Svetlana Mojsov

Last updated
Svetlana Mojsov
Светлана Мојсов
Born8 December 1947
Skopje, Macedonia. Yugoslavia
Nationality American
Alma mater Rockefeller University
Spouse Michel C. Nussenzweig
Father Lazar Mojsov
Awards2023 VinFuture
2023 Nature's 10
2023 Time100 Health
2024 Pearl Meister Greengard Prize
2024 Time 100 Most Influential People
2024 Princess of Asturias Awards
2024 Tang Prize - Biopharmaceutical Science
2024 Lasker Award
2025 Warren Triennial Prize
Scientific career
Fields Biochemistry, Peptide synthesis
Institutions Massachusetts General Hospital
Rockefeller University
Thesis Studies on solid-phase peptide synthesis: the synthesis of glucagon  (1978)

Svetlana Mojsov is a Macedonian American, ex-Yugoslavian-born chemist who is a research associate professor at Rockefeller University. Her research considers peptide synthesis. She discovered the glucagon-like peptide-1 and uncovered its role in glucose metabolism and the secretion of insulin. Her breakthroughs were transformed by Novo Nordisk into therapeutic agents against diabetes and obesity.

Contents

Early life and education

Mojsov was born in Skopje, Macedonia, ex-Yugoslavia and did her undergraduate degree in physical chemistry in Belgrade. She joined the graduate program at the Rockefeller University in 1972, where she worked alongside Robert Bruce Merrifield (1984 Nobel Prize in Chemistry) on the synthesis of peptides. [1] Specifically, Mojsov focused on the synthesis of glucagon, a hormone which is released by the pancreas. At the time it was proposed that glucagon might help to treat Type 2 diabetes.[ citation needed ]

Research and career

In the 1980s, Mojsov moved to the Massachusetts General Hospital, where she was made head of a peptide synthesis facility. She arrived at MGH shortly after Joel Habener had cloned proglucagon by studying anglerfish found in Boston Harbor. Mojsov worked on the identification of glucagon-like peptide-1 (GLP-1), a hormone generated by the gut that triggers the release of insulin. The amino acid sequence of GLP-1 was similar to a gastric inhibitory peptide, an incretin. To try to identify whether a specific fragment of GLP-1 was an incretin, Mojsov synthesized an incretin-antibody and developed ways to track its presence. Specifically, Mojsov identified that a stretch of 31 amino acids in the GLP-1 was an incretin. [2] [3] Together with Gordon Weir at the Joslin Diabetes Center in Boston and Habener, Mojsov showed that small quantities of lab-synthesized GLP-1 could trigger insulin. [4] [5]

In the 1990s, Mojsov returned to New York City, where she went back to Rockefeller University and the laboratory of Ralph M. Steinman (2011 Nobel Prize in Physiology or Medicine). In 1992, the group at Massachusetts General Hospital (MGH) using GLP-1 synthesized by Mojsov tested the GLP-1 in humans. [6] Drugs that emulate the action of GLP1 have been developed into treatments for obesity and diabetes by Novo Nordisk and Eli Lilly. [7] Eventually, the GLP-1 derivatives Mojsov synthesized were patented as peptides able to prompt the release of insulin, but with Joel Habener as the sole-creator. Mojsov fought to have her name included in patents, with MGH eventually agreeing to amend four patents to include her name and she received her one-third of drug royalties for one year. [8] She has continued to speak up for credit after her collaborators received various awards as new versions of GLP-1 have been approved and grown popular. [8] [9]

Prizes and awards

Selected publications

Personal life

At graduate school Mojsov met her future husband, Michel C. Nussenzweig.

Related Research Articles

<span class="mw-page-title-main">Glucagon</span> Peptide hormone

Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises the concentration of glucose and fatty acids in the bloodstream and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose. It is produced from proglucagon, encoded by the GCG gene.

Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.

<span class="mw-page-title-main">Incretin</span> Group of gastrointestinal hormones

Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.

