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Tak Wah Mak

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The native form of thispersonal nameisMak Tak-wah.This article usesWestern name orderwhen mentioning individuals.
In thisChinese name,thefamily nameisMak.
Tak Wah Mak
Born
Mạch đức hoa, Mài Déhuá

(1946-10-04)October 4, 1946(age 78)[1][2]
Guangzhou,China
NationalityCanadian
Alma materWah Yan College, Kowloon
University of Wisconsin
University of Alberta
Known forDiscovery of theT-cell receptor

Discovery of the function ofCTLA-4

Founder ofAgios Pharmaceuticals
Scientific career
FieldsBiochemistry
Immunology
Biology
InstitutionsPrincess Margaret Cancer Centre
University Health Network
University of Toronto
Academic advisorsHoward Martin Temin
Ernest McCulloch
James Till

Tak Wah Mak,OCOOntFRSFRSC(simplified Chinese:Mạch đức hoa;traditional Chinese:Mạch đức hoa;pinyin:Mài Déhuá;born October 4, 1946, inChina) is a Canadian medical researcher, geneticist, oncologist, and biochemist. He first became widely known for his discovery of theT-cell receptorin 1983 and pioneering work in the genetics ofimmunology.[3]In 1995, Mak published a landmark paper on the discovery of the function of the immune checkpoint proteinCTLA-4,thus opening the path for immunotherapy/checkpoint inhibitors as a means of cancer treatment.[4]Mak is also the founder ofAgios Pharmaceuticals,whose lead compound, IDHIFA®, was approved by the FDA foracute myeloid leukemiain August 2017, becoming the first drug specifically targeting cancer metabolism to be used for cancer treatment.[5]He has worked in a variety of areas includingbiochemistry,immunology, and cancergenetics.

Early life

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Born in southern China in 1946 to parents who were silk merchants, and raised inHong Kong,parents encouraged him to become a doctor, his interests lay elsewhere—in math, biology, and chemistry.[6]Mak and his family moved to the United States of America during the mid-1960s and with the choice of going to theUniversity of Californiaor Wisconsin, he was persuaded by his mother to attend Wisconsin to avoid the antiwar activities at California. His interest in life and chemistry led him to eventually studying biochemistry and biophysics at the University of Wisconsin.

University life

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At theUniversity of Wisconsin,Mak met virologist Roland Rueckert.[6]Mak initially went to his lab to inquire about a job posting from Rueckert's lab looking for someone to wash test tubes.[6]After his first day on the job, Mak asked if more cleaning work was available, in which Rueckert said there was not, however there was experimental research work available. That, as Mak would later state, would be the beginning of his scientific career.[6]After finishing his degree at Wisconsin, Mak moved toCanadato begin his doctoral studies at theUniversity of Alberta,Edmonton.In the early 1970s, he earned his PhD in biochemistry from the University of Alberta. After he obtained his degree, Mak moved to Toronto and became a Canadian citizen. In Toronto, he worked withErnest McCullochandJames Till,who discovered haematopoietic stem cells.

Scientific career

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In 1980, Mak returned to Wisconsin to learn new techniques in the lab ofHoward Martin Temin,who won theNobel Prize in Physiology or Medicinein 1975 for his discovery of the enzymereverse transcriptase.[6]Temin would be one of his mentors that shaped his way of thinking, encouraging him to delve into diverse disciplines. During the early 1980s in Toronto, with his newly setup group, Mak was working on virology. Mak employed a technique called molecular subtraction, used by virologists, to attempt to identify the T-cell receptor, which was so elusive at the time it was referred to as the "Holy Grail of Immunology."[7]In 1984, Mak discovered the T-cell receptor, withMark M. Davisidentifying the receptor in mouse.[8]This work on thecloningofT-cellreceptor genes, as of 2005,has been cited nearly 1200 times. In spite of offers from prestigious institutions around the world, Mak remained committed to Canada's scientific community.

