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词条 Paul Mischel
释义

  1. Career

  2. Research

      Extrachromosomal oncogene amplification    Metabolic co-dependency pathways in cancer  

  3. Awards and honors

  4. Personal life

  5. References

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 Distinguished Professor at the University of California San Diego.,[1] and a member of the Ludwig Institute for Cancer Research.[2] Mischel was elected into the American Society for Clinical Investigation (ASCI),[3] serving as ASCI president in 2010/11. He was inducted into the American Association of Physicians, and was elected as a fellow of the American Association for the Advancement of Science[4][5]

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 and received his M.D. from Cornell University Medical College in 1991,[6] graduating Alpha Omega Alpha. Mischel completed residency training in Anatomic Pathology and Neuropathology at UCLA,[7] followed by post-doctoral research training with Louis Reichardt at HHMI-UCSF. Mischel joined the faculty of UCLA in 1998. In August 2012, he was recruited to the Ludwig Institute for Cancer Research, San Diego and UCSD.

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),[8] 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.[9][10][11][12] 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.[13][14][15]

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.[16][17][18][19][20] These studies, focused primarily on the highly lethal brain cancer, glioblastoma, 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.[21][22][23]

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 US News and World Report), 2006–present[6]

Farber Award (top brain tumor research award given jointly by the American Association of Neurological Surgeons and the Society for NeuroOncology), 2007[24]

American Society for Clinical Investigation, 2007[3]

Profiled by Journal of Cell Biology in the “People and Ideas” section, 2008[25]

President, American Society for Clinical Investigation, 2011

American Association of Physicians, 2012

Elected Fellow, American Association for the Advancement of Science, 2015[4][5]

Personal life

Mischel lives in La Jolla, California with his wife, Deborah Kado, a Professor of Medicine at UCSD, and his daughters Anna and Sarah.

