Press Release: May 2018
Dr. Scott A. Oakes is the 2019 recipient of the American Society for Investigative Pathology (ASIP) Outstanding Investigator Award. This prestigious award recognizes mid-career investigators who have demonstrated excellence in experimental pathology research.
Dr. Oakes is a cell biologist, board certified anatomic pathologist, and tenured Professor of Pathology at the University of California, San Francisco (UCSF), where he directs the Oakes Laboratory and serves as an attending physician on the autopsy service.
It was during a postdoctoral research fellowship at the Dana-Farber Cancer Institute in the laboratory of the late Dr. Stanley J. Korsmeyer, a leading authority on apoptosis, that Dr. Oakes developed an interest in cellular responses to misfolded proteins and endoplasmic reticulum (ER) stress.
When Dr. Oakes established his own laboratory at UCSF in 2005, he continued to build on the work he had begun in the Korsmeyer lab. He and his associates made a series of significant discoveries, including elucidation of the molecular events that control cell fate under conditions of ER stress via the Unfolded Protein Response (UPR). Dr. Oakes and his longtime collaborator Dr. Feroz Papa, Professor of Medicine at UCSF and Director of the Papa Laboratory, discovered that in response to ER stress signals, IRE1α (Inositol requiring enzyme 1 alpha), a kinase/endoribonuclease (RNase), acts as a critical life-or-death switch, promoting either adaptation or apoptosis depending on the degree of stress. Moreover, according to Dr. Andrew Lichtman, Professor of Pathology at Harvard Medical School, Drs. Oakes and Papa learned how to “tune” the life-death outputs of IRE1α using kinase inhibitors – a major breakthrough with important implications for many degenerative diseases. Dr. Oakes and his collaborators subsequently invented a novel class of IRE1α inhibitors called Kinase Inhibiting RNase Attenuators (KIRAs) that preserve cell viability and function when responding to ER stress.
Dr. Oakes’ laboratory continues to focus on the biology and treatment of Protein Folding Disorders (PFD), specifically: how protein misfolding in the ER triggers cell dysfunction and pathological cell loss seen in human degenerative diseases like Alzheimer’s, Amyotrophic Lateral Sclerosis (ALS), Parkinson’s disease, type 2 diabetes, retinal degeneration and liver cirrhosis; how cells sense internal damage, determine degree of damage and whether to communicate a death signal to mitochondrial apoptotic components; development of biomarkers and therapeutic tools (genetic, chemical-genetic and pharmacological) to manipulate the Unfolded Protein Response (UPR) master regulators in cancer cells to enhance survival rate; and translating mechanistic knowledge of cell response to ER stress into new therapies for patients with PFDs.
In addition to biomedical research, Dr. Oakes devotes substantial time to teaching, mentoring, advising, and service activities. He currently serves as Director of Student Mentoring for the Biomedical Sciences (BMS) graduate program at UCSF and oversees the pairing and mentoring of approximately 170 students. In addition, he supervises and teaches graduate students and postdoctoral fellows in his research laboratory. He spends six weeks each year on UCSF’s Autopsy Service, during which he supervises and instructs residents and medical students on the pathophysiology of disease in patients undergoing necropsy. He is Director of the Physician Scientist Pathway, an initiative for which Dr. Oakes selects and mentors three to four research-focused residents each year and facilitates their transition to laboratory-based postdoctoral training. He is also an active member of the Admissions Committee for the UCSF residency program and helps run several pathology laboratory sections for the medical school’s immunology course. In August 2016, UCSF launched the Bridges Curriculum, a fully integrated 45-month medical school curriculum that utilizes the element of Inquiry as one of its core components. Dr. Oakes spent a significant amount of time and effort developing the Inquiry component, which exposes first, second and third-year medical students to the range of biomedical research at UCSF. In 2015, Dr. Oakes was named Director of the Inquiry Immersion component, a two-week block of time in each of the four years of medical school during which students focus on didactics and project development related to areas of inquiry and topics of interest.
Dr. Oakes earned his BA in Biochemistry in 1993 from Elmira College in New York, then attended medical school at the University of Connecticut from 1993 to 1998. While in medical school, Dr. Oakes chose to spend a year in the laboratory of Dr. John O'Shea at the NIH as an HHMI (Howard Hughes Medical Institute) Scholar studying the JAK-STAT signal transduction pathway. That same year, he published a first author paper in Immunity and was coauthor on four other papers. In 1998, after receiving his MD, he entered residency training in anatomic pathology at Harvard’s Brigham and Women's Hospital, under the chairmanship of Dr. Ramzi Cotran. In 2000, Dr. Oakes entered a research fellowship at Dana-Farber Cancer Institute, which he completed in 2005, after which he was recruited to UCSF as Assistant Professor of Pathology. He was promoted to Associate Professor in 2012, and to Professor four years later.
Dr. Oakes is the author or coauthor of over 40 peer-reviewed articles and a successful grantee with ten current awards, seven of which list him as Principal Investigator or Co-Investigator. He is listed as one of six inventors on an international patent application for Modulation of IRE1, novel ATP-competitive small molecule kinase inhibitors of IRE1a that prevent oligomerization and/or allosterically inhibit RNase activity, and on a second patent application for Combination Therapy against IRE1.
In the words of Dr. Abul K. Abbas, Professor and Chair of the Department of Pathology at UCSF:
Scott Oakes is a spectacularly successful experimental pathologist who brings an impressive level of sophistication to basic problems of cell injury. He is the quintessential physician-scientist and has established a leading research program that is now translating their discoveries about the mechanisms of cell degeneration into small molecule therapies. On the basis of his exceptional research, teaching, and leadership activities in the field of pathology, I believe that Dr. Scott Oakes is highly deserving of the 2019 ASIP Outstanding Investigator Award.
Dr. Oakes will receive the Outstanding Investigator Award at the 2018 PISA Meeting in Ann Arbor, Michigan on Sunday, October 21 from 3:30 PM to 4:10 PM, where he will present an award lecture, “The Unfolded Protein Response: Cancer Friend or Foe?”
For additional information on PISA2018, including the preliminary program, hotel information, and upcoming deadlines, please go to