In 1993, Mak received support from the world's largest independent biotech company,Amgen,to establish theAmgenResearch Institute inToronto.Financial support fromAmgenresulted in his lab pioneering the use of knockout mice,[9]and as a result his lab generated one of the first knockout mice and has generated more knockout mice than any other lab in the world.[10]Mak's role in advancing the use ofgenetically alteredmice in scientific study has led to important breakthroughs in immunology and understanding cancer at the cellular level. As of 2005, Amgen-produced papers have been cited more than 40,000 times. The basic research incancerconducted by Mak has been published in top international scientific journals and he has given several keynote addresses at cancer symposia across Canada and the United States. By 1995, Mak had reached a high point in his career, when he and his team published their seminal findings on the function ofCTLA-4,[4]thus paving the road forImmunotherapyandCheckpoint inhibitionas potential anti-cancer therapies.

In 2004 Mak became the director of the Advanced Medical Discovery Institute and the Campbell Family Institute for Breast Cancer Research. He is also the senior scientist, division of Stem Cell and Developmental Biology, Advanced Medical Discovery Institute/Ontario Cancer Institute. He is a member of the Cancer Research Institute Scientific Advisory Council.[11]Since 1984, he has been a Professor in the Departments of Medical Biophysics and Immunology at theUniversity of Toronto.

From the early 2000s, Mak concentrated his efforts on the emerging field of cancer metabolism. Mak,Lewis C. Cantley,andCraig B. Thompsontogether foundedAgios Pharmaceuticals,a biotech pharmaceutical company whose sole purpose is to discover methods of targeting cancer metabolism. The trio have contributed immensely in a few years to what was originally a forgotten paradigm. The discovery of the involvement of particular enzymes such as PKM2, mutated IDH as well as novel oncometabolites such as 2-hydroxyglutarate in cancer development have once again brought cancer metabolism back to the forefront of cancer biology. On August 1,[year needed]Agios announced that the FDA had approved their lead compound, IDHIFA®, for the treatment of acute myeloid leukemia.[5]IDHIFA® targets a mutant form ofIsocitrate dehydrogenase2 and is the first[citation needed]drug specifically targeting cancer metabolism to be used for cancer treatment.

Mak holds Honorary Doctoral Degrees from numerous universities in North America and Europe. He is an Officer of theOrder of Canadaand has been elected a Foreign Associate of theNational Academy of Sciences(USA) as well as a Fellow of theRoyal Society of London(UK.) He has won international recognition in the forms of theEmil von Behring Prize,theKing Faisal Prize for Medicine,theGairdner Foundation International Award,theSloan Prizeof the General Motors Cancer Foundation, thePaul Ehrlich and Ludwig Darmstaedter Prize,theNovartis Prize in Immunology,and theSzent-Györgyi Prize for Progress in Cancer Research.

Honors

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Select publications[19]

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Year Title Publication Author(s) Volume/Issue Citation
2015 Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia Nature Chen Z, Shojaee S, Buchner M, Geng H, Lee JW, Klemm L, Titz B, Graeber TG, Park E, Tan YX, Satterthwaite A, Paietta E, Hunger SP, Willman CL, Melnick A, Loh ML, Jung JU, Coligan JE, Bolland S, Mak TW, Limnander A, Jumaa H, Reth M, Weiss A, Lowell CA, Müschen M. 10.1038/nature14231
1999 Glypican-3–Deficient Mice Exhibit Developmental Overgrowth and Some of the Abnormalities Typical of Simpson-Golabi-Behmel Syndrome The Journal of Cell Biology Cano-Gauci, D. F.; Song, H. H.; Yang, H.; McKerlie, C.; Choo, B.; Shi, W.; Pullano, R.; Piscione, T. D.; Grisaru, S.; Soon, S.; Sedlackova, L.; Tanswell, A. K.; Mak, T. W.; Yeger, H.; Lockwood, G. A.; Rosenblum, N. D.; Filmus, J. 10.1083/jcb.146.1.255
1984 A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains Nature Yanagi, Y.; Yoshikai, Y.; Leggett, K.; Clark, S. P.; Aleksander, I.; Mak, T. W. 10.1038/308145a0
1984 Presence of T-cell receptor mRNA in functionally distinct T cells and elevation during intrathymic differentiation Nature Yoshikai Y, Yanagi Y, Suciu-Foca N, Mak TW 10.1038/310506a0
1984 Rearrangements of T-cell receptor gene YT35 in human DNA from thymic leukaemia T-cell lines and functional T-cell clones Nature Toyonaga B, Yanagi Y, Suciu-Foca N, Minden M, Mak TW 10.1038/311385a0

