R. Luke Wiseman, Ph.D. Associate Professor Department of Molecular

Wiseman CV

R. Luke Wiseman, Ph.D. Associate Professor Department of Molecular Medicine The Scripps Research Institute MEM 220 La Jolla, CA 92037 Phone: (858) 784-8820 Email: [email protected]

Education/Training

9/2005 – 8/2009 Skirball Institute at NYU Medical School New York, NY NIH Postdoctoral Research Fellow

7/2001 – 8/2005 The Scripps Research Institute La Jolla, CA Ph.D. Chemistry

9/1997 – 5/2001 The University of Virginia Charlottesville, VA B.Sc. Chemistry

Positions/Employment

12/2016 – present The Scripps Research Institute La Jolla, CA Associate Professor (tenured)

8/2009 – 12/2016 The Scripps Research Institute La Jolla, CA Assistant Professor

9/2005 – 8/2009 Skirball Institute at NYU Medical School New York, NY NIH Postdoctoral Research Fellow; Advisor – David Ron

7/2001 – 8/2005 The Scripps Research Institute La Jolla, CA Graduate Research Associate; Advisor – Jeffery W. Kelly

8/2000 – 5/2001 University of Virginia Charlottesville, VA Undergraduate Research Associate; Advisor – Milton Brown

9/1999 – 7/2000 University of Virginia Charlottesville, VA Undergraduate Research Associate; Advisor – Felicia Etzkorn

5/1999 – 8/1999 Cornell University (REU Program) Ithaca, NY Undergraduate Research Associate; Advisor – David Zax

Teaching Experience

Wiseman CV

2017-present The Scripps Research Institute La Jolla, CA Lecturer – Chemical Biology I

2014-present The Scripps Research Institute La Jolla, CA Course Organizer – Cell Biology

2012-present The Scripps Research Institute La Jolla, CA Lecturer – Structural Biology

2011 – present The Scripps Research Institute La Jolla, CA (every 2 yrs) Course Organizer – Protein Folding in the Cell

2010-2016 The Scripps Research Institute La Jolla, CA (every 3 yrs) Course Co-Organizer – Chemical Biology I

2012-2013 The Scripps Research Institute La Jolla, CA Lecturer – Cell Biology

2004 The Scripps Research Institute La Jolla, CA Graduate Teaching Assistant – Bioorganic Chemistry I

Other Committees Served

2019-present Member TSRI Genomics Core Faculty Advisory Committee 2018-present Member of the TSRI Presidential Planning Committee 2018-present Member Outreach, Inclusion, Committee Engagement Committee 2018-present Member Research Training Committee 2017-present Co-organizer of the Mesa-Wide ER stress club 2016-present Member TSRI Graduate Student Admissions Committee 2016-present Member Molecular Medicine Departmental Seminar Series Committee 2009-present Chair or member of >20 TSRI graduate student thesis committees 2012-2016 Co-organizer of TSRI Junior Faculty Luncheon

Awards/Honors

Glenn Award for Research in Biological Mechanisms of Aging, 2017 Amyloidosis Foundation Jr. Research Grant Award, 2014 Ellison Medical Foundation New Scholar Award in Aging, 2011 NRSA Kirschstein Postdoctoral Research Fellowship, 2006 Norton B. Gilula Graduate Fellowship, The Scripps Research Institute, 2004 Fletcher Jones Foundation Graduate Fellowship, The Scripps Research Institute, 2003 Oscar R. Rodig Award for Chemical Excellence, University of Virginia, 2001 Graduated with Highest Distinction, University of Virginia, 2001 Dean’s List, University of Virginia, 1998-2001

Wiseman CV

Intermediate Honors, University of Virginia, 2000 Research Experience for Undergraduates, National Science Foundation, 1999

Peer-Reviewed Publications (2013-present)

Puchades, C; Ding, B; Song, A; Wiseman, RL; Lander, GC; Glynn, SE (2019) Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveals the Molecular Basis for Activity in Health and Disease (2019) Mol Cell, in press (PMID: 31327635).

