Craig B. Thompson Explained

Workplaces:
Alma Mater:
Spouse:Tullia Lindsten

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

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.

Research

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.

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.[2] [3] [4] [5]

Thompson elucidated processes on the genes that control programmed cell death or apoptosis.[6] 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.[7] 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.[8] [9] [10]

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.[11] [12] [13] [14] 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.[15] [16] [17] [18]

Scientific contributions and patents

Thompson holds more than 30 patents related to immunotherapy and apoptosis, and is a founder of three biotechnology companies.[19]

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).

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

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

Past roles

Awards and honors

External links

Notes and References

  1. News: Craig Thompson Named President of Memorial Sloan-Kettering. 1 October 2010. mskcc.org. 6 September 2012.
  2. June. CH. Ledbetter. JA. Gillespie. MM. Lindsten. T. Thompson. CB. T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression.. Molecular and Cellular Biology. December 1987. 7. 12. 4472–81. 2830495. 368131. 10.1128/MCB.7.12.4472.
  3. Thompson. CB. Lindsten. T. Ledbetter. JA. Kunkel. SL. Young. HA. Emerson. SG. Leiden. JM. June. CH. 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. February 1989. 86. 4. 1333–7. 2465550. 286684. 10.1073/pnas.86.4.1333. 1989PNAS...86.1333T. free.
  4. Walunas. TL. Lenschow. DJ. Bakker. CY. Linsley. PS. Freeman. GJ. Green. JM. Thompson. CB. Bluestone. JA. CTLA-4 can function as a negative regulator of T cell activation.. Immunity. August 1994. 1. 5. 405–13. 7882171. 10.1016/1074-7613(94)90071-X.
  5. Boise. LH. Minn. AJ. Noel. PJ. June. CH. Accavitti. MA. Lindsten. T. Thompson. CB. CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL.. Immunity. July 1995. 3. 1. 87–98. 7621080. 10.1016/1074-7613(95)90161-2. free.
  6. Boise. LH. González-García. M. Postema. CE. Ding. L. Lindsten. T. Turka. LA. Mao. X. Nuñez. G. Thompson. CB. bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death.. Cell. 27 August 1993. 74. 4. 597–608. 8358789. 10.1016/0092-8674(93)90508-N. 2027.42/30629. 13542617. free.
  7. Sattler. M. Liang. H. Nettesheim. D. Meadows. RP. Harlan. JE. Eberstadt. M. Yoon. HS. Shuker. SB. Chang. BS. Minn. AJ. Thompson. CB. Fesik. SW. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis.. Science. 14 February 1997. 275. 5302. 983–6. 9020082. 10.1126/science.275.5302.983. 22667419.
  8. Web site: National Academy of Science . nas.nasonline.org.
  9. Lindsten. T. Ross. AJ. King. A. Zong. WX. Jeffrey Rathmell. 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. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues.. Molecular Cell. December 2000. 6. 6. 1389–99. 11163212. 3057227. 10.1016/S1097-2765(00)00136-2.
  10. Wei. MC. Zong. WX. Cheng. EH. Lindsten. T. Panoutsakopoulou. V. Ross. AJ. Roth. KA. MacGregor. GR. Thompson. CB. Korsmeyer. SJ. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death.. Science. 27 April 2001. 292. 5517. 727–30. 11326099. 3049805. 10.1126/science.1059108. 2001Sci...292..727W.
  11. Rathmell. JC. Vander Heiden. MG. Harris. MH. Frauwirth. KA. Thompson. CB. In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability.. Molecular Cell. September 2000. 6. 3. 683–92. 11030347. 10.1016/S1097-2765(00)00066-6. free.
  12. Vander Heiden. MG. Plas. DR. Rathmell. JC. Fox. CJ. Harris. MH. Thompson. CB. Growth factors can influence cell growth and survival through effects on glucose metabolism.. Molecular and Cellular Biology. September 2001. 21. 17. 5899–912. 11486029. 87309. 10.1128/MCB.21.17.5899-5912.2001.
  13. Lum. JJ. Bauer. DE. Kong. M. Harris. MH. Li. C. Lindsten. T. Thompson. CB. Growth factor regulation of autophagy and cell survival in the absence of apoptosis.. Cell. 28 January 2005. 120. 2. 237–48. 15680329. 10.1016/j.cell.2004.11.046. free.
  14. Wise. DR. DeBerardinis. RJ. Mancuso. A. Sayed. N. Zhang. XY. Pfeiffer. HK. Nissim. I. Daikhin. E. Yudkoff. M. McMahon. SB. Thompson. CB. 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. 2 December 2008. 105. 48. 18782–7. 19033189. 2596212. 10.1073/pnas.0810199105. 2008PNAS..10518782W. free.
