Daniel J. Drucker

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Daniel Drucker
FRS , FRCPC , OC
Dr. Daniel Drucker at the Princess Asturias Awards ceremony in 2024.jpg
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 mater University 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.

Contents

Early life and education

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

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] He then discovered that the truncated form of GLP-1(7-37) directly stimulated cyclic AMP formation, insulin secretion, and insulin gene expression; notably, it did so only when glucose levels were elevated. [3] [11]

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

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 studies 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. [12] [13] 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

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. [14] He subsequently identified and characterized a DPP-4-resistant molecule, teduglutide, [15] 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] [16] [17]

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

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. [18] He later studied the long-term effects of related weight-loss medicines on bowel health. [19] 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] [20] .

Drucker holds the Banting and Best Diabetes Centre-Novo Nordisk Chair in Incretin Biology. His many national and international recognitions include the 2023 Wolf Prize in Medicine, awarded for "pioneering work in elucidating the mechanisms and therapeutic potential of enteroendocrine hormones," as well as the Warren Alpert Foundation Prize and the Canada Gairdner International Award, among numerous others. Drucker was elected a Royal Society Fellow in 2015, a National Academy of Sciences International Member in 2021and a National Academy of Medicine International Member in 2023. In 2024, he was named among Time magazine's 100 most influential people.

Awards and honours

Selected publications

References

  1. 1 2 3 "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. 1 2 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. 1 2 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. 1 2 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. 1 2 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. ↑ "Professor Daniel Drucker FRS". London: The Royal Society. Archived from the original on 2 May 2015.
  9. 1 2 3 4 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. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ "Toronto endocrinologist named 2018 Principal Award winner by Manning Foundation". The Globe and Mail, Allan Maki, Calgary, 2 October 201
  17. ↑ 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.
  18. ↑ "Study: Once-a-week diabetes drug works better than twice-daily injection". Scientific American News Blog, By Susannah F. Locke on 8 September 2008
  19. ↑ "Researchers investigate possible colon cancer risk for new generation of weight-loss drugs".Science News, 3 March 2015
  20. ↑ 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.
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