Plate, L; Rius, B; Nguyen, B; Genereux, JC; Kelly, JW; Wiseman, RL (2019) Quantitative Interactome Proteomics Reveals a Molecular Basis for ATF6-Dependent Regulation of a Destabilized, Amyloidogenic Protein, Cell Chem Biol, in press (PMID: 31105062)

Carreras-Sureda, A; Jana, F; Ramos-Fernandex, E; Urra, H; van Vliet, AR; Durand, S; Mortensen, DE; Pihan, P; Gonzalez-Quirez, M; Saredo, A; Bustos, G; Vincente, R; Inestrosa, NC; Wiseman, RL; Agonstinis, A; Bultynck, G; Court, F; Kroemer, G; Cesar- Cardenas, J; Hetz, C (2019) Non-Canonical Function of the Unfolded Protein Response Sensor IRE1α as a Structural Determinant of Mitochondrial-Associated ER Membranes, Nat Cell Biol, in press (PMID: 31110288)

Grandjean, JMD; Plate, L; Morimoto, RI; Bollong, MJ; Powers, ET; Wiseman, RL (2019) Deconvoluting Stress-Responsive Signaling Pathway for Pharmacologic Activation Using Targeting RNA-Sequencing, ACS Chemical Biology, in press (PMID: 30821954).

Blackwood, EA; Azizi, K; Thuerauf, DJ; Paxman, RJ; Plate, L; Kelly, JW; Wiseman, RL; Glembotski, CC (2018) Pharmacologic ATF6 Activation Confers Global Protection in Widespread Disease Models by Reprogramming Cellular Proteostasis, Nature Communications, 10, 187-195 (PMID: 30643122).

Romine, IC; Wiseman, RL (2018) PERK Regulates Extracellular Proteostasis of an Amyloidogenic Protein, Sci Rep, 9, 410-414 (PMID: 30675021).

Paxman, RJ; Plate, L; Blackwood; EA; Glembotski, CC; Powers, ET; Wiseman, RL*; Kelly, JW* (2018) A Small Molecule that Preferentially Activates the ATF6 Pathway of the Unfolded Protein Response is Metabolically Activated to Selectively Modify Endoplasmic Reticulum Proteins, ELIFE, in press (PMID: 30084354).

Giadone, RM; Rosarda, JD; Reddy Akepati, P; Thomas, AC; Boldvbataar, B; James, MF; Wilson, AA; Sanchorawala, V; Connors, LH; Berk, JL; Wiseman, RL; Murphy, GJ (2018) A genetically diverse library of ATTR patient-specific induced pluripotent stem cells for disease modeling and in vitro testing of novel therapeutics, Amyloid, in press (PMID: 30032658).

Wiseman CV

Cole, KS; Grandjean, JMD; Chen, K; Witt, CH; O’Day, J; Shoulders, MD; Wiseman, RL; Weerapana, E (2018) Characterization of an A-Site Selective Protein Disulfide Isomerase A1 Inhibitor, Biochemistry, 57, 2035-2043 (PMID: 29521097).

Lebeau, J; Saunders, JM; Moraes, VWR; Madhavan, A; Madrazo, N; Anthony, MC; Wiseman RL (2018) The PERK Arm of the Unfolded Protein Response Regulates Mitochondrial Morphology During Acute Endoplasmic Reticulum Stress, Cell Reports, 22, 2827-2836 (PMID: 295394013).

Kroeger, H; Grimsey, N; Paxman, R; Plate, L; Jones, Y; Shaw, PX; Trejo, J; Tsang, SH; Powers, ET; Kelly, JW; Wiseman, RL; Lin, JH (2018) The Unfolded Protein Response Regulator ATF6 Promotes Mesodermal Differentiation, Science Signaling, in press (PMID: 29440509).

