Douglas A. Melton

Last updated
Doug Melton
Born
Douglas A. Melton
NationalityAmerican
Alma mater
Known forResearch on cure for type 1 diabetes
Awards
Scientific career
Fields
Institutions
Thesis The expression of transfer RNA genes to other DNAs microinjected into Xenopus oocytes  (1979)
Doctoral advisor John 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]

Contents

Early life and education

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

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

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]

Related Research Articles

<span class="mw-page-title-main">Stem cell</span> Undifferentiated biological cells that can differentiate into specialized cells

In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage. They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.

Transdifferentiation, also known as lineage reprogramming, is the process in which one mature somatic cell is transformed into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type. It is a type of metaplasia, which includes all cell fate switches, including the interconversion of stem cells. Current uses of transdifferentiation include disease modeling and drug discovery and in the future may include gene therapy and regenerative medicine. The term 'transdifferentiation' was originally coined by Selman and Kafatos in 1974 to describe a change in cell properties as cuticle producing cells became salt-secreting cells in silk moths undergoing metamorphosis.

<span class="mw-page-title-main">Blastulation</span> Sphere of cells formed during early embryonic development in animals

Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula is a hollow sphere of cells known as blastomeres surrounding an inner fluid-filled cavity called the blastocoel. Embryonic development begins with a sperm fertilizing an egg cell to become a zygote, which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoel is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form.

<span class="mw-page-title-main">Embryonic stem cell</span> Type of pluripotent blastocystic stem cell

Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the inner cell mass (embryoblast) using immunosurgery results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage have the same moral considerations as embryos in the post-implantation stage of development.

<span class="mw-page-title-main">Oct-4</span> Mammalian protein found in Homo sapiens

Oct-4, also known as POU5F1, is a protein that in humans is encoded by the POU5F1 gene. Oct-4 is a homeodomain transcription factor of the POU family. It is critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will cause differentiation of the cells.

<span class="mw-page-title-main">Organoid</span> Miniaturized and simplified version of an organ

An organoid is a miniaturised and simplified version of an organ produced in vitro in three dimensions that mimics the key functional, structural and biological complexity of that organ. They are derived from one or a few cells from a tissue, embryonic stem cells or induced pluripotent stem cells, which can self-organize in three-dimensional culture owing to their self-renewal and differentiation capacities. The technique for growing organoids has rapidly improved since the early 2010s, and The Scientist names it as one of the biggest scientific advancements of 2013. Scientists and engineers use organoids to study development and disease in the laboratory, drug discovery and development in industry, personalized diagnostics and medicine, gene and cell therapies, tissue engineering and regenerative medicine.

<span class="mw-page-title-main">Induced pluripotent stem cell</span> Pluripotent stem cell generated directly from a somatic cell

Induced pluripotent stem cells are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka and Kazutoshi Takahashi in Kyoto, Japan, who together showed in 2006 that the introduction of four specific genes, collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. Shinya Yamanaka was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent."

<span class="mw-page-title-main">PDX1</span> A protein involved in the pancreas and duodenum differentiation

PDX1, also known as insulin promoter factor 1, is a transcription factor in the ParaHox gene cluster. In vertebrates, Pdx1 is necessary for pancreatic development, including β-cell maturation, and duodenal differentiation. In humans this protein is encoded by the PDX1 gene, which was formerly known as IPF1. The gene was originally identified in the clawed frog Xenopus laevis and is present widely across the evolutionary diversity of bilaterian animals, although it has been lost in evolution in arthropods and nematodes. Despite the gene name being Pdx1, there is no Pdx2 gene in most animals; single-copy Pdx1 orthologs have been identified in all mammals. Coelacanth and cartilaginous fish are, so far, the only vertebrates shown to have two Pdx genes, Pdx1 and Pdx2.

