Douglas A. Melton

ORCID: 0000-0002-1623-5504
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About
Contact & Profiles
Research Areas
  • Pancreatic function and diabetes
  • Pluripotent Stem Cells Research
  • Diabetes and associated disorders
  • Congenital heart defects research
  • CRISPR and Genetic Engineering
  • Developmental Biology and Gene Regulation
  • Diabetes Management and Research
  • Animal Genetics and Reproduction
  • Renal and related cancers
  • RNA Research and Splicing
  • Genetics and Neurodevelopmental Disorders
  • Epigenetics and DNA Methylation
  • Metabolism, Diabetes, and Cancer
  • TGF-β signaling in diseases
  • Reproductive Biology and Fertility
  • 3D Printing in Biomedical Research
  • RNA Interference and Gene Delivery
  • Biomedical Ethics and Regulation
  • Tissue Engineering and Regenerative Medicine
  • RNA and protein synthesis mechanisms
  • RNA modifications and cancer
  • Mesenchymal stem cell research
  • Molecular Biology Techniques and Applications
  • Zebrafish Biomedical Research Applications
  • Single-cell and spatial transcriptomics

University of Missouri
2014-2024

Harvard University
2013-2023

Harvard Stem Cell Institute
2013-2023

Howard Hughes Medical Institute
2013-2023

Boston University
2020

Institute on Aging
2019

International Society for Stem Cell Research
2018

Institute of Semitic Studies
2018

Harvard University Press
1994-2013

College of the Atlantic
2011

A simple and efficient method for synthesizing pure single stranded RNAs of virtually any structure is described. This invitro transcription system based on the unusually specific RNA synthesis by bacteriophage SP6 polymerase which initiates exclusively at an promoter. We have constructed convenient cloning vectors that contain promoter immediately upstream from a polylinker sequence. Using these vectors, optimal conditions been established synthesis. The advantages uses derived as probes...

10.1093/nar/12.18.7035 article EN Nucleic Acids Research 1984-01-01

Lithium, one of the most effective drugs for treatment bipolar (manic-depressive) disorder, also has dramatic effects on morphogenesis in early development numerous organisms. How lithium exerts these diverse is unclear, but favored hypothesis that acts through inhibition inositol monophosphatase (IMPase). We show here complete IMPase no effect Xenopus embryos and present a different to explain broad action lithium. Our results suggest glycogen synthase kinase-3 beta (GSK-3 beta), which...

10.1073/pnas.93.16.8455 article EN Proceedings of the National Academy of Sciences 1996-08-06

The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for cells. A total 216 genes are enriched in all three types cells, several these clustered the genome. When differentiated cell types, express significantly higher number (represented by expressed sequence tags) whose functions unknown. Embryonic neural have many similarities at level. These results provide foundation more detailed understanding biology.

10.1126/science.1072530 article EN Science 2002-10-17

We describe a method for the synthesis of microgram quantities eucaryotic messenger RNAs. Injection into cytoplasm frog oocytes and addition to wheat germ extracts show that these synthetic RNAs function efficiently as confirm 5′ cap on mRNA is essential translation in injected most 3′ flanking region, including poly A tail, can be deleted without abolition protein synthesis. The involves invitro transcription cDNAs which have been cloned SP6 vectors (described accompanying paper). This...

10.1093/nar/12.18.7057 article EN Nucleic Acids Research 1984-01-01

The location and lineage of cells that give rise to endocrine islets during embryogenesis has not been established nor the origin or identity adult islet stem cells. We have employed an inducible Cre-ERTM-LoxP system indelibly mark progeny expressing either Ngn3 Pdx1 at different stages development. results provide direct evidence NGN3+ are progenitors in mice. In addition, we find all three types pancreatic tissue: exocrine, duct. Furthermore, exocrine derived from Pdx1-expressing...

10.1242/dev.129.10.2447 article EN Development 2002-05-15

Human embryonic stem (ES) cells are pluripotent derived from the inner cell mass of in vitro fertilized human blastocysts. We examined potential eight growth factors [basic fibroblast factor (bFGF), transforming β1 (TGF-β1), activin-A, bone morphogenic protein 4 (BMP-4), hepatocyte (HGF), epidermal (EGF), β nerve (βNGF), and retinoic acid] to direct differentiation ES-derived . show that ES have initiated development as aggregates (embryoid bodies) express a receptor for each these factors,...

10.1073/pnas.97.21.11307 article EN Proceedings of the National Academy of Sciences 2000-10-10

Blood vessels supply developing organs with metabolic sustenance. Here, we demonstrate a role for blood as source of developmental signals during pancreatic organogenesis. In vitro experiments embryonic mouse tissues that vessel endothelium induces insulin expression in isolated endoderm. Removal the dorsal aorta Xenopus laevis embryos results failure vivo. Furthermore, using transgenic mice, show ectopic vascularization posterior foregut leads to and islet hyperplasia. These indicate not...

10.1126/science.1064344 article EN Science 2001-10-19

Embryonic stem cells have the unique ability to form all adult cell types.Harnessing this potential may provide a source of replace those that are lost or impaired as result disease.Moreover, derivation human embryonic opens window into study early development.At present, approximately 15 stem-cell lines publicly available, and they vary considerably in their usefulness for research extent characterization (see http://stemcells.nih.gov/registry/index.asp).To promote further with cells, we...

10.1056/nejmsr040330 article EN New England Journal of Medicine 2004-03-24

Diurnal temperature range in winter wheat–growing regions of China: CMIP6 model evaluation and comparison,

10.1126/science.1077838 article EN Science 2003-01-17

We have explored the use of embryonic stem cells as an alternative to oocytes for reprogramming human somatic nuclei. Human (hES) were fused with fibroblasts, resulting in hybrid that maintain a stable tetraploid DNA content and morphology, growth rate, antigen expression patterns characteristic hES cells. Differentiation vitro vivo yielded cell types from each germ layer. Analysis genome-wide transcriptional activity, reporter gene activation, allele-specific expression, methylation showed...

10.1126/science.1116447 article EN Science 2005-08-25

ABSTRACT The gastrointestinal tract develops from the embryonic gut, which is composed of an endodermally derived epithelium surrounded by cells mesodermal origin. Cell signaling between these two tissue layers appears to play a critical role in coordinating patterning and organogenesis gut its derivatives. We have assessed function Sonic hedgehog Indian genes, encode members Hedgehog family cell signals. Both are expressed endoderm, whereas target genes discrete mesenchyme. It was unclear...

10.1242/dev.127.12.2763 article EN Development 2000-06-15

Multiple cell types of the pancreas appear asynchronously during embryogenesis, which requires that pancreatic progenitor potential changes over time. Loss-of-function studies have shown Notch signaling modulates differentiation these progenitors, but it remains unclear how and when pathway acts. We established a modular transgenic system to heritably activate mouse Notch1 in multiple progenitors differentiated cells. find misexpression activated Pdx1 -expressing cells prevents both exocrine...

10.1073/pnas.2436557100 article EN Proceedings of the National Academy of Sciences 2003-12-01

The mechanisms that regulate pancreatic β cell mass are poorly understood. While autoimmune and pharmacological destruction of insulin-producing cells is often irreversible, adult does fluctuate in response to physiological cues including pregnancy insulin resistance. This plasticity points the possibility harnessing regenerative capacity treat diabetes. We developed a transgenic mouse model study dynamics regeneration from diabetic state. Following doxycycline administration, mice expressed...

10.1172/jci32959 article EN Journal of Clinical Investigation 2007-09-04
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