Puchades, C; Rampello, AJ; Giuliano, CJ; Shin, M; Wiseman, RL; Glynn, SE; Lander GC (2017) Structure of the Mitochondrial Inner Membrane AAA+ Protease YME1 Reveals the Mechanism of Substrate Processing, Science, in press (PMID: 29097521).

Chen, KC; Qu, S; Chowdhury, S; Noxon, IC; Schonhoft, JD; Plate, L; Powers, ET; Kelly, JW; Lander, GC; Wiseman, RL (2017) The Endoplasmic Reticulum HSP40 Co- chaperone ERdj3/DNAJB11 Assembles and Functions as a Tetramer, EMBO J, 36, 2296-2309 (PMID: 28655754).

Chen, JJ; Genereux, JC; Suh, EH; Vartabedian, VF; Rius, B; Qu, S; Dendle, MTA; Kelly, JW; Wiseman, RL (2016) Endoplasmic Reticulum Proteostasis Influences the Oligomeric State of an Amyloidogenic Protein Secreted from Mammalian Cells, Cell Chemical Biology, 23, 1282-1293 (PMID: 27720586).

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 (PMID: 27435961). *Co-corresponding authors.

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 (PMID: 26923599).

Murray, AN; Chen, W; Antonopoulos, A; Hanson, SR; Wiseman, RL; Dell, A; Haslam, SM; Powers, DL; Powers, ET; Kelly, JW (2015) Enhanced Aromatic Sequons Increase Oligosaccharyltransferase Glycosylation Efficiency and Glycan Homogeneity, Chemistry & Biology, 22, 1052-1062 (PMID: 26190824).

Baranczak, A; Liu, Yu; Connelly, Stephen; Han Du, W; Greiner, ER; Wiseman, RL; Eisele, YS; Bradbury, NC; Dong, J; Sharpless, KB; Noodleman, L; Wilson, IA; Encalada,

Wiseman CV

SE; Kelly, JW (2015) A Fluorogenic Arylfluorosulfate for Intraorganellar Transthyretin Imaging in Living Cells and in C. elegans, J. Am. Chem. Soc., 137, 7404-7414 (PMID: 26051248).

Rainbolt, TK; Saunders, JM; Wiseman RL (2015) YME1L Degradation Reduces Mitochondrial Proteolytic Capacity During Oxidative Stress, EMBO Reports, 16, 97-106 (PMID: 25433032).

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 (PMID: 25361606). F1000 recommended.

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 (PMID: 25444553).

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 (PMID: 25157167).

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 (PMID: 24689980).

Rappley, I; Monteiro, C; Novais, M; Baranczak, A; Solis, G; Wiseman, RL; Helmke, S; Maurer, MS; Coelho, T; Powers, ET; Kelly, JW (2014) Quantification of Transthyretin Kinetic Stability in Human Plasma Using Subunit Exchange, Biochemistry, 53, 1993- 2006 (PMID: 24661308).

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 (PMID: 24315374).

Leung, A; Nah, SK.; Reid, W; Ebata, A; Koch, CM; Monti, S; Genereux, JC; Wiseman, RL; Wolozin, B; Connors, LH; Berk, JL; Seldin, DC; Mostoslavsky, G; Kotton, DN; Murphy, GJ (2013) Induced Pluripotent Stem Cell Modeling of Multisystemic, Hereditary Transthyretin Amyloidosis, Stem Cell Reports, 1, 451-463 (PMID: 24286032). F1000 recommended.

Shoulders, MD; Ryno, LM; Cooley, CB; Kelly, JW; Wiseman, RL (2013) Broadly Applicable Methodology for the Rapid and Dosable Small Molecule-Mediated

Wiseman CV

Regulation of Transcription Factors in Human Cells, J. Am. Chem. Soc., 135, 8129- 8135 (PMID: 23682758).

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 (PMID: 23583182).

