Paul S. Mischel (born July 13, 1962) is an American physician-scientist whose laboratory has made pioneering discoveries in the pathogenesis of human cancer. He is currently a Professor and Vice Chair of Research for the Department of Pathology and Institute Scholar of ChEM-H,

Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is consider ...

. Mischel was elected into the

American Society for Clinical Investigation The American Society for Clinical Investigation (ASCI), established in 1908, is one of the oldest and most respected medical honor societies in the United States. Organization and purpose The ASCI is an honorary society to which more than 2,800 ph ...

(ASCI), serving as ASCI president in 2010/11. He was inducted into the

Association of American Physicians The Association of American Physicians (AAP) is an honorary medical society founded in 1885 by the Canadian physician Sir William Osler and six other distinguished physicians of his era for "the advancement of scientific and practical medicine." ...

, and was elected as a fellow of the

American Association for the Advancement of Science The American Association for the Advancement of Science (AAAS) is an American international non-profit organization with the stated goals of promoting cooperation among scientists, defending scientific freedom, encouraging scientific respons ...

Career

Mischel was born on July 13, 1962. After losing his father to cancer, he became committed to a career in cancer research. He attended the

University of Pennsylvania The University of Pennsylvania (also known as Penn or UPenn) is a private research university in Philadelphia. It is the fourth-oldest institution of higher education in the United States and is ranked among the highest-regarded universitie ...

and received his M.D. from

Cornell University Medical College The Joan & Sanford I. Weill Medical College of Cornell University is Cornell University's biomedical research unit and medical school located in Upper East Side, Manhattan, New York City, New York. Weill Cornell Medicine is affiliated with New ...

in 1991, graduating

Alpha Omega Alpha Alpha Omega Alpha Honor Medical Society () is an honor society in the field of medicine. Alpha Omega Alpha currently has active Chapters in 132 LCME- accredited medical schools in the United States and Lebanon. It annually elects over 4,000 new ...

. Mischel completed residency training in Anatomic Pathology and Neuropathology at

UCLA The University of California, Los Angeles (UCLA) is a public land-grant research university in Los Angeles, California. UCLA's academic roots were established in 1881 as a teachers college then known as the southern branch of the California St ...

, followed by post-doctoral research training with Louis Reichardt at

HHMI The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization based in Chevy Chase, Maryland. It was founded in 1953 by Howard Hughes, an American business magnate, investor, record-setting pilot, engineer, fil ...

UCSF The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It condu ...

. Mischel joined the faculty of

in 1998. In August 2012, he was recruited to the

Ludwig Institute for Cancer Research Ludwig Cancer Research is an international community of scientists focused on cancer research, with the goal of preventing and controlling cancer. It encompasses the Ludwig Institute for Cancer Research, an international non-profit organization f ...

, San Diego and

UCSD The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Insti ...

. In 2021, he joined Stanford University School of Medicine, where he currently serves as a Professor and Vice Chair of Research for the Department of Pathology and Institute Scholar of ChEM-H.

Research

Mischel’s work bridges cancer genetics, signal transduction and cellular metabolism in the pathogenesis of human cancer.

Extrachromosomal oncogene amplification

Mischel found that tumors can dynamically change in response to changing environments at a rate that cannot be explained by classical genetics. Prior to 2017, extrachromosomal DNA was thought to be a rare, but interesting event in cancer (1.4% of tumors), of unclear biological significance. Mischel and colleagues integrated whole genome sequencing, cytogenetics and structural modeling to accurately and globally quantify extrachromosomal oncogene amplification, measure its diversity, map its contents, and study its biochemical regulation. They demonstrated widespread extrachromosomal oncogene amplification across many cancer types, showed that it potently drives tumor evolution and drug resistance, and identified specific signaling, biochemical and metabolic mechanisms that control its copy number and activity in response to changing environmental conditions. This ground-breaking work challenges existing chromosomal maps of cancer, provides new insights into the mechanisms controlling the level, location and activity of amplified oncogenes, and yields new paradigms in the genotype-environment interactions that promote cancer progression and drug resistance.

Metabolic co-dependency pathways in cancer

Integrating mechanistic studies with analyses of tumor tissue from patients treated in clinical trials, Mischel and colleagues discovered signaling, transcriptional, and metabolic co-dependencies that are downstream consequences of oncogene amplification, including alterations in glucose and lipid metabolism that drive tumor growth, progression and drug resistance. These studies, focused primarily on the highly lethal brain cancer,

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

, resulted in new understandings of the fundamental metabolic processes by which oncogene amplification drives cancer progression and drug resistance, demonstrating a central role for EGFR and its downstream effector mTORC2, in cancer pathogenesis through metabolic reprogramming.

Awards and honors

Alpha Omega Alpha, Cornell University Medical College, 1991 Pfizer New Faculty Award (one in Neuroscience in United States), 1996 The Johnny Mercer Foundation Research Award, 2004 America’s Top Doctors for Cancer (Castle Connolly and ''U.S. News & World Report''), 2006–present Farber Award (top brain tumor research award given jointly by the American Association of Neurological Surgeons and the Society for NeuroOncology), 2007 American Society for Clinical Investigation, 2007 Profiled by Journal of ''Cell Biology'' in the “People and Ideas” section, 2008 President, American Society for Clinical Investigation, 2010–2011 Association of American Physicians, 2012 Elected Fellow, American Association for the Advancement of Science, 2015

Personal life

Mischel lives in

La Jolla La Jolla ( , ) is a hilly, seaside neighborhood within the city of San Diego, California, United States, occupying of curving coastline along the Pacific Ocean. The population reported in the 2010 census was 46,781. La Jolla is surrounded on ...

, California with his wife, Deborah Kado, a Professor of Medicine at

, and his daughters Anna and Sarah.

References

External links

Paul Mischell's lab website
{{DEFAULTSORT:Mischel, Paul 1962 births Living people University of Pennsylvania alumni Cancer researchers Fellows of the American Association for the Advancement of Science Weill Cornell Medical College alumni University of California, Los Angeles faculty University of California, San Diego faculty Members of the National Academy of Medicine