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Luke Wiseman, Ph.D.

Associate Professor
Department of Molecular Medicine
California Campus
Laboratory Website
Scripps VIVO Scientific Profile
wiseman@scripps.edu
(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.

Education

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

Professional Experience

2016-2017 Associate Professor (Joint Appointment), Chemical Physiology, The Scripps Research Institute
2016-2017 Associate Professor, Molecular and Experimental Medicine (MEM), The Scripps Research Institute
2013-2016 Assistant Professor (Joint Appointment), Chemical Physiology, The Scripps Research Institute
2009-2016 Assistant Professor, Molecular and Experimental Medicine (MEM), The Scripps Research Institute
2006-2009 NIH Postdoctoral Fellow, School of Medicine, New York University

Selected References

All Publications

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.