficiency and over-stimulation of IL-7 has been implicated in the progression of several autoimmune diseases including inflammatory bowel disease, host-versus-graft disease, multiple sclerosis, and finally several leukemias. In the Schneider group, we are using designed hydrogels for delivery of key cell signaling proteins like IL-7 for sustained delivery in rebuilding T cells during immunodeficient states.
1) structural biology and biophysics, 2) x-ray crystallography and NMR spectroscopy,
3) protein design and engineering, 4) phage display mutagenesis, 5) cytokine-cytokine receptor interactions
Dr. Walsh’s research goal is to understand at the structural and functional levels how cells talk to each using signaling molecules called cytokines and cytokine receptors of the immune system. Using this knowledge, he is developing novel molecules to either enhance or inhibit these signaling pathways. He has focused on deciphering the language used by T cells involving their use of IL-7 signaling proteins. He has active intramural NIH collaborations with Drs. Scott Durum, Hyun Park, Terry Fry, Jim McMahon, and Joel Schneider and with the extramural scientific community.
Dr. Walsh is an expert in using numerous structural and biophysical methods including x-ray crystallography, NMR spectroscopy, surface plasmon resonance, circular dichroism, fluorescence, analytical ultracentrifugation, calorimetry, and light scattering. He is also an expert molecular biologist and interested in using phage display mutagenesis to probe and evolve protein function and evolution.
Selected Key Publications
Activated T cells secrete an alternatively spliced form of common γ-chain that inhibits cytokine signaling and exacerbates inflammation.Immunity. 19: 910-23, 2014. [ Journal Article ]
- Proc Natl Acad Sci U S A. 110: E1762-70, 2013. [ Journal Article ]
Structural insights into the common γ-chain family of cytokines and receptors from the interleukin-7 pathway.Immunol Rev. 250: 303-16, 2012. [ Journal Article ]
- Proc Natl Acad Sci U S A. 109: 2503-8, 2012. [ Journal Article ]
- Structure. 17: 54-65, 2009. [ Journal Article ]
Dr. Scott Walsh completed his B.S. in biochemistry from the University of Illinois Champaign-Urbana and earned a Ph.D. in structural biology and biophysics from the University of Pennsylvania. He was a Burroughs Wellcome Fund Postdoctoral Fellow of the Life Sciences Research Foundation in the Department of Biochemistry & Molecular Biology at the University of Chicago. For 13 years, Dr. Walsh was a professor at the Ohio State University, the University of Maryland Biotechnology Institute, and the University of Maryland College Park. In 2017, he joined the Chemical Biology Laboratory, Center for Cancer Research, NCI as a Staff Scientist.