Scripps Research Logo

Molecular Medicine

Faculty

Jeffery Kelly, Ph.D.

Lita Annenberg Hazen Professor of Chemistry
Co-chair
Department of Molecular Medicine
California Campus
Laboratory Website
jkelly@scripps.edu
(858) 784-9605

Scripps Research Joint Appointments

Department of Chemistry
The Skaggs Institute for Chemical Biology
Faculty, Graduate Program

Research Focus

Chemical Biology and Biophysical Chemistry

A central focus of our research is to understand the principles of protein folding and to comprehend the basis for misfolding and/or aggregation diseases such that we can develop novel therapeutic strategies using chemistry, biophysical and biological approaches.

A multidisciplinary approach to understanding degenerative diseases linked to protein aggregation is a main focus of our laboratory. We concentrate on Alzheimer's disease, as well as the transthyretin- and light-chain-based amyloid diseases. Mechanistic studies of protein aggregation have led to small molecule and macromolecular amyloid fibril inhibition strategies, including the drug, tafamidis, discovered by the Kelly lab and sold by Pfizer. Our efforts to seek an aggregate structure-proteotoxicity relationship have led to insight into the etiology of these pathologies. Chemical synthesis of small molecule inhibitors designed to manipulate protein energetics is a significant component of our research program. We also use cell-based screens to discover mediators of the protein homeostasis network, including stress-responsive signaling pathway activators (in collaboration with the Wiseman lab) and autophagy activators, which should be generally useful to ameliorate amyloid diseases.

Investigation into lysosomal storage diseases are underway wherein small molecules that enhance the proteostasis network capacity of the secretory pathway and pharmacologic chaperones are being sought to correct genetic defects in the folding and trafficking of enzymes that are critical for lysosome function and therefore life.

All of the projects discussed thus far utilize bioorganic and biophysical chemistry approaches in combination with biological studies carried out in collaboration with several laboratories. 

The Kelly lab in collaboration with the Wong lab discovered the enhanced aromatic sequon—sequences that are more efficiently N-glycosylated by cellls and which stabilize the native state of proteins that they are incoporated into as a consequence of aromatic side chain–N-glycan interactions. Using chemically synthesized WW domain analogs wherein we vary the aromatic side chain and the sugar, we are learning a great deal about the underpinnings of this stabilizing interaction.

Developing synthetic methodology to accomplish medicinal chemistry towards the development of drugs for several activators of proteostasis capacity is a central component of the lab. In addition, we use these methods to scrutinize the hypothesis that we can discover drugs via our Inverse Drug Discovery approach.

Education

B.S., Chemistry, State University of New York at Fredonia, 1982
Ph.D., Chemistry, The University of North Carolina at Chapel Hill

Professional Experience

2017- present  Co-Chairman, Department of Molecular Medicine, The Scripps Research Institute
2008-2017       Chairman, Molecular and Experimental Medicine, The Scripps Research Institute
2000-2008       Dean of Graduate and Postgraduate Studies, Scripps Graduate Program, The Scripps Research Institute
2000-2006       Vice President, Academic Affairs, The Scripps Research Institute
1997-1997       Professor of Chemistry, Texas A&M University
1996-1996       Visiting Investigator, Memorial Sloan-Kettering Institute
1995-1997       Associate Professor of Chemistry, Texas A&M University
1989-1995       Assistant Professor of Chemistry, Texas A&M University
1986-1989       NIH Postdoctoral Fellow with Dr. E. Thomas Kaiser, The Rockefeller University

Awards & Professional Activities

Searle Scholar Award in Biomedical Sciences, 1991-1994 Camille and Henry Dreyfus Teacher Scholar Award, 1994 Texas A&M University Teacher Scholar Award, 1994-1995 The Biophysical Society National Lecturer, 1999 The Protein Society - Dupont Young Investigator Award, 1999 Alumni Distinguished Achievement Award, State University of New York at Fredonia, 2000 Arthur C. Cope Scholar Award, American Chemical Society, 2001 National Institutes of Health Merit Award, 2006 The American Peptide Society Vincent du Vigneaud Award, 2008 The American Peptide Society Rao Makineni Lectureship (Award), 2011 The Protein Society Emil Thomas Kaiser Award, 2011 American Chemical Society Ralph F. Hirschmann Award in Peptide Chemistry, 2012 Biopolymers Murray Goodman Memorial Prize, 2012  Royal Society of Chemistry Jeremy Knowles Award, 2016 American Academy of Arts and Sciences, Elected member, 2016 Jacob and Louise Gabbay Award in Biotechnology and Medicine, 2016 American Institute of Chemists Chemical Pioneer Award, 2017

Selected References

Deechongkit, S.; Nguyen, H.; Dawson, P.E.; Gruebele, M.; Kelly, J.W. "Context Dependent Contributions of Backbone H-Bonding to b-Sheet Folding Energetics" Nature 2004, 430, 101-105.

Hammarstrom, P.; Wiseman, R.L.; Powers, E.T.; Kelly, J.W., "Prevention of Transthyretin Amyloid Disease by Changing Protein Misfolding Energetics" Science 2003, 299, 713-716.

Sekijima, Y.; Wiseman, R.L.; Matteson, J.; Hammarström, P.; Miller, S.R.; Balch, W.E.; Kelly, J.W. "Biological and Chemical Basis for Tissue Selective Amyloid Disease" Cell 2005, 121, 73-85.

Balch, W.E.; Morimoto, R.I.; Dillin, A.; Kelly, J.W. "Adapting Proteostasis For Disease Intervention" Science 2008, 319, 916-919.

Links

The Skaggs Institute for Chemical Biology

Molecular Medicine Seminar Series

CA Faculty

Asahara, Hiroshi
Balch, William E.
Boddy, Michael
Buxbaum, Joel
Catz, Sergio
Conti, Bruno
Cravatt, Benjamin
D'Lima, Darryl
DerMardirossian, Celine
Deryugina, Elena
Elias, Darlene
Encalada, Sandra
Felding, Brunhilde
Fowler, Velia
Friedlander, Martin
Gerace, Larry
Gottesfeld, Joel
Griffin, John
Hanneken, Anne
Heeb, Mary Jo
Henderson, Scott
Hoch, James
Joazeiro, Claudio
Johnson, Eric
Kanaji, Taisuke
Kay, Steve
Kelly, Jeffery
Koziol, James
Lamia, Katja
Lazzerini Denchi, Eros
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Paulson, James C.
Perego, Marta
Petrascheck, Michael
Pollard, Kenneth Michael
Quigley, James P.
Reed, Steven
Roberts, Edward
Rosen, Hugh
Ruggeri, Zaverio
Russell, Paul
Saez, Enrique
Smider, Vaughn
Srinivasan, Supriya
Steinhubl, Steven
Sutcliffe, J.
Tan, Eng
Topol, Eric
Vanderklish, Peter
Vogt, Peter K.
Waalen, Jill
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John


FL Faculty

Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Kamenecka, Theodore
Kissil, Joseph
Luo, Junli
McDonald, Patricia
Miller, Courtney
Niedernhofer, Laura
Phinney, Donald G.
Robbins, Paul
Scampavia, Louis
Schimmel, Paul
Smith, Roy
Spicer, Timothy


Affiliated Faculty

Cline, Hollis
Kojetin, Douglas
Lairson, Luke
Paegel, Brian
Rumbaugh, Gavin
Shen, Ben
Solt, Laura A
Su, Andrew
Wu, Chunlei


Adjunct Faculty