References

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  1. ^"Science.ca: Tak Wah Mak".
  2. ^"Tak Wah Mak | Living History".Archived fromthe originalon 2016-03-04.Retrieved2014-02-23.
  3. ^Viegas, J. (2011)."Profile of Tak Wah Mak".Proceedings of the National Academy of Sciences.108(48): 19124–6.Bibcode:2011PNAS..10819124V.doi:10.1073/pnas.1116912108.PMC3228474.PMID22080609.
  4. ^abWaterhouse, Paul; Penninger, Josef M.; Timms, Emma; Wakeham, Andrew; Shahinian, Arda; Lee, Kelvin P.; Thompson, Craig B.; Griesser, Henrik; Mak, Tak W. (1995-11-10). "Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4".Science.270(5238): 985–988.Bibcode:1995Sci...270..985W.doi:10.1126/science.270.5238.985.ISSN0036-8075.PMID7481803.S2CID45993765.
  5. ^ab"FDA Grants Approval of IDHIFA®, the First Oral Targeted Therapy for Adult Patients with Relapsed/Refractory Acute Myeloid Leukemia and an IDH2 Mutation | Agios Pharmaceuticals, Inc. – IR Site".Agios Pharmaceuticals, Inc. – IR Site.Retrieved2017-08-04.
  6. ^abcdeJennifer, Viegas (29 November 2011)."Profile of Tak Wah Mak".Proceedings of the National Academy of Sciences.108(48). PNAS: 19124–19126.Bibcode:2011PNAS..10819124V.doi:10.1073/pnas.1116912108.PMC3228474.PMID22080609.
  7. ^Weiss, Arthur (2005)."Discovering the TCR β-Chain by Subtraction"(PDF).Journal of Immunology.175(5). The Journal of Immunology: 2769–2770.doi:10.4049/jimmunol.175.5.2769.PMID16116159.S2CID86549895.Retrieved25 March2019.
  8. ^Williams, Alan (1984)."The T -lymphocyte antigen receptor - elusive no more"(PDF).Nature.308(5955): 108–9.doi:10.1038/308108a0.PMID6608053.S2CID4318667.Retrieved21 April2013.
  9. ^Gura, Trisha (2001)."Toronto's science jewel".Nature.411(6837): 519–520.Bibcode:2001Natur.411..519G.doi:10.1038/35079195.PMID11385533.S2CID5115476.
  10. ^"Archived".Archived fromthe originalon 6 October 2014.Retrieved16 April2023.[dead link]
  11. ^Cancer Research Institute Scientific Advisory Council List
  12. ^"Steacie Prize Recipient List".E.W.R. Steacie Memorial Fund.Retrieved17 October2022.
  13. ^"Prize Winners since 1952".goethe-university-frankfurt.de.Goethe University Frankfurt.Retrieved17 October2022.
  14. ^"Tak Wah Mak–American Academy of Arts and Sciences".July 2023.
  15. ^"Order of Ontario 2007 Appointees".
  16. ^"Canadas Top 25 Immigrants 2015".Canadian Immigrant.Retrieved2021-06-18.
  17. ^"2021 Szent-Györgyi Prize Awarded to Pioneering Research Duo Who Have Paved the Path to Life-Saving T-Cell Receptor-Based Cancer Immunotherapies".National Foundation for Cancer Research.18 February 2021.Retrieved24 February2021.
  18. ^Picard, Andre (13 March 2023)."Canadian doctor Tak Mak wins prestigious award for pioneering work in cancer research".Globe and Mail. Archived fromthe originalon 14 March 2023.Retrieved14 March2023.
  19. ^"Mak TW PubMed Publications".Retrieved9 December2020.
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