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Daniel J. Drucker

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For other people called Daniel Drucker, see Daniel Drucker (disambiguation).

Daniel Drucker
FRS, FRCPC, OC
A white man in a suit standing next to an award
Dr. Daniel Drucker at the Princess of Asturias Awards ceremony in 2024
Born
Daniel Joshua Drucker

(1956-06-23) 23 June 1956 (age 68)[1]
Montreal, Quebec, Canada[1]
Alma materUniversity of Toronto (MD)[2]
Known forDiscovery of biological actions of GLP-1
Awards
Scientific career
Fields
Institutions
Website

Daniel Joshua Drucker (born 23 June 1956)[1] is a Canadian endocrinologist renowned for his breakthrough discoveries of the biological actions of glucagon-like peptides GLP-1 and GLP-2 including GLP-1's key role in stimulating glucose-dependant insulin secretion[3], reducing food intake[4] protecting the heart[5] and reducing systemic inflammation[6]. His scientific research has been a driving force in GLP-1's journey from a newly discovered peptide sequence to the mechanism behind globally used and life-changing therapeutics for type 2 diabetes and obesity. It has also driven transformative new therapeutics for intestinal failure and other metabolic disorders[7]. A Fellow of the Royal Society,[8] and laureate of the 2023 Wolf Prize in Medicine, he is a University Professor of Medicine at the University of Toronto and Senior Investigator at the Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto.

Early life and education

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Drucker was born and grew up in Montreal, went to high school in Ottawa, and then enrolled at the University of Ottawa, studying science.[9] In 1976, he moved to Toronto, where he studied medicine at the University of Toronto, graduating in 1980. He completed his internship at Johns Hopkins Hospital (1980–81), and completed his internal medicine and endocrinology residencies at the University of Toronto (1981–84).[9]

Career and research

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In 1984, Drucker began his research career at Massachusetts General Hospital and Harvard Medical School, studying molecular endocrinology in the lab of Professor Joel Habener with the support from a Medical Research Council of Canada Centennial Fellowship. Drucker’s independent discoveries in Boston included the demonstration that proglucagon could be cleaved into multiple glucagon-like peptides, including several distinct isoforms of GLP-1.[10] Along with Svetlana Mojsov, he then discovered that GLP-1(7-37) — a truncated form of GLP-1 identified previously by Mosjov as an incretin[11] — directly stimulated cyclic AMP formation, insulin secretion, and insulin gene expression; notably, it did so only when glucose levels were elevated.[3][12]

Further discoveries of the therapeutic potential of GLP-1 at University of Toronto

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In 1987 Drucker returned to Toronto, taking on the position of Assistant Professor of Medicine at the University of Toronto and continuing his research on the glucagon-like peptides while also working as a physician. In 1996, Drucker was one of several investigators who demonstrated that GLP-1 reduced food intake in preclinical studies. Notably, the experiments in the Drucker lab demonstrated that this action of GLP-1 in the brain required the functional canonical GLP-1 receptor.[4] Drucker, together with colleagues at Tufts Universities, filed multiple patents describing the utility of targeting the DPP-4 enzyme, and published studied demonstrating that genetic or chemical inactivation of DPP-4 prevented degradation of GLP-1 and GIP, supporting the development of DPP-4 inhibitors for the treatment of type 2 diabetes.[13][14] In all, Drucker's discovery science has led to 33 issued US patents supporting translational drug development efforts in the field of peptide based therapeutics. Collectively, the body of work from multiple investigators and companies led to the development of two leading classes of diabetes medications: GLP-1 receptor agonists and DPP4 inhibitors.[9]

Discovery of GLP-2 actions leading to Short Bowel Syndrome treatments

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In 1996, Drucker also discovered the first biological actions for GLP-2, demonstrating that it augmented crypt cell proliferation and expansion of the mucosal epithelium in the small bowel of mice and rats.[15] He subsequently identified and characterized a DPP-4-resistant molecule, teduglutide,[16] that was ultimately developed and approved for the treatment of short bowel syndrome in adults and children, a disorder in which fluids are poorly absorbed after resection of the small intestine.[9][17][18]

Research supporting the development, safety and benefits of GLP-1 therapeutics

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Drucker joined the Samuel Lunenfeld Research Institute at Mount Sinai Hospital in Toronto in 2006. In 2008 he led studies aimed at the development and testing of the first long-acting, once-weekly version of the diabetes medication exenatide.[19] He later studied the long-term effects of related weight-loss medicines on bowel health.[20] Drucker has also led the identification of the cardioprotective mechanisms of GLP-1 action. Notably, in 2009 he demonstrated in mice that these effects were not dependent on glucose lowering or weight loss[5] – findings confirmed over a decade later in cardiovascular outcome trials. His discoveries predicted the safety of GLP-1 receptor agonists for their expanding applications to treat obesity and other chronic conditions. Most recently, Drucker has identified multiple mechanisms linking GLP-1 to the reduction of inflammation[6][21].