Neurogenins, often abbreviated as Ngn, are a family of bHLH transcription factors involved in specifying neuronal differentiation. The family consisting of Neurogenin-1, Neurogenin-2, and Neurogenin-3, plays a fundamental role in specifying neural precursor cells and regulating the differentiation of neurons during embryonic development. It is one of many gene families related to the atonal gene in Drosophila. Other positive regulators of neuronal differentiation also expressed during early neural development include NeuroD and ASCL1.

<span class="mw-page-title-main">Neurogenin-3</span> Mammalian protein found in Homo sapiens

Neurogenin-3 (NGN3) is a protein that in humans is encoded by the Neurog3 gene.

<span class="mw-page-title-main">Cell potency</span> Ability of a cell to differentiate into other cell types

Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum, begins with totipotency to designate a cell with the most differentiation potential, pluripotency, multipotency, oligopotency, and finally unipotency.

Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor or unipotent – (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.

Directed differentiation is a bioengineering methodology at the interface of stem cell biology, developmental biology and tissue engineering. It is essentially harnessing the potential of stem cells by constraining their differentiation in vitro toward a specific cell type or tissue of interest. Stem cells are by definition pluripotent, able to differentiate into several cell types such as neurons, cardiomyocytes, hepatocytes, etc. Efficient directed differentiation requires a detailed understanding of the lineage and cell fate decision, often provided by developmental biology.

<span class="mw-page-title-main">Chromatin assembly factor 1</span>

Chromatin assembly factor-1 (CAF-1) is a protein complex — including Chaf1a (p150), Chaf1b (p60), and p48 subunits in humans, or Cac1, Cac2, and Cac3, respectively, in yeast— that assembles histone tetramers onto replicating DNA during the S phase of the cell cycle.

<span class="mw-page-title-main">Pancreatic progenitor cell</span>

Pancreatic progenitor cells are multipotent stem cells originating from the developing fore-gut endoderm which have the ability to differentiate into the lineage specific progenitors responsible for the developing pancreas.

<span class="mw-page-title-main">Richard Harvey (scientist)</span> Australian biologist

Richard Paul Harvey is a molecular biologist, the Sir Peter Finley professor of Heart Research at the University of New South Wales and Deputy Director and Head of the Developmental and Stem Cell Biology Division at the Victor Chang Cardiac Research Institute.

<span class="mw-page-title-main">Bradley Bernstein</span> Biologist

Bradley E. Bernstein is a biologist and Professor of Cell Biology at Harvard Medical School. He is Chair of the Department of Cancer Biology at the Dana–Farber Cancer Institute and the Director of the Broad Institute's Gene Regulation Observatory. He is known for contributions to the fields of epigenetics and cancer biology.

<span class="mw-page-title-main">Derrick Rossi</span> Canadian stem cell biologist

Derrick J. Rossi, is a Canadian stem cell biologist and entrepreneur. He is a co-founder of the pharmaceutical company Moderna.

<span class="mw-page-title-main">Yi Zhang (biochemist)</span> Chinese-American biochemist

Yi Zhang is a Chinese-American biochemist who specializes in the fields of epigenetics, chromatin, and developmental reprogramming. He is a Fred Rosen Professor of Pediatrics and professor of genetics at Harvard Medical School, a senior investigator of Program in Cellular and Molecular Medicine at Boston Children's Hospital, and an investigator of the Howard Hughes Medical Institute. He is also an associate member of the Harvard Stem Cell Institute, as well as the Broad Institute of MIT and Harvard. He is best known for his discovery of several classes of epigenetic enzymes and the identification of epigenetic barriers of SCNT cloning.

<span class="mw-page-title-main">Dorsal lip</span>

The dorsal lip of the blastopore is a structure that forms during early embryonic development and is important for its role in organizing the germ layers. The dorsal lip is formed during early gastrulation as folding of tissue along the involuting marginal zone of the blastocoel forms an opening known as the blastopore. It is particularly important for its role in neural induction through the default model, where signaling from the dorsal lip protects a region of the epiblast from becoming epidermis, thus allowing it to develop to its default neural tissue.

References

  1. 1 2 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. ↑ https://www.hhmi.org/scientists/douglas-melton
  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. Retrieved 2024-02-13.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.