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Craig B. Thompson

Not to be confused with Craig Thomson.
Craig B. Thompson
Born1953 (age 70–71)
Alma mater
SpouseTullia Lindsten[1]
Scientific career
Institutions
WebsiteThe Craig Thompson Lab

Craig B. Thompson (born 1953) is an American cell biologist and a former president of the Memorial Sloan Kettering Cancer Center.[1]

Education and career

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Thompson received his bachelor's degree from Dartmouth College and went on to earn his medical degree in 1977 from the University of Pennsylvania Medical School. He received clinical training in internal medicine at Harvard Medical School and in medical oncology at the Fred Hutchinson Cancer Research Center at the University of Washington. After completing his training, Thompson became a physician at the National Naval Medical Center in Bethesda, Maryland, and an assistant professor of medicine at the Uniformed Services University of the Health Sciences. In 1987, he joined the faculty of the University of Michigan as an assistant professor of medicine and an assistant investigator in the Howard Hughes Medical Institute. From 1993 until he joined the University of Pennsylvania, he was affiliated with the University of Chicago, where he was professor of medicine, a Howard Hughes investigator, and director of the Gwen Knapp Center for Lupus and Immunology Research.

Thompson joined the University of Pennsylvania in 1999 as a professor of medicine, the scientific director of The Leonard and Madlyn Abramson Family Cancer Research Institute, and the first chairman of the Department of Cancer Biology. In 2006 he was named director of the Abramson Cancer Center of the University of Pennsylvania and associate vice president for cancer services of the University of Pennsylvania Health System.

Thompson became president and chief executive officer of Memorial Sloan Kettering Cancer Center in November 2010.

He is married to Tullia Lindsten, also a cancer researcher.[1]

Research

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Thompson's laboratory undertakes basic research in the fields of cancer biology and immunology. This research has helped advance the understanding and deployment of immunotherapy to treat cancer. Thompson has studied how genes regulate apoptosis and metabolism, and investigated their application in treating cancer.[2]

In his earlier work, Thompson was among the first to describe the unique co-stimulatory properties of CD28 in augmenting lymphoid effector function, proliferation, and survival. Thompson identified the evolutionary duplication of CD28 into CD28 and CTLA-4 and demonstrated that CTLA4 had an inhibitory effect on immune activation.[3][4][5][6]

Thompson elucidated processes on the genes that control programmed cell death or apoptosis.[7] These processes shape lymphocyte development and immune system homeostasis. His group discovered the first Bcl-2 homolog to be identified, Bcl-Xl, and described the first BH3-only containing regulatory family member, Bcl-xS.[8] He published this work alongside Stanley Korsmeyer's report of the first pro-apoptotic family member, Bax, and together established the three classes of this gene family and defined their pro-apoptotic and anti-apoptotic roles.[9][10][11]

Thompson's recent research has focused on cellular metabolism. His discoveries in growth factor regulation of nutrient uptake and metabolism have provided direct mechanistic links between cellular metabolism and cell growth and survival.[12][13][14][15] His work has also led to new insights into how intracellular metabolite levels can contribute to the regulation of gene expression, cellular differentiation and oncogenic transformation. This work has contributed to the resurgent interest in cancer cell metabolism and may form the basis for translational therapies to exploit the metabolic addictions exhibited by cancer cells.[16][17][18][19]

Scientific contributions and patents

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Thompson holds more than 30 patents related to immunotherapy and apoptosis, and is a founder of three biotechnology companies.[2]

Patents arising from Thompson's research describing the co-stimulatory/inhibitory properties of CD28/CTLA-4, in collaboration with Carl June and Jeffrey Bluestone, were licensed for the development of Abatacept (Orencia) for autoimmune diseases and for use in T cell cloning and CAR T cell production.[20][21][22]

Thompson's work with Stanley Korsmeyer establishing the existence of three classes of Bcl-2-related proteins and defining their role in apoptosis led to the development of ABT-263 (navitoclax) and ABT-199 (venetoclax), recently FDA-approved for certain patients with chronic lymphocytic leukemia (CLL).[citation needed]