  15. Selak. MA. Armour. SM. MacKenzie. ED. Boulahbel. H. Watson. DG. Mansfield. KD. Pan. Y. Simon. MC. Thompson. CB. Gottlieb. E. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase.. Cancer Cell. January 2005. 7. 1. 77–85. 15652751. 10.1016/j.ccr.2004.11.022. free.
  16. 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. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate.. Cancer Cell. 16 March 2010. 17. 3. 225–34. 20171147. 2849316. 10.1016/j.ccr.2010.01.020.
  17. 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. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation.. Cancer Cell. 14 December 2010. 18. 6. 553–67. 21130701. 4105845. 10.1016/j.ccr.2010.11.015.
  18. 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. IDH mutation impairs histone demethylation and results in a block to cell differentiation.. Nature. 15 February 2012. 483. 7390. 474–8. 22343901. 3478770. 10.1038/nature10860. 2012Natur.483..474L.
  19. Web site: Leadership Board or Directors, Founders, Scientific Advisors Agios. www.agios.com. 26 July 2017. en.
  20. Web site: Thompson. Craig B.. June. Carl H.. Methods of treating autoimmune disease via CTLA-4Ig. 27 July 2017. 2004.
  21. Web site: June. Carl H.. Thompson. Craig B.. Nabel. Gary J.. Gray. Gary S.. Rennert. Paul D.. Freeman. Gordon J.. Methods for selectively stimulating proliferation of T cells. 27 July 2017. 1999.
  22. Web site: Davis. Ryan. Bristol-Myers Shells Out $21M To Settle Orencia Suit - Law360. www.law360.com. 27 July 2017. en.
  23. Web site: Apple. Sam. An Old Idea, Revived: Starve Cancer to Death. The New York Times. 26 July 2017. 12 May 2016.
  24. "News: Pollack. Andrew. Sloan-Kettering Chief Is Accused of Taking Research. 5 February 2012. The New York Times. 6 September 2012.
  25. News: Pollack. Andrew. Suits That Accused Sloan-Kettering Chief of Stealing Research Are Settled. 31 August 2012. nytimes.com. 6 September 2012.
  26. News: Mytelka. Andrew. Penn and Cancer Institute Settle Lawsuits Accusing Scientist of Stealing Research. 1 September 2012. The Chronicle of Higher Education. 6 September 2012.
  27. Web site: Medical Advisory Board. HHMI.org. 17 May 2017. en.
  28. Web site: Foundation. Lasker. 2016 Lasker Awards The Lasker Foundation. The Lasker Foundation. 17 May 2017. en.
  29. Web site: Editorial Board: Cell. www.cell.com. 17 May 2017. en.
  30. Web site: Masthead: Immunity. www.cell.com. 17 May 2017. en.
  31. Web site: Editorial Board: Cancer Cell. www.cell.com. 17 May 2017. en.
  32. Web site: Editors Cancer Discovery. cancerdiscovery.aacrjournals.org. 17 May 2017. en.
  33. Web site: Craig B. Thompson, MD. AACR.org. 26 May 2017.
  34. Web site: 09/19/06, Abramson Cancer Center Director: Craig Thompson - Almanac, Vol. 53, No. 4. www.upenn.edu. 26 May 2017.
  35. Web site: Medical Advisory Board. HHMI.org. 26 May 2017. en.
  36. Web site: Symposia on Cancer Research 2017. mdanderson.org. 26 May 2017.
  37. Web site: Symposium to Address Treatment and Prevention of Infectious Inflammatory and Oncogenic Disease - College of Medicine. College of Medicine. 5 June 2014. 26 May 2017. en.
  38. Web site: ACP National Award Recipients. American College Of Physicians. 13 June 2017. 5 August 2017. https://web.archive.org/web/20170805051721/https://www.acponline.org/system/files/documents/about_acp/awards_masterships/awards_2016.pdf. dead.
  39. Web site: Steven C. Beering Award Office of Faculty Affairs and Professional Development. faculty.medicine.iu.edu. 26 May 2017. en. https://web.archive.org/web/20180711051648/http://faculty.medicine.iu.edu/awards-services/awards/beering-award/. 11 July 2018. dead.
  40. Web site: Award & PhD Recipients Memorial Sloan Kettering Cancer Center. www.mskcc.org. 26 May 2017. en.
  41. Web site: Craig Thompson. www.nasonline.org. 26 May 2017.
  42. Web site: Recipients of Research Awards. med.upenn.edu. 26 May 2017.
  43. Web site: Craig B. Thompson, M.D.. nam.edu. 26 May 2017.
  44. Web site: Academy Member Connection. www.amacad.org. 26 May 2017. https://web.archive.org/web/20180303050514/https://www.amacad.org/peerCollaboration/profile.aspx?c=psa&q=craig_thompson. 3 March 2018. dead.
  45. Web site: The American Society for Clinical Investigation. www.the-asci.org. 26 May 2017.
  46. Web site: Association of American Physicians. aap-online.org. 13 June 2017.

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