Phillip A. Sharp

ORCID: 0000-0003-1465-1691
Publications
Citations
Views
---
Saved
---
About
Contact & Profiles
Research Areas
  • RNA Research and Splicing
  • RNA and protein synthesis mechanisms
  • Virus-based gene therapy research
  • RNA modifications and cancer
  • RNA Interference and Gene Delivery
  • CRISPR and Genetic Engineering
  • MicroRNA in disease regulation
  • Genomics and Chromatin Dynamics
  • Particle physics theoretical and experimental studies
  • High-Energy Particle Collisions Research
  • Viral Infectious Diseases and Gene Expression in Insects
  • Quantum Chromodynamics and Particle Interactions
  • Bacteriophages and microbial interactions
  • Cancer-related molecular mechanisms research
  • Viral gastroenteritis research and epidemiology
  • Advanced biosensing and bioanalysis techniques
  • DNA and Nucleic Acid Chemistry
  • RNA regulation and disease
  • T-cell and B-cell Immunology
  • DNA Repair Mechanisms
  • Animal Genetics and Reproduction
  • HIV Research and Treatment
  • Particle Detector Development and Performance
  • Pluripotent Stem Cells Research
  • Polyomavirus and related diseases

Massachusetts Institute of Technology
2015-2024

Koch Institute for Integrative Cancer Research At MIT
2010-2021

Allen Institute
2010-2021

Centre for Human Genetics
2019

IIT@MIT
2009-2018

Imperial College London
2006-2015

Rutherford Appleton Laboratory
2011-2015

Tallahassee Memorial HealthCare
2014

Association for Asian Studies
2013

Nobel Foundation
2013

Developmental programs are controlled by transcription factors and chromatin regulators, which maintain specific gene expression through epigenetic modification of the genome. These regulatory events at enhancers contribute to that determine cell state potential for differentiation into new types. Although enhancer elements known be associated with certain histone modifications factors, relationship these developmental has not been clearly defined. Here we interrogate landscape in embryonic...

10.1073/pnas.1016071107 article EN Proceedings of the National Academy of Sciences 2010-11-24

10.1016/s0092-8674(00)80620-0 article EN publisher-specific-oa Cell 2000-03-01

Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density the transcriptional apparatus to drive robust expression genes with prominent roles in cell identity. Here we demonstrate SE-enriched coactivators BRD4 and MED1 form nuclear puncta at SEs exhibit properties liquid-like condensates disrupted by chemicals perturb condensates. The intrinsically disordered regions (IDRs) can phase-separated droplets, MED1-IDR droplets compartmentalize concentrate...

10.1126/science.aar3958 article EN Science 2018-06-21

MicroRNAs (miRNAs) are a class of noncoding RNAs found in organisms as evolutionarily distant plants and mammals, yet most the mRNAs they regulate unknown. Here we show that ability an miRNA to translationally repress target mRNA is largely dictated by free energy binding first eight nucleotides 5′ region miRNA. However, G:U wobble base-pairing this interferes with activity beyond predicted on basis thermodynamic stability. Furthermore, can be simultaneously repressed more than one species....

10.1101/gad.1184404 article EN Genes & Development 2004-03-01

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetection of two restriction endonuclease activities in Haemophilus parainfluenzae using analytical agarose-ethidium bromide electrophoresisPhillip A. Sharp, Bill Sugden, and Joe SambrookCite this: Biochemistry 1973, 12, 16, 3055–3063Publication Date (Print):July 1, 1973Publication History Published online1 May 2002Published inissue 1 July 1973https://pubs.acs.org/doi/10.1021/bi00740a018https://doi.org/10.1021/bi00740a018research-articleACS...

10.1021/bi00740a018 article EN Biochemistry 1973-07-01

Genome-wide genetic approaches have proven useful for examining pathways of biological significance in model organisms such as Saccharomyces cerevisiae, Drosophila melanogastor, and Caenorhabditis elegans, but similar techniques difficult to apply mammalian systems. Although manipulation the murine genome has led identification genes their function, this approach is laborious, expensive, often leads lethal phenotypes. RNA interference (RNAi) an evolutionarily conserved process gene silencing...

10.1261/rna.2192803 article EN RNA 2003-03-20

An mRNA fraction coding for hexon polypeptide, the major virion structural protein, was purified by gel electrophoresis from extracts of adenovirus 2-infected cells late in lytic cycle. The sequences this were mapped between 51.7 and 61.3 units on genome visualizing RNA-DNA hybrids electron microscope. When single-stranded restriction endonuclease cleavage fragments viral DNA visualized microscope,branched forms observed which 160 nucleotides RNA 5' terminus not hydrogen bonded to DNA....

10.1073/pnas.74.8.3171 article EN Proceedings of the National Academy of Sciences 1977-08-01

Messenger RNA (mRNA) stability, localization, and translation are largely determined by sequences in the 3' untranslated region (3'UTR). We found a conserved increase expression of mRNAs terminating at upstream polyadenylation sites after activation primary murine CD4+ T lymphocytes. This program, resulting shorter 3'UTRs, is characteristic gene during immune cell correlates with proliferation across diverse types tissues. Forced full-length 3'UTRs conferred reduced protein expression. In...

10.1126/science.1155390 article EN Science 2008-06-19

We have developed a cell-free system for studying the synthesis of mRNA in mammalian cells. The consists dialyzed and concentrated whole-cell extract derived from HeLa cells, small molecules cofactors needed transcription, exogenously added DNA. Accurate transcription by RNA polymerase II is entirely dependent upon addition promoter-containing eukaryotic At optimal DNA concentrations, initiation adenovirus serotype 2 late promoter readily detectable, specific transcripts over 4000...

10.1073/pnas.77.7.3855 article EN Proceedings of the National Academy of Sciences 1980-07-01

With the discovery of RNA interference (RNAi) and related phenomena, new regulatory roles attributed to continue emerge. Here we show, in mammalian tissue culture, that a short interfering (siRNA) can repress expression target mRNA with partially complementary binding sites its 3′ UTR, much like demonstrated function endogenously encoded microRNAs (miRNAs). The mechanism for this repression is cooperative, distinct from catalytic cleavage by siRNAs. use siRNAs study translational holds...

10.1101/gad.1064703 article EN Genes & Development 2003-02-15

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More

10.1146/annurev.bi.55.070186.005351 article EN Annual Review of Biochemistry 1986-06-01

10.1016/s1534-5807(03)00227-2 article EN publisher-specific-oa Developmental Cell 2003-08-01

Specific short oligonucleotide sequences that enhance pre-mRNA splicing when present in exons, termed exonic enhancers (ESEs), play important roles constitutive and alternative splicing. A computational method, RESCUE-ESE, was developed predicts which have ESE activity by statistical analysis of exon-intron splice site composition. When large data sets human gene were used, this method identified 10 predicted motifs. Representatives all motifs found to display enhancer vivo, whereas point...

10.1126/science.1073774 article EN Science 2002-08-09
Coming Soon ...