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Research and Clinical Interests

Protein Misfolding, Endoplasmic Reticulum Stress and Disease

Our laboratory is breaking new ground in discovering how various forms of damage trigger death in normal cells and what goes wrong with this process in diseases such as neurodegeneration and cancer—in the hopes of finding new therapeutic targets through which to control the cell’s decision to live or die. Mounting evidence suggests that apoptosis triggered by excessive stress on the protein folding capacity of the endoplasmic reticulum (ER) contributes to pathological cell loss in many common human degenerative diseases, including Alzheimer’s, Parkinson’s, Amyotrophic Lateral Sclerosis, type 2 diabetes, and liver cirrhosis. Moreover, highly secretory cancers such as multiple myeloma have evolved mechanisms to evade the normally cytotoxic consequences of ER stress. My long-term goals are to understand how apoptosis is regulated in these diseases and to develop strategies to target this pathway for therapeutic benefit. Our laboratory has designed rigorous in vitro assays to detect and isolate several novel apoptotic signals and is tracing them all the way back to the stress sensor proteins at the ER. We are currently designing pharmacological interventions to precisely control and tune these signaling switches with small molecules to influence cell survival.

Selected Publications

• Reyes NA, Fisher JK, Austgen K, VandenBerg S, Huang EJ, and Oakes SA. Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis. 2010. J. Clin. Invest. 120(10):3673-3679.
• Dan D, Lerner AG, Vande Walle L, Upton JP, Xu W, Hagen A, Backes BJ, Oakes SA, Papa FR. IRE1alpa kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell. 2009;138:562-575.
• Upton JP, Austgen K, Nishino M, Coakley KM, Hagen A, Han D, Papa FR, Oakes SA. Caspase-2 cleavage of BID is a critical apoptotic signal downstream of endoplasmic reticulum stress. Mol Cell Biiol. 2008;28(12):3943-3951.
• Han D, Upton JP, Hagen A, Callahan J, Oakes SA, Papa FR. A kinase inhibitor activates the IRE1alpha RNase to confer cytoprotection against ER stress. Biochem. Biophys. Res. Commun. 2008;365:777-783.
• Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T, Korsmeyer SJ. Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA. 2005;102:105-110.
• Scorrano L*, Oakes SA*, Opferman JT, Cheng EH, Sorcinelli MD, Pozza T, Korsmeyer SJ. BAX and BAK regulation of endoplasmic reticulum Ca2+:a control point for apoptosis. Science 2003;300:135-139. *These authors contributed equally.

Selected Awards

• 2000-2003: NIH Pathology Training Grant Recipient
• 2003-2008: NIH Mentored Clinical Scientist Development Award (K08)
• 2006-2007: American Cancer Society Junior Investigator Award
• 2007-2011: HHMI Early Career Physician Scientist Award

Additional Information

• Detailed CV

• Associate Professor of Pathology
• Pathology
• Research and Autopsy

Specialty Area

Autopsy

Contact Information

• scott.oakes@ucsf.edu
• Phone: (415) 476-1777
• Pager: (415) 443-9454
• Fax: (415) 514-3165

• UCSF Department of Pathology
• 513 Parnassus Avenue
• Room HSW-517, Box 0511
• San Francisco, CA 94143-0511

Web Site

• http://pathology.ucsf.edu/oakes/

Other UCSF Organizational Association(s)

Member

• UCSF Helen Diller Family Comprehensive Cancer Center
• Biomedical Sciences (BMS) Graduate Program

Hospital Affiliation(s)

• Moffitt-Long