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Molecular Medicine


Luke Wiseman, Ph.D.

Associate Professor
Department of Molecular Medicine
California Campus
Laboratory Website
(858) 784-8820

Scripps Research Joint Appointments

Department of Chemical Physiology
Faculty, Graduate Program

Research Focus

Protein misfolding and human disease

Conversion of genetic information into functional protein products requires the proper folding of polypeptide chains in the crowded intracellular environment. Disruption of these folding pathways through exposure to either environmental or genetic factors is associated with numerous human diseases – collectively referred to as protein misfolding diseases. Using proteomic, biophysical and cell biological approaches, work in the Wiseman lab is directed towards understanding the physical, chemical and biological factors that dictate intracellular protein folding as it relates to human disease. Currently, we have three ongoing projects focused on protein folding in vivo: 1) development of novel biosensors that report on protein folding in the complex intracellular environment; 2) characterization of mitochondrial folding efficiency in the context of neurodegenerative disease; and 3) elucidation of the impact of intracellular signaling pathways on protein folding and trafficking in the early secretory pathway.


B.S., Chemistry, University of Virginia, 2001
Ph.D., Chemistry, The Scripps Research Institute, 2005

Selected References

Rainbolt, TK; Lebeau, J; Puchades, C; Wiseman, RL (2016) Reciprocal Degradation of YME1L and OMA1 Adapts Mitochondrial Proteolytic Activity During Stress, Cell Reports, 14, 2041-2049 

Plate, L; Cooley, CB; Chen, JJ; Paxman, RJ; Gallagher, CM; Madoux, F; Genereux, JC; Dobbs, W; Garza, D; Spicer, TP; Scampavia, L; Brown, SJ; Rosen, H; Powers, ET; Walter, P; Hodder, P; Wiseman, RL*; Kelly JW* (2016) Small Molecule Proteostasis Regulators that Reprogram the ER to Reduce Extracellular Protein Aggregation, eLIFE, in press

Rainbolt, TK; Saunders, JM; Wiseman RL (2015) YME1L Degradation Reduces Mitochondrial Proteolytic Capacity During Oxidative Stress, EMBO Reports, 16, 97-106. 

Genereux, JC; Qu, S; Zhou, M; Ryno, LM; Wang, S; Shoulders MD; Kaufman, RJ; Lasmezas, CI; Kelly, JW; Wiseman RL (2015) Unfolded Protein Response-Induced ERdj3 Secretion Links ER Stress to Extracellular Proteostasis, EMBO J, 34, 4-19 

Chen, JJ; Genereux, JC; Qu, S; Hulleman, JD; Shoulders, MD; Wiseman, RL (2014) Increasing ER Quality Control Stringency Through ATF6 Activation Reduces the Secretion and Extracellular Aggregation of Destabilized Variants of an Amyloidogenic Proteins, Chemistry & Biology, 21, 1564-1574 

Cooley, CB; Ryno, LM; Plate, L; Morgan, GJ; Hulleman, JD; Kelly, JW; Wiseman, RL (2014) Unfolded Protein Response Activation Reduces Secretion and Extracellular Aggregation of Amyloidogenic Immunoglobulin Light Chain, Proc. Natl. Acad. Sci. USA, 111, 13046-13051. 

Ryno, LM; Genereux, JC; Naito, T; Morimoto, RI; Powers, ET; Shoulders, MD; Wiseman RL (2014) Characterizing the Altered Cellular Proteome Induced by the Stress Independent Activation of Heat Shock Factor 1, ACS Chemical Biology, 9, 1273-1283.

Rainbolt, TK; Atanassova, N; Genereux, JC; Wiseman, RL (2013) Stress-Regulated Translational Attenuation Adapts Mitochondrial Protein Import Through Tim17A Degradation, Cell Metabolism, 18, 908-919.

Shoulders, MD; Ryno, LM; Cooley, CB; Kelly, JW; Wiseman, RL (2013) Broadly Applicable Methodology for the Rapid and Dosable Small Molecule-Mediated Regulation of Transcription Factors in Human Cells, J. Am. Chem. Soc., 135, 8129-8135. 

Shoulders, MD; Ryno, LM; Genereux, JC; Moresco, JJ; Tu, PG; Yates, III, JR; Su, AI; Kelly, JW; Wiseman, RL (2013) Stress-independent Activation of XBP1s and/or ATF6 Reveals Three Functionally Diverse ER Proteostasis Environments, Cell Reports, 3, 1279-1292.

Molecular Medicine Seminar Series
Center for Physiological Proteomics
Department Contacts

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
Johnson, Eric
Kanaji, Taisuke
Koziol, James
Lamia, Katja
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Nicholson, Laura
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.
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John

FL Faculty

Bannister, Thomas
Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Joazeiro, Claudio
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
Ye, Li

Adjunct Faculty