Douglas A. Melton
|Born||Douglas A. Melton
September 26, 1953
|Thesis||The expression of transfer RNA genes to other DNAs microinjected into Xenopus oocytes (1979)|
|Doctoral advisor||John Gurdon|
|Notable students||Richard P. Harvey (postdoc)|
|Known for||Research on cure for Type 1 diabetes|
Douglas A. Melton is the Xander University Professor at Harvard University, and an investigator at the Howard Hughes Medical Institute. Additionally, Melton serves as the co-director of the Harvard Stem Cell Institute and the co-chair of the Harvard University Department of Stem Cell and Regenerative Biology. Melton serves on the Scientific Advisory Board of the Genetics Policy Institute, holds membership in the National Academy of the Sciences, and is a founding member of the International Society for Stem Cell Research.
Melton completed a Bachelor of Science degree in Biology at the University of Illinois at Urbana–Champaign in 1975. He went on to study at the University of Cambridge where he was awarded a Bachelor of Arts degree in the History and Philosophy of Science in 1977. Under a Marshall Scholarship, Melton did his PhD at the University of Cambridge supervised by John Gurdon.
Career and Research
Melton's early work in the 1980s pioneered the technique of in vitro transcription. This later shifted to general developmental biology research in Xenopus, and eventually in the mid-1990s, became centered on the development of the pancreas.
In 2001 when President George W. Bush cut federal funding of embryonic stem cell research, Melton used private donations to create 17 published stem cell lines and distribute 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 pancreas in terms of their size, shape, ultrastructure and essential marker genes. Unlike producing beta cells from conventional embryonic stem cells or recently developed induced pluripotent stem cell (iPS) technique, Melton's unique method involved direct cell reprogramming of adult cell type (exocrine cell) into other adult cell type (beta cell) without reversion to a pluripotent stem cell state. His team used a specific combination of three transcription factors, Ngn3 (or Neurog3), Pdx1 and Mafa for such direct cell reprogramming to yield cells capable of secreting insulin and remodelling local vasculature in pancreas to counteract hyperglycemia and diabetes.
In 2013, the Melton group reported the discovery of Betatrophin, a hormone that signals the proliferation of insulin-producing Beta cells. After years of efforts to replicate the results, the report was eventually deemed false and the paper was retracted.
His current research interests include pancreatic developmental biology and the directed differentiation of human embryonic stem cells, particularly in pertinence to type 1 diabetes, which afflicts both his children.
Awards and honors
Melton was elected a member of the National Academy of Sciences and the American Academy of Arts and Sciences in 1995. In 2007 and 2009, Melton was listed among Time Magazine's 100 Most Influential People in The World.
- Doug Melton's Curriculum Vitae
- Gurdon, J. B.; Melton, D. A. (1981). "Gene transfer in amphibian eggs and oocytes". Annual Review of Genetics. 15: 189–218. doi:10.1146/annurev.ge.15.120181.001201. PMID 7039494.
- Harvey, R.P.; Melton, D.A. (1988). "Microinjection of synthetic Xhox-1A homeobox mRNA disrupts somite formation in developing Xenopus embryos". Cell. 53 (5): 687–697. doi:10.1016/0092-8674(88)90087-6. PMID 2897242.
- Rebagliati, M.R.; Weeks, D.L.; Harvey, R.P.; Melton, D.A. (1985). "Identification and cloning of localized maternal RNAs from xenopus eggs". Cell. 42 (3): 769–777. doi:10.1016/0092-8674(85)90273-9. PMID 2414011.
- Mossman, K. (2009). "Profile of Clifford Tabin". Proceedings of the National Academy of Sciences. 106 (21): 8407–8409. doi:10.1073/pnas.0903946106. PMC . PMID 19458049.
- Boyer, L. A.; Lee, T. I.; Cole, M. F.; Johnstone, S. E.; Levine, S. S.; Zucker, J. P.; Guenther, M. G.; Kumar, R. M.; Murray, H. L.; Jenner, R. G.; Gifford, D. K.; Melton, D. A.; Jaenisch, R.; Young, R. A. (2005). "Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells". Cell. 122 (6): 947–56. doi:10.1016/j.cell.2005.08.020. PMC . PMID 16153702.
- Klein, P. S.; Melton, D. A. (1996). "A molecular mechanism for the effect of lithium on development". Proceedings of the National Academy of Sciences of the United States of America. 93 (16): 8455–9. doi:10.1073/pnas.93.16.8455. PMC . PMID 8710892.
- Douglas A. Melton, Harvard University
- Douglas Melton - the Time 100
- Dor, Y.; Brown, J.; Martinez, O. I.; Melton, D. A. (2004). "Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation". Nature. 429 (6987): 41–46. doi:10.1038/nature02520.
- Melton, Douglas (1979). The expression of transfer RNA genes to other DNAs microinjected into Xenopus oocytes (PhD thesis). University of Cambridge.
- Melton, D. A.; Krieg, P. A.; Rebagliati, M. R.; Maniatis, T.; Zinn, K.; Green, M. R. (1984). "Efficientin vitrosynthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter". Nucleic Acids Research. 12 (18): 7035–7056. doi:10.1093/nar/12.18.7035.
- Cowan, C. A.; Klimanskaya, I.; McMahon, J.; Atienza, J.; Witmyer, J.; Zucker, J. P.; Wang, S.; Morton, C. C.; McMahon, A. P.; Powers, D.; Melton, D. A. (2004). "Derivation of Embryonic Stem-Cell Lines from Human Blastocysts". New England Journal of Medicine. 350 (13): 1353–1356. doi:10.1056/NEJMsr040330.
- Derivation of Human Embryonic Stem Cells by Immunosurgery
- Zhou, Q.; Brown, J.; Kanarek, A.; Rajagopal, J.; Melton, D. A. (2008). "In vivo reprogramming of adult pancreatic exocrine cells to β-cells". Nature. 455 (7213): 627–632. doi:10.1038/nature07314. PMID 18754011.
- Fox, M. J. (2007). "Time 100 scientists & thinkers. Douglas Melton". Time. 169 (20): 121. PMID 17536327.