Preprints (2016-present)

Noxon, IC; Wiseman, RL (2018) PERK Signaling Regulates Extracellular Proteostasis of an Amyloidogenic Protein, bioRXIV, (https://doi.org/10.1101/419564).

Plate, L; Rius, B; Nguyen, B; Genereux, JC; Kelly, JW; Wiseman, RL (2018) Quantitative Interactome Proteomics Reveals a Molecular Basis for ATF6-Dependent Regulation of a Destabilized, Amyloidogenic Protein, bioRXIV, (https://doi.org/10.1101/381525).

Giadone, RM; Liberti, DC; Matte, TM; Skvir, N; Chen, KC; Jean, JC; Wilson, AA; Kotton, DN; Wiseman, RL; Murphy, GJ (2018) Defining Hepatic Modifiers of ATTR Amyloidosis Through Therapeutic Gene Editing in Patient iPSCs, bioRXIV, (https://doi.org/10.1101/358515)

Puchades, C; Rampello, AJ; Giuliano, CJ; Shin, M; Wiseman, RL; Glynn, SE; Lander GC (2017) Atomic Structure of the Mitochondrial Inner Membrane AAA+ Protease YME1 Reveals the Mechanism of Substrate Processing, bioRXIV, (https://doi.org/10.1101/189316).

Published Reviews/Commentaries/Book Chapters (2013-present)

Glembotski, CC; Rosarda, JD; Wiseman, RL (2019) Proteostasis and Beyond: ATF6 in Ischemic Disease, Trends in Mol Med, in press. (PMID: 31078432)

Wiseman, RL (2019) Lining Up for Quality Control: Linear Ubiquitin and Proteotoxicity, EMBO J, in press (PMID: 30975687).

Wiseman CV

Lebeau, J; Rainbolt, TK; Wiseman, RL (2018) Coordinating Mitochondrial Biology Through the Stress-Responsive Regulation of Mitochondrial Proteases, International Reviews in Cellular and Molecular Biology, in press (PMID: 30072094).

Plate, L; Wiseman, RL (2017) Regulating Secretory Proteostasis Through the Unfolded Protein Response: From Function to Therapy, Trends in Cell Biology, in press (PMID: 28647092).

Plate, L; Paxman, RJ; Wiseman, RL*, Kelly JW* (2016) Modulating protein quality control, eLIFE, in press (PMID: 27435959).

Lindberg, I; Shorter, J; Wiseman, RL; Chiti, F; Dickey, CA; McLean PJ (2015) Chaperones and Neurodegeneration, J. Neuroscience, 35, 13853-13859 (PMID: 26468185).

Chen, JJ; Genereux, JC; Wiseman, RL (2015) Endoplasmic Reticulum Quality Control and Systemic Amyloid Disease: Impacting Protein Stability from the Inside Out, invited review to IUBMB Life, 67, 404-413 (PMID: 26018985).

Genereux, JC; Wiseman, RL (2015) Regulating Extracellular Proteostasis Capacity Through the Unfolded Protein Response, invited Extra-View Perspective to Prion, 9, 10- 21 (PMID: 25946012).

Eisele, YS; Monteiro, C; Fearns, C; Encalada, SE; Wiseman, RL; Powers, ET; Kelly, JW (2015) Targeting Protein Aggregation in the Treatment of Degenerative Diseases, invited review to Nature Rev and Drug Discovery, in press (PMID: 26338154).

Rainbolt, TK; Saunders, JM; Wiseman RL (2014) Stress-Responsive Adaptation of Mitochondria Through the ER Unfolded Protein Response, invited Review to Trends in Endocrinology & Metabolism, 25, 528-537 (PMID: 25048297).

Ryno, LM; Wiseman, RL; Kelly, JW (2013) Targeting Unfolded Protein Response Signaling Pathways to Ameliorate Protein Misfolding Diseases, invited Review to Curr. Opin. Chem. Biol, 17, 346-352 (PMID: 23647985). Co-corresponding author.