<span class="mw-page-title-main">Gastric inhibitory polypeptide</span> Mammalian protein found in Homo sapiens

Gastric inhibitory polypeptide(GIP), also known as glucose-dependent insulinotropic polypeptide, is an inhibiting hormone of the secretin family of hormones. While it is a weak inhibitor of gastric acid secretion, its main role, being an incretin, is to stimulate insulin secretion.

Enteroglucagon is a peptide hormone derived from preproglucagon. It is a gastrointestinal hormone, secreted from mucosal cells primarily of the colon and terminal ileum. It consists of 37 amino acids. Enteroglucagon is released when fats and glucose are present in the small intestine; which decrease the motility to allow sufficient time for these nutrients to be absorbed.

<span class="mw-page-title-main">Exenatide</span> Medication

Exenatide, sold under the brand name Byetta among others, is a medication used to treat type 2 diabetes. It is used together with diet, exercise, and potentially other antidiabetic medication. It is a treatment option after metformin and sulfonylureas. It is given by injection under the skin.

<span class="mw-page-title-main">Vildagliptin</span> Chemical compound

Vildagliptin, sold under the brand name Galvus and others, is an oral anti-hyperglycemic agent of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas.

<span class="mw-page-title-main">Proglucagon</span> Protein that is cleaved from preproglucagon

Proglucagon is a protein that is cleaved from preproglucagon. Preproglucagon in humans is encoded by the GCG gene and is composed of 180 amino-acid residues.

<span class="mw-page-title-main">Glucagon-like peptide-1</span> Gastrointestinal peptide hormone involved in glucose homeostasis

Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.

<span class="mw-page-title-main">Glucagon-like peptide-1 receptor</span> Receptor activated by peptide hormone GLP-1

The glucagon-like peptide-1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of GPCRs. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.

<span class="mw-page-title-main">Gastric inhibitory polypeptide receptor</span> Protein-coding gene in the species Homo sapiens

The gastric inhibitory polypeptide receptor (GIP-R), also known as the glucose-dependent insulinotropic polypeptide receptor, is a protein that in humans is encoded by the GIPR gene.

Albiglutide is a glucagon-like peptide-1 agonist drug marketed by GlaxoSmithKline (GSK) for treatment of type 2 diabetes. As of 2017 it is unclear if it affects a person's risk of death. In 2017 GSK announced Albiglutide's withdrawal from the worldwide market for economic reasons, and remaining stocks in the supply chain were effectively depleted by 2018.

Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1DAs or incretin mimetics, are a class of anorectic drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating.

<span class="mw-page-title-main">Daniel J. Drucker</span> Canadian endocrinologist (born 1956)

Daniel Joshua Drucker is a Canadian endocrinologist. A Fellow of the Royal Society, he is a professor of medicine at the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto. He is known for his research into intestinal hormones and their use in the treatment of diabetes, obesity, and other metabolic diseases, as well as intestinal failure.

Joel Habener is a Professor of Medicine at Harvard Medical School.

MariTide, also known as maridebart cafraglutide, is an investigational drug developed by Amgen for the treatment of obesity. It is an agonist of the GLP-1 receptor (GLP-1R) and an antagonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR). Namely, MariTide consists of a monoclonal antibody against GIPR conjugated to two peptidic GLP-1R agonist molecules via amino acid linkers. In a preliminary trial, AMG 133 resulted in a 14.5 percent weight loss after 12 weeks at the highest dose tested.

Glucagon receptor agonists are a class of drugs under development for the treatment of obesity, non-alcoholic fatty liver disease, and congenital hyperinsulinism.

GLP1 poly-agonist peptides are a class of drugs that activate multiple peptide hormone receptors including the glucagon-like peptide-1 (GLP-1) receptor. These drugs are developed for the same indications as GLP-1 receptor agonists—especially obesity, type 2 diabetes, and non-alcoholic fatty liver disease. They are expected to provide superior efficacy with fewer adverse effects compared to GLP-1 mono-agonists, which are dose-limited by gastrointestinal disturbances. The effectiveness of multi-receptor agonists could possibly equal or exceed that of bariatric surgery. The first such drug to receive approval is tirzepatide, a dual agonist of GLP-1 and GIP receptors.