He is a Canada Research Chair at the University of Toronto.

Awards and honours

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Drucker has received many national and international awards in recognition of his research accomplishments revealing the mechanisms of action and therapeutic potential of enteroendocrine hormones. These include the Prix Galien Canada for outstanding academic research (2008), the Donald F. Steiner Award for Outstanding Diabetes Research from the University of Chicago (2007), the Clinical Investigator Award from the Endocrine Society (2009), the Claude Bernard Prize from the European Association for the Study of Diabetes (2012), the Oon International Award and Lecture from the University of Cambridge (2014), the Banting Medal for Scientific Achievement from the American Diabetes Association (2014) the Manpei Suzuki Foundation International Prize for Diabetes (2014), and the Harold Hamm International Prize for Biomedical Research in Diabetes (2019). In 2021 he was awarded the Canada Gairdner International Award.[22] In 2023, he received the VinFuture Prize,[23] and also the Wolf Prize in Medicine "for pioneering work in elucidating the mechanisms and therapeutic potential of enteroendocrine hormones”.[24] In 2024 he was awarded the Princess of Asturias Awards for Technical and Scientific Research, as well as, the Golden Plate Award of the American Academy of Achievement.[25][26] Also in 2024 he received the BBVA Foundation Frontiers of Knowledge Award in the category "Biology and Biomedicine".[27]

Drucker was named an Officer of the Order of Canada in 2015.[28][29] He was elected a Fellow of the Royal Society (FRS) in 2015.[9][8] and was elected to the National Academy of Medicine in 2023.[30]