Patents

Cooley, C; Kelly, JW; Paxman, R; Plate, L; Wiseman, RL (2016) Regulators of the Endoplasmic Reticulum Proteostasis Network, Application number: WO2017117430A1.

Ron, D; Sicheri, F; Harding, H; Wiseman, RL; Zhang, Y; Lee K (2011) Method of modulating Ire1 activity, Application number: WO2011041557A1.

Wiseman CV

Presentations at Professional Conferences/Invited Lectures (2016-present)

Wiseman, RL A Little Goes a Long Way: Pharmacologically Targeting the UPR for Neuronal Protection. Invited Lecture at the International Symposium on Neurodegenerative Disease at UT-Southwestern, Dallas, TX, Oct 25th, 2019.

Wiseman, RL A Little Goes a Long Way: Pharmacologically Targeting the UPR for Etiologically Diverse Diseases. Invited Lecture at the Oslo ER Proteostasis Symposium, Oslo, Norway, Oct 14th, 2019.

Wiseman, RL The Source of the Problem: Endoplasmic Reticulum Proteostasis and Systemic Amyloid Disease, Invited Lecture at the Colorado Protein Stability Meeting, Breckenridge, CO, July 30th, 2019.

Wiseman, RL Repurposing before Screening: Targeting UPR Signaling Pathways for Etiologically-Diverse Diseases, Invited Lecture at Gordon Conference on Stress Proteins, Il Cicco, Italy June 26th, 2019.

Wiseman, RL The Source of the Problem: Endoplasmic Reticulum Proteostasis and Systemic Amyloid Disease, Invited Lecture at the FASEB Meeting on Protein Aggregation, Snowmass, CO, June 12th, 2019.

Wiseman, RL Lost in Translation: Proteolytic Remodeling of the Mitochondrial Proteome Through the Unfolded Protein Response, Invited Lecture at Calico, June 4th, 2019.

Wiseman, RL Unfolded Protein Response & Mitochondrial Regulation, Invited Lecture Presented at the Gordon Conference on Mitochondria in Health and Disease, Ventura, CA, March 20th, 2019.

Wiseman, RL Repurposing before Screening: Targeting Biological Nodes for Etiologically Diverse Diseases, Invited Lecture Presented at University of Alabama, Birmingham, Dec 11th, 2018.

Wiseman, RL Unexpected Outcomes: Non-secretory functions of the unfolded protein response, Invited Lecture Presented at Frankfurt University Medical School, Sept 21st, 2018.

Wiseman, RL Unexpected Outcomes: Non-secretory functions of the unfolded protein response, Invited Lecture Presented at Heidelberg University, ZMBH, Sept 18th, 2018.

Wiseman, RL Correcting Proteostasis Defects Through Pharmacologic Activation of the Unfolded Protein Response Associated Transcription Factor ATF6, Lecture Presented at the Cold Spring Harbor Meeting on Protein Homeostasis, April 17-22, 2018.

Wiseman, RL Therapeutic Targeting of the Unfolded Protein Response to Treat Disease; Lecture Presented at the Society for Laboratory Automation and Screening

Wiseman CV

National Meeting, Feb 6th, 2018.

Wiseman, RL Therapeutic Targeting of the Unfolded Protein Response to Treat Disease; Lecture Presented at The University of Pittsburgh, Jan 24th, 2018.

Wiseman, RL Coordinating Proteostasis Environments Through the Unfolded Protein Response; Lecture Presented at the Morgridge Institute, University of Wisconsin- Madison, Nov 15th, 2017.

Wiseman, RL Coordinating Proteostasis Environments Through the Unfolded Protein Response; Lecture Presented at Indiana University School of Medicine, Oct 10th, 2017.

Wiseman, RL Stress-responsive Regulation of Mitochondria Proteostasis: A Structural Perspective, Lecture Presented at the EMBO Workshop on Mitochondria Quality Control; July 2-5th; Xi’an, China.

