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Douglas A. Melton

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Doug Melton
Born
Douglas A. Melton
NationalityAmerican
Alma mater
Known forResearch on cure for type 1 diabetes
Awards
Scientific career
Fields
Institutions
ThesisThe expression of transfer RNA genes to other DNAs microinjected into Xenopus oocytes (1979)
Doctoral advisorJohn Gurdon[1]
Notable students
Website

Douglas A. Melton is an American medical researcher who is the Xander University Professor at Harvard University, and was an investigator at the Howard Hughes Medical Institute until 2022.[5] Melton serves as the co-director of the Harvard Stem Cell Institute and was the first co-chairman (with David Scadden) of the Harvard University Department of Stem Cell and Regenerative Biology. Melton is the founder of several biotech companies including Gilead Sciences, Ontogeny (now Curis), iPierian (now True North Therapeutics Archived 2017-06-29 at the Wayback Machine), and Semma Therapeutics. Melton holds membership in the National Academy of the Sciences,[6] the American Academy of Arts and Sciences, and is a founding member of the International Society for Stem Cell Research.[7]

Early life and education

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Melton grew up in Blue Island, Illinois[8] and completed a Bachelor of Science degree in biology at the University of Illinois at Urbana–Champaign in 1975.[9] He was awarded a Marshall Scholarship for study at the University of Cambridge where he received a Bachelor of Arts degree in the history and philosophy of science in 1977 and a PhD under the supervision of John Gurdon.[1][10]

Career and research

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Melton's early work was in general developmental biology, identifying genes important for cell fate determination and body pattern. This led to the finding that the nervous system in vertebrates is formed as a default when early embryonic cells do not receive inductive signals to become mesoderm or endoderm.[11] He also pioneered the technique of in vitro transcription with bacterial SP6 RNA polymerase.[12] This RNA transcription system is now widely used to make large amounts of messenger RNAs in vitro and is, for example, the basis for production of the COVID mRNA vaccines.

In the mid-1990s, work in his lab became centered on the development of the pancreas aiming to find new treatments for diabetes.

In 2001 when President George W. Bush cut federal funding of embryonic stem cell research, Melton used private donations to create 17 published[13][14] human stem cell lines and distributed them without charge to researchers around the world.

In August 2008, Melton's lab published successful in vivo reprogramming of adult mice exocrine pancreatic cells into insulin secreting cells which closely resembled endogenous islet beta cells of the pancreas in terms of their size, shape, ultrastructure, and essential marker genes.[15] Unlike producing beta cells from conventional embryonic stem cells or the more recently developed induced pluripotent stem cell (iPSC) technique, Melton's method involved direct cell reprogramming of an adult cell type (exocrine cell) into other adult cell type (beta cell) without reversion to a pluripotent stem cell state.

His current research interests include pancreatic developmental biology and the directed differentiation of human embryonic stem cells, particularly in pertinence to type 1 diabetes. In 2014, he reported a method using human pluripotent stem cells to generate virtually unlimited quantities of functional insulin-producing beta cells that respond appropriately to a glucose challenge.[16] This is considered a significant step forward in regenerative medicine for the possible treatment of diabetes, including type I diabetes, which afflicts both his children.

In 2022, Melton left Harvard University and joined Vertex Pharmaceuticals full-time to create diabetes treatments.[17]

Awards and honors

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Melton was elected a member of the National Academy of Sciences and the American Academy of Arts and Sciences in 1995. In 2007 and again in 2009, Melton was listed among the Time 100 Most Influential People in the World.[18] In 2016, Melton was awarded the Ogawa-Yamanaka Prize in Stem Cell Biology.[19] In 2023 he received the Abarca Prize for his advances towards a cure for diabetes.[20]