Selected publications

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References

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  1. ^ Jump up to: a b c "DRUCKER, Prof. Daniel Joshua". Who's Who. Vol. 2016 (online Oxford University Press ed.). Oxford: A & C Black. (Subscription or UK public library membership required.)
  2. ^ "Daniel J. Drucker M.D, FRCPC, Clinical Advisor, Diartis Pharmaceuticals, Inc". Bloomberg L.P. 16 February 2024.
  3. ^ Jump up to: a b Drucker, D J; Philippe, J; Mojsov, S; Chick, W L; Habener, J F (May 1987). "Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line". Proceedings of the National Academy of Sciences. 84 (10): 3434–3438. Bibcode:1987PNAS...84.3434D. doi:10.1073/pnas.84.10.3434. ISSN 0027-8424. PMC 304885. PMID 3033647.
  4. ^ Jump up to: a b Scrocchi, L.A.; Brown, T.J.; Maclusky, N.; Brubaker, P.L.; Auerbach, A.B.; Joyner, A.L.; Drucker, D.J. (November 1996). "Glucose intolerance but normal satiety in mice with a null mutation in the glucagon–like peptide 1 receptor gene". Nature Medicine. 2 (11): 1254–1258. doi:10.1038/nm1196-1254. ISSN 1078-8956. PMID 8898756. S2CID 41872654.
  5. ^ Jump up to: a b Noyan-Ashraf, Mohammad Hossein; Momen, M. Abdul; Ban, Kiwon; Sadi, Al-Muktafi; Zhou, Yu-Qing; Riazi, Ali M.; Baggio, Laurie L.; Henkelman, R. Mark; Husain, Mansoor; Drucker, Daniel J. (1 April 2009). "GLP-1R Agonist Liraglutide Activates Cytoprotective Pathways and Improves Outcomes After Experimental Myocardial Infarction in Mice". Diabetes. 58 (4): 975–983. doi:10.2337/db08-1193. ISSN 0012-1797. PMC 2661586. PMID 19151200.
  6. ^ Jump up to: a b Wong, Chi Kin; McLean, Brent A.; Baggio, Laurie L.; Koehler, Jacqueline A.; Hammoud, Rola; Rittig, Nikolaj; Yabut, Julian M.; Seeley, Randy J.; Brown, Theodore J.; Drucker, Daniel J. (January 2024). "Central glucagon-like peptide 1 receptor activation inhibits Toll-like receptor agonist-induced inflammation". Cell Metabolism. 36 (1): 130–143.e5. doi:10.1016/j.cmet.2023.11.009. PMID 38113888. S2CID 266371336.
  7. ^ Drucker, Daniel (2019). "The Discovery of GLP-2 and Development of Teduglutide for Short Bowel Syndrome". ACS Pharmacology & Translational Science. 2 (2): 134–142. doi:10.1021/acsptsci.9b00016. PMC 7088900. PMID 32219218.
  8. ^ Jump up to: a b "Professor Daniel Drucker FRS". London: The Royal Society. Archived from the original on 2 May 2015.
  9. ^ Jump up to: a b c d e Anon (2015). "Professor Daniel Drucker FRS". London: royalsociety.org. Archived from the original on 17 November 2015.
  10. ^ Drucker, D J; Mojsov, S; Habener, J F (July 1986). "Cell-specific post-translational processing of preproglucagon expressed from a metallothionein-glucagon fusion gene". Journal of Biological Chemistry. 261 (21): 9637–9643. doi:10.1016/s0021-9258(18)67561-1. ISSN 0021-9258. PMID 3525530.
  11. ^ Mojsov, S; Weir, G C; Habener, J F (1 February 1987). "Insulinotropin: glucagon-like peptide I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas". Journal of Clinical Investigation. 79 (2): 616–619. doi:10.1172/JCI112855. ISSN 0021-9738. PMC 424143. PMID 3543057.
  12. ^ O’Rahilly, Stephen (15 April 2021). "The islet's bridesmaid becomes the bride: Proglucagon-derived peptides deliver transformative therapies". Cell. 184 (8): 1945–1948. doi:10.1016/j.cell.2021.03.019. ISSN 0092-8674. PMID 33831374. S2CID 233131461.
  13. ^ Marguet, Didier; Baggio, Laurie; Kobayashi, Takashi; Bernard, Anne-Marie; Pierres, Michel; Nielsen, Per F.; Ribel, Ulla; Watanabe, Takeshi; Drucker, Daniel J.; Wagtmann, Nicolai (6 June 2000). "Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26". Proceedings of the National Academy of Sciences. 97 (12): 6874–6879. Bibcode:2000PNAS...97.6874M. doi:10.1073/pnas.120069197. ISSN 0027-8424. PMC 18768. PMID 10823914.
  14. ^ Hansotia, Tanya; Baggio, Laurie L.; Delmeire, Dominique; Hinke, Simon A.; Yamada, Yuichiro; Tsukiyama, Katsushi; Seino, Yutaka; Holst, Jens J.; Schuit, Frans; Drucker, D.J. (1 May 2004). "Double Incretin Receptor Knockout (DIRKO) Mice Reveal an Essential Role for the Enteroinsular Axis in Transducing the Glucoregulatory Actions of DPP-IV Inhibitors". Diabetes. 53 (5): 1326–1335. doi:10.2337/diabetes.53.5.1326. ISSN 0012-1797. PMID 15111503.
  15. ^ Drucker, D J; Erlich, P; Asa, S L; Brubaker, P L (23 July 1996). "Induction of intestinal epithelial proliferation by glucagon-like peptide 2". Proceedings of the National Academy of Sciences. 93 (15): 7911–7916. Bibcode:1996PNAS...93.7911D. doi:10.1073/pnas.93.15.7911. ISSN 0027-8424. PMC 38848. PMID 8755576.
  16. ^ Drucker, Daniel J.; Shi, Qing; Crivici, Anna; Sumner-Smith, Martin; Tavares, Wendy; Hill, Mary; DeForest, Lorraine; Cooper, Sari; Brubaker, Patricia L. (July 1997). "Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV". Nature Biotechnology. 15 (7): 673–677. doi:10.1038/nbt0797-673. ISSN 1087-0156. PMID 9219272. S2CID 35172107.
  17. ^ "Toronto endocrinologist named 2018 Principal Award winner by Manning Foundation". The Globe and Mail, Allan Maki, Calgary, 2 October 201
  18. ^ Harpain, Felix (2021). "Teduglutide in short bowel syndrome patients: A way back to normal life?". Journal of Parenteral and Enteral Nutrition. 46 (2): 300–309. doi:10.1002/jpen.2272. PMC 9298195. PMID 34614239.
  19. ^ "Study: Once-a-week diabetes drug works better than twice-daily injection". Scientific American News Blog, By Susannah F. Locke on 8 September 2008
  20. ^ "Researchers investigate possible colon cancer risk for new generation of weight-loss drugs".Science News, 3 March 2015
  21. ^ Wong, Chi Kin; Yusta, Bernardo; Koehler, Jacqueline A.; Baggio, Laurie L.; McLean, Brent A.; Matthews, Dianne; Seeley, Randy J.; Drucker, Daniel J. (October 2022). "Divergent roles for the gut intraepithelial lymphocyte GLP-1R in control of metabolism, microbiota, and T cell-induced inflammation". Cell Metabolism. 34 (10): 1514–1531.e7. doi:10.1016/j.cmet.2022.08.003. PMID 36027914.
  22. ^ Canada Gairdner International Award 2021
  23. ^ Nhu, Quynh (21 December 2023). "Battery researchers win $3M Vietnamese awards". VnExpress.
  24. ^ Wolf Prize in Medicine 2023
  25. ^ Princess of Asturias Awards 2024
  26. ^ "Golden Plate Awardees of the American Academy of Achievement". achievement.org. American Academy of Achievement.
  27. ^ BBVA Foundation Frontiers of Knowledge Award 2024
  28. ^ "Order of Canada ceremony invests 48 new recipients, including NBA star Steve Nash". CBC News, 13 May 2016
  29. ^ "Four Nova Scotians among Order of Canada honourees". The Chronicle-Herald, 1 July 2015.
  30. ^ "National Academy of Medicine Elects 100 New Members". National Academy of Medicine. 9 October 2023. Retrieved 9 October 2023.
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