Wiseman, RL Unfolded Protein Response-Dependent Regulation of Secretory Proteostasis, Lecture Presented at the FASEB Meeting on Protein Aggregation in Health and Disease, June 11-16th, 2017; Steamboat Springs, CO.

Wiseman, RL Stress-Responsive Regulation of Mitochondria Inner Membrane Proteostasis, Lecture Presented at the Keystone Symposium on Mitochondria, Metabolism and Heart Failure, May 8th-12th, 2017; Santa Fe, NM.

Wiseman, RL Targeting the Unfolded Protein Response for Systemic Amyloid Diseases, Lecture Presented at The University of Pittsburgh Medical Center, March 22nd, 2017.

Wiseman, RL Regulating Secretory Proteostasis Through the Unfolded Protein Response, Lecture Presented at the Keystone Symposium on Cellular Stress Responses and Infectious Agents, Dec 4th-8th, 2016; Santa Fe, NM.

Wiseman, RL Coordinating Proteostasis Environments Through the Unfolded Protein Response, Lecture presented at Johns Hopkins University Medical School, Nov 2nd, 2016.

Wiseman, RL Coordinating Proteostasis Environments Through the Unfolded Protein Response, Lecture presented at the 2016 Nobel Forum: Unfolded Proteins: From Benchtop to Bedside, Sept. 4th-7th, 2016; Stockholm, Sweden.

Wiseman, RL Reciprocal Regulation of Mitochondrial Inner Membrane Proteases Adapts Mitochondrial Proteostasis During Stress, Lecture presented at the Cold Spring Harbor Meeting on Protein Homeostasis in Health & Disease, April 18-22nd, 2016; Cold Spring Harbor, NY.

Wiseman, RL Proteotoxicity and the Unfolded Protein Response, Lecture Presented for

Wiseman CV

the American Society for Investigative Pathology Annual Meeting at Experimental Biology 2016, April 1-5, 2016; San Diego, CA.

Professional Societies

American Chemical Society American Society for Cell Biology American Society for Biochemistry and Molecular Biology Society for Neuroscience American Society for Investigative Pathology

Journals Served as Editorial Advisory Board

Life Science Alliance

Journals/Foundations Served as an ad hoc Reviewer

Cell, Science, Nature, Cell Chemical Biology, Molecular Cell, Cell Reports, Science Signaling, Nature Cell Biology, Nature Chemical Biology, Nature Communications, Nature Neuroscience, Scientific Reports, EMBO J, EMBO Reports, ELIFE, PLOS Biology, PLOS Genetics, PNAS, J. Cell Biology, JACS, ACS Chemical Biology, Structure, FASEB, Aging Cell, etc.

Alzheimer’s Association, French National Cancer Institute, Swiss Science Foundation Review, Cancer UK, MRC, Telethon, Cottrell Scholar Award, National Science and Research Council of Canada, Welcome Trust, etc

NIH Study Sections Served:

Cellular Mechanisms of Neurodegenerative Disease (CMND): Member 2019-present. Cellular Mechanisms of Neurodegenerative Disease (CMND): Ad hoc June 7-8th, 2018. Hepatobilliary Pathophysiology (HBPP): Ad hoc Feb 13-14th, 2012

Research Support

Active Research Support

R01AG046495 (PI: Kelly & Wiseman) 04/01/18 – 03/31/22 NIH/NIA Discovering Small Molecule Activators of Stress Responsive Signaling This project uses high-throughput screening and genetic approaches to identify and characterize selective small molecule activators of stress-responsive signaling pathways involved in regulating cellular protein homeostasis (e.g. the Heat-Shock

Wiseman CV

Response, the Unfolded Protein Response, etc). Role: PI (Multi-PI grant)