References

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  1. ^ a b J B Gurdon; D A Melton (1981). "Gene transfer in amphibian eggs and oocytes". Annual Review of Genetics. 15 (1): 189–218. doi:10.1146/ANNUREV.GE.15.120181.001201. ISSN 0066-4197. PMID 7039494. Wikidata Q28277421.
  2. ^ R P Harvey; D A Melton (3 June 1988). "Microinjection of synthetic Xhox-1A homeobox mRNA disrupts somite formation in developing Xenopus embryos". Cell. 53 (5): 687–97. doi:10.1016/0092-8674(88)90087-6. ISSN 0092-8674. PMID 2897242. Wikidata Q28283555.
  3. ^ M R Rebagliati; Daniel L Weeks; Richard P. Harvey; D A Melton (1 October 1985). "Identification and cloning of localized maternal RNAs from Xenopus eggs". Cell. 42 (3): 769–777. doi:10.1016/0092-8674(85)90273-9. ISSN 0092-8674. PMID 2414011. Wikidata Q28300491.
  4. ^ Kaspar Mossman (26 May 2009). "Profile of Clifford Tabin". Proceedings of the National Academy of Sciences of the United States of America. 106 (21): 8407–9. Bibcode:2009PNAS..106.8407M. doi:10.1073/PNAS.0903946106. ISSN 0027-8424. PMC 2688980. PMID 19458049. Wikidata Q28245644.
  5. ^ "Douglas A. Melton, PhD | Former Investigator Profile | 1994-2022".
  6. ^ Douglas A. Melton, Harvard University
  7. ^ Fox, Michael J. (May 3, 2007). "The 2007 Time 100: Douglas Melton". Time.
  8. ^ FitzPatrick, Lauren (June 3, 2007). "Time Will Tell - Scientist from Blue Island honored by Time Magazine". SouthtownStar. 37: a3.
  9. ^ Doug Melton's Curriculum Vitae
  10. ^ Melton, Douglas (1979). The expression of transfer RNA genes to other DNAs microinjected into Xenopus oocytes (PhD thesis). University of Cambridge.
  11. ^ Hemmati-Brivanlou A; Melton D (1 January 1997). "Vertebrate embryonic cells will become nerve cells unless told otherwise". Cell. 88 (1): 13–17. doi:10.1016/S0092-8674(00)81853-X. ISSN 0092-8674. PMID 9019398. Wikidata Q34415315.
  12. ^ D A Melton; P. A. Krieg; M. R. Rebagliati; T. Maniatis; K. Zinn; M. R. Green (25 September 1984). "Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter". Nucleic Acids Research. 12 (18): 7035–56. doi:10.1093/NAR/12.18.7035. ISSN 0305-1048. PMC 320141. PMID 6091052. Wikidata Q27861016.
  13. ^ Chad A. Cowan; Irina Klimanskaya; Jill McMahon; et al. (25 March 2004). "Derivation of Embryonic Stem-Cell Lines from Human Blastocysts". The New England Journal of Medicine. 350 (13): 1353–1356. doi:10.1056/NEJMSR040330. ISSN 0028-4793. PMID 14999088. S2CID 10575047. Wikidata Q29999326.
  14. ^ Derivation of Human Embryonic Stem Cells by Immunosurgery
  15. ^ Qiao Zhou; Juliana Brown; Andrew Kanarek; Jayaraj Rajagopal; Douglas A Melton (2 October 2008). "In vivo reprogramming of adult pancreatic exocrine cells to beta-cells". Nature. 455 (7213): 627–32. Bibcode:2008Natur.455..627Z. doi:10.1038/NATURE07314. ISSN 1476-4687. PMID 18754011. Wikidata Q28292190.
  16. ^ Felicia W Pagliuca; Jeffrey R Millman; Mads Gürtler; et al. (1 October 2014). "Generation of functional human pancreatic β cells in vitro". Cell. 159 (2): 428–439. doi:10.1016/J.CELL.2014.09.040. ISSN 0092-8674. PMC 4617632. PMID 25303535. Wikidata Q28249536.
  17. ^ "Douglas Melton, noted stem cell researcher, leaves Harvard for Vertex to create diabetes treatments". STAT. 2022-04-05. Retrieved 2022-04-05.
  18. ^ Michael J Fox (1 May 2007). "Time 100 scientists & thinkers. Douglas Melton". Time. 169 (20): 121. ISSN 0040-781X. PMID 17536327. Wikidata Q28304304.
  19. ^ PhD, Dana G. Smith (2016-09-27). "2016 Ogawa-Yamanaka Stem Cell Prize Awarded to Douglas Melton". Gladstone Institutes. Retrieved 2017-06-29.
  20. ^ Prize, Abarca. "PROF. DOUGLAS A. MELTON, WINNER OF THE III EDITION OF THE 'ABARCA PRIZE' FOR HIS DISRUPTIVE CURE OF TYPE 1 DIABETES, IS RECEIVED BY HIS MAJESTY THE KING OF SPAIN". www.prnewswire.com (Press release). Retrieved 2024-02-13.
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