References

1. ^{{Cite web|url=https://profiles.ucsd.edu/paul.mischel|title=Paul Mischel {{!}} UCSD Profiles|website=profiles.ucsd.edu|access-date=2019-01-29}}
2. ^{{Cite web|url=https://www.ludwigcancerresearch.org/location/san-diego-branch/paul-s-mischel-lab|title=Paul S. Mischel lab {{!}} Ludwig Institute for Cancer Research|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}
3. ^1 {{Cite web|url=https://www.the-asci.org/controllers/asci/AsciProfileController.php?pid=500580|title=The American Society for Clinical Investigation|language=en-US|access-date=2019-01-31}}
4. ^1 {{Cite web|url=http://www.eurekalert.org/pub_releases/2015-11/lifc-lsd112015.php|title=Ludwig San Diego's Paul Mischel elected AAAS Fellow|website=EurekAlert!|access-date=2019-01-29}}
5. ^1 {{Cite web|url=https://www.aaas.org/news/2015-aaas-fellows-recognized-contributions-advancing-science|title=2015 AAAS Fellows Recognized for Contributions to Advancing Science|website=American Association for the Advancement of Science|access-date=2019-01-29}}
6. ^1 {{Cite web|url=https://health.usnews.com/doctors/paul-mischel-7916|title=Dr. Paul Mischel, Pathologist in La Jolla, CA {{!}} US News Doctors|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}
7. ^{{Cite web|url=https://people.healthsciences.ucla.edu/institution/personnel?personnel_id=8894|title=Faculty Database Production Server {{!}} David Geffen School of Medicine at UCLA|website=people.healthsciences.ucla.edu|access-date=2019-01-30}}
8. ^{{Cite web|url=https://cgap.nci.nih.gov/Chromosomes/Mitelman|title=Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer|website=cgap.nci.nih.gov|access-date=2018-11-27}}
9. ^{{Cite journal|last=Nathanson|first=David A.|last2=Gini|first2=Beatrice|last3=Mottahedeh|first3=Jack|last4=Visnyei|first4=Koppany|last5=Koga|first5=Tomoyuki|last6=Gomez|first6=German|last7=Eskin|first7=Ascia|last8=Hwang|first8=Kiwook|last9=Mischel|first9=Paul S.|date=2014-01-03|title=Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA|journal=Science|volume=343|issue=6166|pages=72–76|doi=10.1126/science.1241328|issn=0036-8075|pmid=24310612|pmc=4049335}}
10. ^{{Cite journal|last=Turner|first=Kristen M.|last2=Deshpande|first2=Viraj|last3=Beyter|first3=Doruk|last4=Koga|first4=Tomoyuki|last5=Rusert|first5=Jessica|last6=Lee|first6=Catherine|last7=Li|first7=Bin|last8=Arden|first8=Karen|last9=Mischel|first9=Paul S.|date=2017-02-08|title=Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity|journal=Nature|volume=543|issue=7643|pages=122–125|doi=10.1038/nature21356|pmid=28178237|pmc=5334176|issn=0028-0836}}
11. ^{{Cite web|url=https://www.sandiegouniontribune.com/business/biotech/sd-me-cancer-genes-20170208-story.html|title=Cancer genes hide outside chromosomes|last=Fikes|first=Bradley J.|website=sandiegouniontribune.com|language=en-US|access-date=2019-01-31}}
12. ^{{Cite web|url=https://www.the-scientist.com/daily-news/non-chromosomal-dna-drives-tumor-evolution-32051|title=Non-Chromosomal DNA Drives Tumor Evolution|website=The Scientist Magazine®|language=en|access-date=2019-02-01}}
13. ^{{Cite journal|last=Furnari|first=Frank B.|last2=Cloughesy|first2=Timothy F.|last3=Cavenee|first3=Webster K.|last4=Mischel|first4=Paul S.|date=2015-04-09|title=Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma|journal=Nature Reviews Cancer|volume=15|issue=5|pages=302–310|doi=10.1038/nrc3918|pmid=25855404|pmc=4875778|issn=1474-175X}}
14. ^{{Cite journal|last=Pennisi|first=Elizabeth|date=2017-06-09|title=Circular DNA throws biologists for a loop|journal=Science|language=en|volume=356|issue=6342|pages=996|doi=10.1126/science.356.6342.996|issn=0036-8075|pmid=28596318}}
15. ^{{Cite journal|last=Aranda|first=Victoria|date=2014-01-07|title=Cancer: Extrachromosomal resistance|journal=Nature Medicine|language=en|volume=20|pages=28|doi=10.1038/nm.3452|issn=1546-170X}}
16. ^{{Cite journal|last=Masui|first=Kenta|last2=Tanaka|first2=Kazuhiro|last3=Akhavan|first3=David|last4=Babic|first4=Ivan|last5=Gini|first5=Beatrice|last6=Matsutani|first6=Tomoo|last7=Iwanami|first7=Akio|last8=Liu|first8=Feng|last9=Mischel|first9=Paul S.|date=2013-11-05|title=mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc|journal=Cell Metabolism|volume=18|issue=5|pages=726–739|doi=10.1016/j.cmet.2013.09.013|issn=1932-7420|pmc=3840163|pmid=24140020}}