Thompson's discovery of oncogenic metabolites (succinate, fumarate, and 2-hydroxyglutarate) that can inhibit tumor suppressor function and/or impair cellular differentiation has helped lead to the development of new treatments for leukemia, gliomas, sarcomas, and bladder cancer, currently in clinical trials.[23]

Criticism

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In December 2011, The University and its Abramson Family Cancer Research Institute sued Thompson after his move to Memorial Sloan Kettering, charging that he had made use of research conducted at the University of Pennsylvania to start a biotechnology company, Agios Pharmaceuticals that Thompson had co-founded in 2007 while still at the University.[24]

While most of the details were not announced, the suit was settled with an agreement wherein Agios entered into a licensing agreement with the University of Pennsylvania regarding specific intellectual property.[25][26]

Other roles

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Past roles

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Awards and honors

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References

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  1. ^ a b c "Craig Thompson Named President of Memorial Sloan-Kettering". mskcc.org. 1 October 2010. Retrieved 6 September 2012.
  2. ^ a b "Leadership | Board or Directors, Founders, Scientific Advisors | Agios". www.agios.com. Retrieved 26 July 2017.
  3. ^ June, CH; Ledbetter, JA; Gillespie, MM; Lindsten, T; Thompson, CB (December 1987). "T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression". Molecular and Cellular Biology. 7 (12): 4472–81. doi:10.1128/MCB.7.12.4472. PMC 368131. PMID 2830495.
  4. ^ Thompson, CB; Lindsten, T; Ledbetter, JA; Kunkel, SL; Young, HA; Emerson, SG; Leiden, JM; June, CH (February 1989). "CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines". Proceedings of the National Academy of Sciences of the United States of America. 86 (4): 1333–7. Bibcode:1989PNAS...86.1333T. doi:10.1073/pnas.86.4.1333. PMC 286684. PMID 2465550.
  5. ^ Walunas, TL; Lenschow, DJ; Bakker, CY; Linsley, PS; Freeman, GJ; Green, JM; Thompson, CB; Bluestone, JA (August 1994). "CTLA-4 can function as a negative regulator of T cell activation". Immunity. 1 (5): 405–13. doi:10.1016/1074-7613(94)90071-X. PMID 7882171.
  6. ^ Boise, LH; Minn, AJ; Noel, PJ; June, CH; Accavitti, MA; Lindsten, T; Thompson, CB (July 1995). "CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL". Immunity. 3 (1): 87–98. doi:10.1016/1074-7613(95)90161-2. PMID 7621080.
  7. ^ Boise, LH; González-García, M; Postema, CE; Ding, L; Lindsten, T; Turka, LA; Mao, X; Nuñez, G; Thompson, CB (27 August 1993). "bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death" (PDF). Cell. 74 (4): 597–608. doi:10.1016/0092-8674(93)90508-N. hdl:2027.42/30629. PMID 8358789. S2CID 13542617.
  8. ^ Sattler, M; Liang, H; Nettesheim, D; Meadows, RP; Harlan, JE; Eberstadt, M; Yoon, HS; Shuker, SB; Chang, BS; Minn, AJ; Thompson, CB; Fesik, SW (14 February 1997). "Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis". Science. 275 (5302): 983–6. doi:10.1126/science.275.5302.983. PMID 9020082. S2CID 22667419.
  9. ^ "National Academy of Science". nas.nasonline.org.