R01DK107604 (PI: Wiseman) 04/01/16 – 03/31/20 NIH/NIDDK Establishing Strategies to Ameliorate Amyloid Pathology in Light Chain Amyloidosis This project establishes new therapeutic approaches to reduce the proteotoxic extracellular aggregation and deposition of destabilized immunoglobulin light chains currently limiting the treatment of Light Chain Amyloidosis patients. Role: PI

R01NS095892 (PI: Wiseman) 04/01/16 – 03/31/21 NIH/NINDS Impacting Mitochondria Function Through Altered Protease Activity This project defines the differential stress-sensitivity of the mitochondrial inner membrane proteases YME1L and OMA1 and the implications of stress-induced alterations in the activity of these proteases on mitochondria function, morphology and cell survival. Role: PI

R01NS092829 (PI: Wiseman) 07/01/15 – 06/30/20 NIH/NINDS Direct Regulation of Extracellular Proteostasis by the Unfolded Protein Response The primary focus of this project is to elucidate the functional impact of the secreted, stress-inducible co-chaperone ERdj3 on the maintenance and stability of the extracellular proteome. This project is an R01 level continuation of my funded R21NS079882. Role: PI

R21AG061697 (PI: Lander) 02/01/19 – 12/31/20 NIH/NIA Defining the Molecular Mechanisms Underlying Mitochondrial Proteostasis This grant used cryo-electron microscopy (cryo-EM) to define the structure and mechanism of mitochondrial proteases important for regulating mitochondrial proteostasis. Role: co-I

DISC2-10973 (PI: Lin, UCSD) 02/01/19-01/31/21 CIRM Small Molecule Proteostasis Regulators to Treat Photoreceptor Disease This collaborative grant defines the therapeutic potential of small molecule proteostasis regulators for their ability to mitigate pathology in diseases of the retina. Role: Co-I

Pending Research Support

Wiseman CV

R01DK107604 (PI: Wiseman) 04/01/20 – 03/31/25 NIH/NIDDK Establishing Strategies to Ameliorate Amyloid Pathology in Light Chain Amyloidosis This project is a competitive renewal that establishes new therapeutic approaches to reduce the proteotoxic extracellular aggregation and deposition of destabilized immunoglobulin light chains currently limiting the treatment of Light Chain Amyloidosis patients. Role: PI

R01DK123038 (PI: Wiseman & Murphy) 08/01/14-06/30/18 NIH/NIDDK Understanding Hepatic Proteostasis in Systemic Amyloid Diseases This project focuses on defining the implications of the liver in dictating the extracellular aggregation and distal toxicity of amyloidogenic proteins implicated in systemic amyloid diseases. Role: PI (Multi-PI Grant with George Murphy at BU Medical School)

R01NS115801 (PI: Wiseman) 04/01/20 – 03/31/25 NIH/NINDS Unfolded Protein Response-Dependent Protection from Ischemic Stroke This project defines the specific contributions of protective UPR signaling through the ATF6 pathway in protecting neurons against I/R-associated insults. Role: PI

Recent Completed Research Support

R01DK102635 (PI: Wiseman & Murphy) 08/01/14-06/30/18 NIH/NIDDK Targeting Endogenous Signaling Pathways to Ameliorate Systemic Amyloidoses This project uses ligand-regulated UPR-associated transcription factors to demonstrate the therapeutic potential for stress-independent activation of UPR signaling pathways to ameliorate the secretion and extracellular proteotoxicity of destabilized, amyloidogenic variants of transthyretin (TTR). Role: PI (Multi-PI Grant with George Murphy at BU Medical School)

R01AG046495 (PI: Kelly) 04/01/13 – 03/31/18 NIH/NIA Discovering Small Molecule Activators of Stress Responsive Signaling This project uses high-throughput screening and genetic approaches to identify and characterize selective small molecule activators of stress-responsive signaling pathways involved in regulating cellular protein homeostasis (e.g. the Heat-Shock Response, the Unfolded Protein Response, etc). Role: co-PI