17. ^{{Cite journal|last=Masui|first=Kenta|last2=Tanaka|first2=Kazuhiro|last3=Ikegami|first3=Shiro|last4=Villa|first4=Genaro R.|last5=Yang|first5=Huijun|last6=Yong|first6=William H.|last7=Cloughesy|first7=Timothy F.|last8=Yamagata|first8=Kanato|last9=Mischel|first9=Paul S.|date=2015-07-28|title=Glucose-dependent acetylation of Rictor promotes targeted cancer therapy resistance|journal=Proceedings of the National Academy of Sciences|volume=112|issue=30|pages=9406–9411|doi=10.1073/pnas.1511759112|issn=0027-8424|pmid=26170313|pmc=4522814}}
18. ^{{Cite journal|last=Babic|first=Ivan|last2=Anderson|first2=Erik S.|last3=Tanaka|first3=Kazuhiro|last4=Guo|first4=Deliang|last5=Masui|first5=Kenta|last6=Li|first6=Bing|last7=Zhu|first7=Shaojun|last8=Gu|first8=Yuchao|last9=Mishcel|first9=Paul S.|date=2013-06-04|title=EGFR mutation-induced alternative splicing of Max contributes to growth of glycolytic tumors in brain cancer|journal=Cell Metabolism|volume=17|issue=6|pages=1000–1008|doi=10.1016/j.cmet.2013.04.013|issn=1932-7420|pmc=3679227|pmid=23707073}}
19. ^{{Cite journal|last=Gu|first=Yuchao|last2=Albuquerque|first2=Claudio P.|last3=Braas|first3=Daniel|last4=Zhang|first4=Wei|last5=Villa|first5=Genaro R.|last6=Bi|first6=Junfeng|last7=Ikegami|first7=Shiro|last8=Masui|first8=Kenta|last9=Mischel|first9=Paul S.|date=2017-07-06|title=mTORC2 Regulates Amino Acid Metabolism in Cancer by Phosphorylation of the Cystine-Glutamate Antiporter xCT|journal=Molecular Cell|volume=67|issue=1|pages=128–138.e7|doi=10.1016/j.molcel.2017.05.030|issn=1097-4164|pmc=5521991|pmid=28648777}}
20. ^{{Cite journal|last=Guo|first=Deliang|last2=Reinitz|first2=Felicia|last3=Youssef|first3=Mary|last4=Hong|first4=Cynthia|last5=Nathanson|first5=David|last6=Akhavan|first6=David|last7=Kuga|first7=Daisuke|last8=Amzajerdi|first8=Ali Nael|last9=Mischel|first9=Paul S.|date=2011-10-01|title=An LXR Agonist Promotes Glioblastoma Cell Death through Inhibition of an EGFR/AKT/SREBP-1/LDLR–Dependent Pathway|url=http://cancerdiscovery.aacrjournals.org/content/1/5/442|journal=Cancer Discovery|volume=1|issue=5|pages=442–456|doi=10.1158/2159-8290.CD-11-0102|issn=2159-8274|pmid=22059152|pmc=3207317|via=}}
21. ^{{Cite journal|last=Masui|first=Kenta|last2=Cavenee|first2=Webster K.|last3=Mischel|first3=Paul S.|date=2014-07-25|title=mTORC2 in the center of cancer metabolic reprogramming|journal=Trends in Endocrinology and Metabolism|volume=25|issue=7|pages=364–373|doi=10.1016/j.tem.2014.04.002|issn=1879-3061|pmc=4077930|pmid=24856037}}
22. ^{{Cite journal|last=Wu|first=Si-Han|last2=Bi|first2=Jun-Feng|last3=Cloughesy|first3=Timothy|last4=Cavenee|first4=Webster K.|last5=Mischel|first5=Paul S.|date=2014|title=Emerging function of mTORC2 as a core regulator in glioblastoma: metabolic reprogramming and drug resistance|journal=Cancer Biology & Medicine|volume=11|issue=4|pages=255–263|doi=10.7497/j.issn.2095-3941.2014.04.004|issn=2095-3941|pmc=4296088|pmid=25610711}}
23. ^{{Cite journal|last=Bi|first=Junfeng|last2=Wu|first2=Sihan|last3=Zhang|first3=Wenjing|last4=Mischel|first4=Paul S.|date=2018-05-23|title=Targeting cancer's metabolic co-dependencies: A landscape shaped by genotype and tissue context|journal=Biochimica et Biophysica Acta (BBA) - Reviews on Cancer|volume=1870|issue=1|pages=76–87|doi=10.1016/j.bbcan.2018.05.002|issn=1879-2561|pmc=6193564|pmid=29775654}}
24. ^{{Cite web|url=https://www.soc-neuro-onc.org/SNO/About_SNO/SNO_Awards/SNO/About_SNO/SNO_Awards.aspx?hkey=398d4b7f-2afd-41c5-9cd9-0a6a410abb2f|title=SNO Awards|website=www.soc-neuro-onc.org|access-date=2019-01-31}}
25. ^{{Cite journal|last=Williams|first=Ruth|date=2008-06-30|title=Paul Mischel: All about brains|journal=The Journal of Cell Biology|language=en|volume=181|issue=7|pages=1044–1045|doi=10.1083/jcb.1817pi|issn=0021-9525|pmid=18591424|pmc=2442209}}
{{authority control}}{{DEFAULTSORT:Mischel, Paul}}

8 : 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
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