  10. ^ Lindsten, T; Ross, AJ; King, A; Zong, WX; Rathmell, JC; Shiels, HA; Ulrich, E; Waymire, KG; Mahar, P; Frauwirth, K; Chen, Y; Wei, M; Eng, VM; Adelman, DM; Simon, MC; Ma, A; Golden, JA; Evan, G; Korsmeyer, SJ; MacGregor, GR; Thompson, CB (December 2000). "The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues". Molecular Cell. 6 (6): 1389–99. doi:10.1016/S1097-2765(00)00136-2. PMC 3057227. PMID 11163212.
  11. ^ Wei, MC; Zong, WX; Cheng, EH; Lindsten, T; Panoutsakopoulou, V; Ross, AJ; Roth, KA; MacGregor, GR; Thompson, CB; Korsmeyer, SJ (27 April 2001). "Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death". Science. 292 (5517): 727–30. Bibcode:2001Sci...292..727W. doi:10.1126/science.1059108. PMC 3049805. PMID 11326099.
  12. ^ Rathmell, JC; Vander Heiden, MG; Harris, MH; Frauwirth, KA; Thompson, CB (September 2000). "In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability". Molecular Cell. 6 (3): 683–92. doi:10.1016/S1097-2765(00)00066-6. PMID 11030347.
  13. ^ Vander Heiden, MG; Plas, DR; Rathmell, JC; Fox, CJ; Harris, MH; Thompson, CB (September 2001). "Growth factors can influence cell growth and survival through effects on glucose metabolism". Molecular and Cellular Biology. 21 (17): 5899–912. doi:10.1128/MCB.21.17.5899-5912.2001. PMC 87309. PMID 11486029.
  14. ^ Lum, JJ; Bauer, DE; Kong, M; Harris, MH; Li, C; Lindsten, T; Thompson, CB (28 January 2005). "Growth factor regulation of autophagy and cell survival in the absence of apoptosis". Cell. 120 (2): 237–48. doi:10.1016/j.cell.2004.11.046. PMID 15680329.
  15. ^ Wise, DR; DeBerardinis, RJ; Mancuso, A; Sayed, N; Zhang, XY; Pfeiffer, HK; Nissim, I; Daikhin, E; Yudkoff, M; McMahon, SB; Thompson, CB (2 December 2008). "Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction". Proceedings of the National Academy of Sciences of the United States of America. 105 (48): 18782–7. Bibcode:2008PNAS..10518782W. doi:10.1073/pnas.0810199105. PMC 2596212. PMID 19033189.
  16. ^ Selak, MA; Armour, SM; MacKenzie, ED; Boulahbel, H; Watson, DG; Mansfield, KD; Pan, Y; Simon, MC; Thompson, CB; Gottlieb, E (January 2005). "Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase". Cancer Cell. 7 (1): 77–85. doi:10.1016/j.ccr.2004.11.022. PMID 15652751.
  17. ^ Ward, PS; Patel, J; Wise, DR; Abdel-Wahab, O; Bennett, BD; Coller, HA; Cross, JR; Fantin, VR; Hedvat, CV; Perl, AE; Rabinowitz, JD; Carroll, M; Su, SM; Sharp, KA; Levine, RL; Thompson, CB (16 March 2010). "The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate". Cancer Cell. 17 (3): 225–34. doi:10.1016/j.ccr.2010.01.020. PMC 2849316. PMID 20171147.
  18. ^ Figueroa, ME; Abdel-Wahab, O; Lu, C; Ward, PS; Patel, J; Shih, A; Li, Y; Bhagwat, N; Vasanthakumar, A; Fernandez, HF; Tallman, MS; Sun, Z; Wolniak, K; Peeters, JK; Liu, W; Choe, SE; Fantin, VR; Paietta, E; Löwenberg, B; Licht, JD; Godley, LA; Delwel, R; Valk, PJ; Thompson, CB; Levine, RL; Melnick, A (14 December 2010). "Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation". Cancer Cell. 18 (6): 553–67. doi:10.1016/j.ccr.2010.11.015. PMC 4105845. PMID 21130701.
  19. ^ Lu, C; Ward, PS; Kapoor, GS; Rohle, D; Turcan, S; Abdel-Wahab, O; Edwards, CR; Khanin, R; Figueroa, ME; Melnick, A; Wellen, KE; O'Rourke, DM; Berger, SL; Chan, TA; Levine, RL; Mellinghoff, IK; Thompson, CB (15 February 2012). "IDH mutation impairs histone demethylation and results in a block to cell differentiation". Nature. 483 (7390): 474–8. Bibcode:2012Natur.483..474L. doi:10.1038/nature10860. PMC 3478770. PMID 22343901.
