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Paul Mischel

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Paul Salomon Mischel
Born (1962-07-13) July 13, 1962 (age 62)
Syracuse, NY, USA.
Education
Known forExtrachromosomal DNA in cancer (ecDNA)
RelativesDoborah Kado, M.D. Walter Mischel
AwardsNational Academy of Medicine

Ernst W. Bertner Prize for Distinbuished Contributions to Cancer Research

American Society for Clinical Investigation (President, 2010/2011)

American Association of Physicians

Fellow, American Association for the Advancement of Science
Scientific career
FieldsCancer genetics and pathology
InstitutionsStanford University, University of California, San Diego, University of California, Los Angeles
WebsiteGroup Website

PubMed

Stanford Profile

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Paul S. Mischel (born July 13, 1962) is a physician-scientist whose laboratory has made pioneering discoveries in the pathogenesis of human cancer.[1] He is the Fortinet Founders Professor, and Vice Chair for Research for the Department of Pathology, Stanford Medicine, an Institute Scholar in Sarafan ChEM-H. He is also a Faculty Advisor for Experimental Biology at the Innovative Medicines Accelerator at Stanford University. Mischel’s research published in a series of papers in Nature and Science, has catalyzed a paradigm shift in precision oncology that promises to transform the diagnosis and treatment of patients suffering from some of the most aggressive forms of cancer.[2]

Career

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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, graduating Alpha Omega Alpha. Mischel completed residency training in Anatomic Pathology and Neuropathology at UCLA, 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. 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. Mischel leads the team of eDyNAmiC project.

Research

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Mischel’s research has demonstrated a central role for ecDNA in cancer. Studies he has led, published in a series of papers in Nature and Science, has provided a mechanistic understanding of the molecular basis of intratumoral genetic heterogeneity, accelerated evolution and treatment resistance driven by ecDNA oncogene amplification. His team’s research has shown that ecDNA occurs in close to 20% of all solid cancers, of women and men, children and adults, that it is associated with poor outcome for patients. This research has revealed clinical implications and underlying molecular mechanisms of ecDNA in cancer development and progression, suggesting the potential for future ecDNA-directed cancer treatments.[3][4][5][6][7][8][9][10][11][12][13][14]

Honors

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Mischel is a member of the National Academy of Medicine[15] and recipient of the Ernst W. Bertner Memorial Award from MD Anderson for Distinguished Contributions to Cancer Research. Mischel is also an elected Fellow and Past-President of the American Society for Clinical Investigation, and an elected Fellow of the American Association of Physicians and The American Association for the Advancement of Science.

Personal life

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Mischel is married to Professor Deborah Kado, Chief of Geriatrics Research, co-director of the Stanford Longevity Center, and Director of the Palo Alto VA Geriatrics Research, Education, and Clinical Center. They have two daughters, Dr. Anna Mischel and Dr. Sarah Mischel.  Paul is the son of the cognitive philosopher Theodore Mischel and the nephew of the famed psychologist, Walter Mischel.