Lotte Bjerre Knudsen is a Danish scientist and university professor. She led the development of liraglutide and oversaw the development of semaglutide, two notable drugs approved for indications in the treatment of diabetes and obesity.

Jens Juul Holst is a Danish physician and physiologist. He is known for discovering and describing the hormone glucagon-like peptide-1 (GLP-1), a hormone in the gut that plays an important role in the onset and development of Type 2 diabetes. In collaboration with researcher and author Arne Astrup, he discovered that GLP-1 acts as a satiety hormone in humans.

References

  1. ↑ Mojsov, Svetlana; Merrifield, R. B. (December 1984). "An improved synthesis of crystalline mammalian glucagon". European Journal of Biochemistry. 145 (3): 601–605. doi:10.1111/j.1432-1033.1984.tb08599.x. ISSN   0014-2956. PMID   6510418.
  2. ↑ Mojsov, S. (1992). "Structural requirements for biological activity of glucagon-like peptide-I". International Journal of Peptide and Protein Research. 40 (3–4): 333–343. doi:10.1111/j.1399-3011.1992.tb00309.x. ISSN   0367-8377. PMID   1478791.
  3. ↑ Mojsov, S; Heinrich, G; Wilson, I B; Ravazzola, M; Orci, L; Habener, J F (September 1986). "Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing". Journal of Biological Chemistry. 261 (25): 11880–11889. doi: 10.1016/s0021-9258(18)67324-7 . ISSN   0021-9258. PMID   3528148.
  4. ↑ Mojsov, S; Weir, G C; Habener, J F (1987-02-01). "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.
  5. ↑ O’Rahilly, Stephen (2021-04-15). "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.
  6. ↑ Nathan, David M.; Schreiber, Eric; Fogel, Howard; Mojsov, Svetlana; Habener, Joel F. (1992). "Insulinotropic Action of Glucagonlike Peptide-I-(7–37) in Diabetic and Nondiabetic Subjects". Diabetes Care. 15 (2): 270–276. doi: 10.2337/diacare.15.2.270 . PMID   1547685 . Retrieved 2023-09-09.
  7. ↑ "Svetlana Mojsov". Our Scientists. Retrieved 2023-09-09.
  8. 1 2 Her work paved the way for blockbuster obesity drugs. Now, she's fighting for recognition (Report). 2023-09-08. doi:10.1126/science.adk7627.
  9. ↑ Molteni, Megan; Chen, Elaine (27 September 2023). "The Ozempic revolution is rooted in the work of Svetlana Mojsov, yet she's been edged out of the story". STAT. Retrieved 2023-10-09.
  10. ↑ "Laureates". VinFuture Prize. Retrieved 2024-04-20.
  11. ↑ "Nature's 10". www.nature.com. Retrieved 2024-02-29.
  12. ↑ "Svetlana Mojsov named 2024 recipient of the Pearl Meister Greengard Prize". News. Retrieved 2024-04-20.
  13. ↑ 2024 Pearl Meister Greengard Prize Ceremony . Retrieved 2024-04-23– via www.youtube.com.
  14. ↑ "Joel Habener, Svetlana Mojsov, and Dan Drucker: The 100 Most Influential People of 2024". TIME. 2024-04-17. Retrieved 2024-04-20.
  15. ↑ Princess of Asturias Awards 2024
  16. ↑ "Tang Prize | Laureates". www.tang-prize.org. Retrieved 2024-06-19.
  17. ↑ Admin, Lasker. "GLP-1-based therapy for obesity". Lasker Foundation. Retrieved 2024-09-20.
  18. ↑ Prashant Nair (19 September 2024). "QnAs with Svetlana Mojsov, Joel Habener, and Lotte Bjerre Knudsen: Winners of the 2024 Lasker~DeBakey Clinical Medical Research Award". Proceedings of the National Academy of Sciences of the United States of America . 121 (39). doi:10.1073/PNAS.2416868121. ISSN   0027-8424. Wikidata   Q130375905.
  19. ↑ "2025 Warren Triennial Prize". ecor.mgh.harvard.edu. Retrieved 2024-06-12.
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