  20. ^ Thompson, Craig B.; June, Carl H. (2004). "Methods of treating autoimmune disease via CTLA-4Ig". Retrieved 27 July 2017.
  21. ^ June, Carl H.; Thompson, Craig B.; Nabel, Gary J.; Gray, Gary S.; Rennert, Paul D.; Freeman, Gordon J. (1999). "Methods for selectively stimulating proliferation of T cells". Retrieved 27 July 2017.
  22. ^ Davis, Ryan. "Bristol-Myers Shells Out $21M To Settle Orencia Suit - Law360". www.law360.com. Retrieved 27 July 2017.
  23. ^ Apple, Sam (12 May 2016). "An Old Idea, Revived: Starve Cancer to Death". The New York Times. Retrieved 26 July 2017.
  24. ^ "Pollack, Andrew (5 February 2012). "Sloan-Kettering Chief Is Accused of Taking Research". The New York Times. Retrieved 6 September 2012.
  25. ^ Pollack, Andrew (31 August 2012). "Suits That Accused Sloan-Kettering Chief of Stealing Research Are Settled". nytimes.com. Retrieved 6 September 2012.
  26. ^ Mytelka, Andrew (1 September 2012). "Penn and Cancer Institute Settle Lawsuits Accusing Scientist of Stealing Research". The Chronicle of Higher Education. Retrieved 6 September 2012.
  27. ^ "Medical Advisory Board". HHMI.org. Retrieved 17 May 2017.
  28. ^ Foundation, Lasker. "2016 Lasker Awards | The Lasker Foundation". The Lasker Foundation. Retrieved 17 May 2017.
  29. ^ "Editorial Board: Cell". www.cell.com. Retrieved 17 May 2017.
  30. ^ "Masthead: Immunity". www.cell.com. Retrieved 17 May 2017.
  31. ^ "Editorial Board: Cancer Cell". www.cell.com. Retrieved 17 May 2017.
  32. ^ "Editors | Cancer Discovery". cancerdiscovery.aacrjournals.org. Retrieved 17 May 2017.
  33. ^ a b "Craig B. Thompson, MD". AACR.org. Retrieved 26 May 2017.
  34. ^ "09/19/06, Abramson Cancer Center Director: Craig Thompson - Almanac, Vol. 53, No. 4". www.upenn.edu. Retrieved 26 May 2017.
  35. ^ "Medical Advisory Board". HHMI.org. Retrieved 26 May 2017.
  36. ^ "Symposia on Cancer Research 2017" (PDF). mdanderson.org. Retrieved 26 May 2017.
  37. ^ "Symposium to Address Treatment and Prevention of Infectious Inflammatory and Oncogenic Disease - College of Medicine". College of Medicine. 5 June 2014. Retrieved 26 May 2017.
  38. ^ "ACP National Award Recipients" (PDF). American College Of Physicians. Archived from the original (PDF) on 5 August 2017. Retrieved 13 June 2017.
  39. ^ "Steven C. Beering Award | Office of Faculty Affairs and Professional Development". faculty.medicine.iu.edu. Archived from the original on 11 July 2018. Retrieved 26 May 2017.
  40. ^ "Award & PhD Recipients | Memorial Sloan Kettering Cancer Center". www.mskcc.org. Retrieved 26 May 2017.
  41. ^ "Craig Thompson". www.nasonline.org. Retrieved 26 May 2017.
  42. ^ "Recipients of Research Awards" (PDF). med.upenn.edu. Retrieved 26 May 2017.
  43. ^ a b "The American Society for Clinical Investigation". www.the-asci.org. Retrieved 26 May 2017.
  44. ^ "Craig B. Thompson, M.D." nam.edu. Retrieved 26 May 2017.
  45. ^ "Academy Member Connection". www.amacad.org. Archived from the original on 3 March 2018. Retrieved 26 May 2017.
  46. ^ "Association of American Physicians". aap-online.org. Retrieved 13 June 2017.
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