References

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  1. ^ Gunn, Tim (2023-02-20). "The ecDNA story – catching the mastermind behind cancer evolution". Cancer Research UK - Cancer News. Retrieved 2024-11-22.
  2. ^ "Shining a light on extrachromosomal DNA | Sarafan ChEM-H". chemh.stanford.edu. 2021-09-29. Retrieved 2024-11-22.
  3. ^ Nathanson, David A.; Gini, Beatrice; Mottahedeh, Jack; Visnyei, Koppany; Koga, Tomoyuki; Gomez, German; Eskin, Ascia; Hwang, Kiwook; Wang, Jun; Masui, Kenta; Paucar, Andres; Yang, Huijun; Ohashi, Minori; Zhu, Shaojun; Wykosky, Jill (2014-01-03). "Targeted Therapy Resistance Mediated by Dynamic Regulation of Extrachromosomal Mutant EGFR DNA". Science. 343 (6166): 72–76. doi:10.1126/science.1241328. ISSN 0036-8075. PMC 4049335. PMID 24310612.
  4. ^ Turner, Kristen M.; Deshpande, Viraj; Beyter, Doruk; Koga, Tomoyuki; Rusert, Jessica; Lee, Catherine; Li, Bin; Arden, Karen; Ren, Bing; Nathanson, David A.; Kornblum, Harley I.; Taylor, Michael D.; Kaushal, Sharmeela; Cavenee, Webster K.; Wechsler-Reya, Robert (March 2017). "Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity". Nature. 543 (7643): 122–125. doi:10.1038/nature21356. ISSN 1476-4687. PMC 5334176.
  5. ^ Wu, Sihan; Turner, Kristen M.; Nguyen, Nam; Raviram, Ramya; Erb, Marcella; Santini, Jennifer; Luebeck, Jens; Rajkumar, Utkrisht; Diao, Yarui; Li, Bin; Zhang, Wenjing; Jameson, Nathan; Corces, M. Ryan; Granja, Jeffrey M.; Chen, Xingqi (November 2019). "Circular ecDNA promotes accessible chromatin and high oncogene expression". Nature. 575 (7784): 699–703. doi:10.1038/s41586-019-1763-5. ISSN 1476-4687. PMC 7094777.
  6. ^ Kim, Hoon; Kim, Soyeon; Wade, Taylor; Yeo, Eunchae; Lipsa, Anuja; Golebiewska, Anna; Johnson, Kevin C.; An, Sepil; Ko, Junyong; Nam, Yoonjoo; Lee, Hwa Yeon; Kang, Seunghyun; Chung, Heesuk; Niclou, Simone P.; Moon, Hyo-Eun (November 2024). "Mapping extrachromosomal DNA amplifications during cancer progression". Nature Genetics. 56 (11): 2447–2454. doi:10.1038/s41588-024-01949-7. ISSN 1546-1718. PMC 11549044.
  7. ^ Hung, King L.; Yost, Kathryn E.; Xie, Liangqi; Shi, Quanming; Helmsauer, Konstantin; Luebeck, Jens; Schöpflin, Robert; Lange, Joshua T.; Chamorro González, Rocío; Weiser, Natasha E.; Chen, Celine; Valieva, Maria E.; Wong, Ivy Tsz-Lo; Wu, Sihan; Dehkordi, Siavash R. (December 2021). "ecDNA hubs drive cooperative intermolecular oncogene expression". Nature. 600 (7890): 731–736. doi:10.1038/s41586-021-04116-8. ISSN 1476-4687. PMC 9126690.
  8. ^ Bergstrom, Erik N.; Luebeck, Jens; Petljak, Mia; Khandekar, Azhar; Barnes, Mark; Zhang, Tongwu; Steele, Christopher D.; Pillay, Nischalan; Landi, Maria Teresa; Bafna, Vineet; Mischel, Paul S.; Harris, Reuben S.; Alexandrov, Ludmil B. (February 2022). "Mapping clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA". Nature. 602 (7897): 510–517. doi:10.1038/s41586-022-04398-6. ISSN 1476-4687. PMC 8850194.
  9. ^ Lange, Joshua T.; Rose, John C.; Chen, Celine Y.; Pichugin, Yuriy; Xie, Liangqi; Tang, Jun; Hung, King L.; Yost, Kathryn E.; Shi, Quanming; Erb, Marcella L.; Rajkumar, Utkrisht; Wu, Sihan; Taschner-Mandl, Sabine; Bernkopf, Marie; Swanton, Charles (October 2022). "The evolutionary dynamics of extrachromosomal DNA in human cancers". Nature Genetics. 54 (10): 1527–1533. doi:10.1038/s41588-022-01177-x. ISSN 1546-1718. PMC 9534767.
  10. ^ Hung, King L.; Luebeck, Jens; Dehkordi, Siavash R.; Colón, Caterina I.; Li, Rui; Wong, Ivy Tsz-Lo; Coruh, Ceyda; Dharanipragada, Prashanthi; Lomeli, Shirley H.; Weiser, Natasha E.; Moriceau, Gatien; Zhang, Xiao; Bailey, Chris; Houlahan, Kathleen E.; Yang, Wenting (November 2022). "Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH". Nature Genetics. 54 (11): 1746–1754. doi:10.1038/s41588-022-01190-0. ISSN 1546-1718.
  11. ^ Luebeck, Jens; Ng, Alvin Wei Tian; Galipeau, Patricia C.; Li, Xiaohong; Sanchez, Carissa A.; Katz-Summercorn, Annalise C.; Kim, Hoon; Jammula, Sriganesh; He, Yudou; Lippman, Scott M.; Verhaak, Roel G. W.; Maley, Carlo C.; Alexandrov, Ludmil B.; Reid, Brian J.; Fitzgerald, Rebecca C. (April 2023). "Extrachromosomal DNA in the cancerous transformation of Barrett's oesophagus". Nature. 616 (7958): 798–805. doi:10.1038/s41586-023-05937-5. ISSN 1476-4687. PMC 10132967.
  12. ^ Tang, Jun; Weiser, Natasha E.; Wang, Guiping; Chowdhry, Sudhir; Curtis, Ellis J.; Zhao, Yanding; Wong, Ivy Tsz-Lo; Marinov, Georgi K.; Li, Rui; Hanoian, Philip; Tse, Edison; Mojica, Salvador Garcia; Hansen, Ryan; Plum, Joshua; Steffy, Auzon (November 2024). "Enhancing transcription–replication conflict targets ecDNA-positive cancers". Nature. 635 (8037): 210–218. doi:10.1038/s41586-024-07802-5. ISSN 1476-4687. PMC 11540844.
  13. ^ Bailey, Chris; Pich, Oriol; Thol, Kerstin; Watkins, Thomas B. K.; Luebeck, Jens; Rowan, Andrew; Stavrou, Georgia; Weiser, Natasha E.; Dameracharla, Bhargavi; Bentham, Robert; Lu, Wei-Ting; Kittel, Jeanette; Yang, S. Y. Cindy; Howitt, Brooke E.; Sharma, Natasha (November 2024). "Origins and impact of extrachromosomal DNA". Nature. 635 (8037): 193–200. doi:10.1038/s41586-024-08107-3. ISSN 1476-4687. PMC 11540846.
  14. ^ Hung, King L.; Jones, Matthew G.; Wong, Ivy Tsz-Lo; Curtis, Ellis J.; Lange, Joshua T.; He, Britney Jiayu; Luebeck, Jens; Schmargon, Rachel; Scanu, Elisa; Brückner, Lotte; Yan, Xiaowei; Li, Rui; Gnanasekar, Aditi; Chamorro González, Rocío; Belk, Julia A. (November 2024). "Coordinated inheritance of extrachromosomal DNAs in cancer cells". Nature. 635 (8037): 201–209. doi:10.1038/s41586-024-07861-8. ISSN 1476-4687. PMC 11541006.
  15. ^ "Six professors elected to the National Academy of Medicine". News Center. 2021-10-20. Retrieved 2024-11-22.
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Team eDyNAmiC: Following the science and accelerating our understanding of ecDNA

Cracking the code of DNA circles in cancer, Stanford Medicine-led team uncovers potential therapy

Study raises hopes of treating aggressive cancers by zapping rogue DNA

The cartographer of cancer

Coming full circle with extrachromosomal DNA, cancer and Ptolemy

Cancers cheat during mitosis to pass on their most malignant genes

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