Paul Mischel

Paul Salomon Mischel
Born (1962-07-13) July 13, 1962
Syracuse, NY, USA.
Education
Known forExtrachromosomal DNA in cancer (ecDNA)
RelativesDoborah Kado, M.D. Walter Mischel
Scientific career
FieldsCancer genetics and pathology
WorkplacesStanford University, University of California, San Diego, University of California, Los Angeles
WebsiteGroup Website

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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][2]He is the Fortinet Founders Professor, Vice Chair for Research for the Department of Pathology, and Deputy Director of Translational Science and an Institute Scholar at Sarafan ChEM-H, Stanford University. Mischel leads Team eDyNAmiC of the Cancer Grand Challenges program, tackling the challenge of extrachromosomal DNA (ecDNA) in cancer development, progression, and therapeutic resistance. Their research is published in papers in Nature, Science, and Cell, and highlighted in a recent profile in Science Magazine[3], as well as being highlighted in the “Clinical Implications of Basic Research” section of the New England Journal of Medicine[4]. Their work was also recently highlighted in The Economist Magazine[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, 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 is also Deputy Director of Translational Science and an Institute Scholar at Sarafan ChEM-H, Stanford University. Mischel leads team eDyNAmiC of the Cancer Grand Challenges program.

Research

Genes are passed on chromosomes from parents to children and from mother cells to daughter cells when they divide, including in cancer. However, extensive tumor cell to tumor cell variability and rapid genome change of some cancers calls this assumption into question. Mischel set out to ask where genes are amplified in cancer. Resurrecting a discovery made over 60 years ago, but incompletely understood, he discovered the critical importance for extrachromosomal DNA (ecDNA) in cancer. Deploying the tools of modern molecular biology and cell biology, to decipher ecDNAs and how they function, he demonstrated that ecDNAs are circular, double stranded, chromatinized DNA, often of 1-5 milion base pairs enriched for oncogenes, immunomodulatory genes, and gene regulatory elements. With colleagues, including Howard Chang, he showed they can be transforming and demonstrated how their altered structure generates new forms of long-range gene regulation, rewiring epigenetic structure, and driving massive oncogene transcription. These discoveries have enhanced the fundamental understanding of the molecular basis of nearly 20% of all cancers, opening a new field, promising new treatments targeting genes and proteins involved in this unique biology, demonstrating the importance of non-Mendelian inheritance of oncogenes in cancer development and treatment resistance.[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]

Honors

Mischel is a member of the National Academy of Medicine[21], a Fellow of the AACR Academy, 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

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

  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. ↑ "Paul Mischel", Wikipedia, 2025-10-01, retrieved 2026-07-02
  3. ↑ "Weird rings of DNA fuel cancers. This scientist leads the effort to target them". www.science.org. Retrieved 2026-07-02.
  4. ↑ Siu, Lillian L.; Pugh, Trevor J. (2025-04-09). "Extrachromosomal DNA — Amping Up Cancer". New England Journal of Medicine. 392 (14): 1447–1450. doi:10.1056/NEJMcibr2415911. ISSN 0028-4793.
  5. ↑ "Tumour cells use a genetic trick to become drug-resistant". The Economist. ISSN 0013-0613. Retrieved 2026-07-02.
  6. ↑ 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. Bibcode:2014Sci...343...72N. doi:10.1126/science.1241328. ISSN 0036-8075. PMC 4049335. PMID 24310612.
  7. ↑ 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. Bibcode:2017Natur.543..122T. doi:10.1038/nature21356. ISSN 1476-4687. PMC 5334176. PMID 28178237.
  8. ↑ 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. Bibcode:2019Natur.575..699W. doi:10.1038/s41586-019-1763-5. ISSN 1476-4687. PMC 7094777. PMID 31748743.
  9. ↑ 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. PMID 39402156.
  10. ↑ 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. Bibcode:2021Natur.600..731H. doi:10.1038/s41586-021-04116-8. ISSN 1476-4687. PMC 9126690. PMID 34819668.
  11. ↑ 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. Bibcode:2022Natur.602..510B. doi:10.1038/s41586-022-04398-6. ISSN 1476-4687. PMC 8850194. PMID 35140399.
  12. ↑ 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. PMID 36123406.
  13. ↑ 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. PMC 9649439. PMID 36253572.
  14. ↑ 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. Bibcode:2023Natur.616..798L. doi:10.1038/s41586-023-05937-5. ISSN 1476-4687. PMC 10132967. PMID 37046089.
  15. ↑ 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. Bibcode:2024Natur.635..210T. doi:10.1038/s41586-024-07802-5. ISSN 1476-4687. PMC 11540844. PMID 39506153.
  16. ↑ 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. Bibcode:2024Natur.635..193B. doi:10.1038/s41586-024-08107-3. ISSN 1476-4687. PMC 11540846. PMID 39506150.
  17. ↑ 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. Bibcode:2024Natur.635..201H. doi:10.1038/s41586-024-07861-8. ISSN 1476-4687. PMC 11541006. PMID 39506152.
  18. ↑ Sankar, Venkat; Hung, King L.; Gnanasekar, Aditi; Wong, Ivy Tsz-Lo; Shi, Quanming; Kraft, Katerina; Jones, Matthew G.; He, Britney Jiayu; Yan, Xiaowei; Belk, Julia A.; Liu, Kevin J.; Agarwal, Sangya; Wang, Sean K.; Henssen, Anton G.; Mischel, Paul S. (January 2026). "Genetic elements promote retention of extrachromosomal DNA in cancer cells". Nature. 649 (8095): 152–160. doi:10.1038/s41586-025-09764-8. ISSN 1476-4687.
  19. ↑ Yi, Hyerim; Zhang, Shu; Swinderman, Jason; Wang, Yanbo; Kanakaveti, Vishnupriya; Hung, King L.; Wong, Ivy Tsz-Lo; Srinivasan, Suhas; Curtis, Ellis J.; Bhargava-Shah, Aarohi; Li, Rui; Jones, Matthew G.; Luebeck, Jens; Bailey, Chris; Zhao, Yanding (2026-02-05). "EcDNA-borne structural variants drive oncogenic fusion transcript amplification". Cell. 189 (3): 906–921.e20. doi:10.1016/j.cell.2025.12.009. ISSN 0092-8674. PMID 41506267.
  20. ↑ Wong, Ivy Tsz-Lo; Bailey, Chris; Wu, Sihan; Henssen, Anton G.; Cravatt, Benjamin F.; Chen, Zhijian J.; Bafna, Vineet; Jamal-Hanjani, Mariam; Swanton, Charlie; Chang, Howard Y.; Mischel, Paul S. (2026-04-16). "A recipe for chaos: Extrachromosomal DNA and the hallmarks of cancer". Cell. 189 (8): 2307–2321. doi:10.1016/j.cell.2026.03.011. ISSN 0092-8674. PMID 41997126.
  21. ↑ "Six professors elected to the National Academy of Medicine". News Center. 2021-10-20. Retrieved 2024-11-22.

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