Phillip A. Sharp

About

Phillip A. Sharp is an Institute Professor and Professor of Biology Emeritus at MIT, affiliated with the Koch Institute for Integrative Cancer Research. His research has focused on various aspects of gene expression in mammalian cells, including transcription, the roles of non-coding RNAs such as microRNAs, and RNA splicing. He has investigated small, non-coding RNAs called microRNAs (miRNAs), which regulate over half of the genes in mammalian cells at the stages of translation and mRNA stability. Additionally, his work explores the processes underlying transcription from the anti-sense strand, known as divergent transcription, as well as the relationship between transcription elongation, RNA splicing, and chromatin modifications. Throughout his career, Sharp has made significant contributions to understanding gene regulation mechanisms and has been recognized with numerous awards, including the Nobel Prize in Physiology or Medicine in 1993, the National Medal of Science in 2004, and the AACR Award for Lifetime Achievement in Cancer Research in 2020.

Research topics

• Biology
• Genetics
• Computer Science
• Biophysics
• Internal medicine
• Medicine
• Physics
• Cell biology
• Computational biology

Selected publications

• RNA-Mediated Feedback Control of Transcriptional Condensates

  Cell · 2020 · 614 citations

  PublisherOA PDFDOI

• Partitioning of cancer therapeutics in nuclear condensates

  Science · 2020 · 517 citations

  The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was als…

  PublisherOA PDFDOI

• RNA in formation and regulation of transcriptional condensates

  RNA · 2021-11-12 · 139 citations

  reviewOpen access1st author

  Macroscopic membraneless organelles containing RNA such as the nucleoli, germ granules, and the Cajal body have been known for decades. These biomolecular condensates are liquid-like bodies that can be formed by a phase transition. Recent evidence has revealed the presence of similar microscopic condensates associated with the transcription of genes. This brief article summarizes thoughts about the importance of condensates in the regulation of transcription and how RNA molecules, as components…

  PublisherOA PDFDOI

• Single-cell nascent RNA sequencing unveils coordinated global transcription

  Nature · 2024-06-05 · 108 citations

  articleOpen accessSenior author

  Abstract Transcription is the primary regulatory step in gene expression. Divergent transcription initiation from promoters and enhancers produces stable RNAs from genes and unstable RNAs from enhancers 1,2 . Nascent RNA capture and sequencing assays simultaneously measure gene and enhancer activity in cell populations 3 . However, fundamental questions about the temporal regulation of transcription and enhancer–gene coordination remain unanswered, primarily because of the absence of a single-ce…

  PublisherOA PDFDOI

• Oncogenic <i>CDK13</i> mutations impede nuclear RNA surveillance

  Science · 2023-04-20 · 53 citations

  articleOpen access

  RNA surveillance pathways detect and degrade defective transcripts to ensure RNA fidelity. We found that disrupted nuclear RNA surveillance is oncogenic. Cyclin-dependent kinase 13 ( CDK13 ) is mutated in melanoma, and patient-mutated CDK13 accelerates zebrafish melanoma. CDK13 mutation causes aberrant RNA stabilization. CDK13 is required for ZC3H14 phosphorylation, which is necessary and sufficient to promote nuclear RNA degradation. Mutant CDK13 fails to activate nuclear RNA surveillance, caus…

  PublisherOA PDFDOI

Recent grants

• Regulation of mRNA Processing

  NIH · $9.9M · 1984–2022

• Stress and Proliferation States Impact MicroRNA-Mediated Regulation in Cancer

  NIH · $4.6M · 2008–2019

• NIH Grant U54CA151884

  NIH · $8.9M · 2016

Frequent coauthors

• C. Collard

  Institut Pluridisciplinaire Hubert Curien

  236 shared

• J. Andreä

  Institut Pluridisciplinaire Hubert Curien

  235 shared

• E. Conte

  Institut Pluridisciplinaire Hubert Curien

  234 shared

• D. Blöch

  Institut Pluridisciplinaire Hubert Curien

  232 shared

• E. C. Chabert

  Institut Pluridisciplinaire Hubert Curien

  221 shared

• M. Lethuillier

  Institute of Nuclear Physics of Lyon

  212 shared

• B. Ille

  Institute of Nuclear Physics of Lyon

  191 shared

• P. Verdier

  Institute of High Energy Physics

  190 shared

Labs

• Phillip A. Sharp LabPI

Awards & honors

• AACR Award for Lifetime Achievement in Cancer Research (2020…
• AACR Distinguished Award for Extraordinary Scientific Innova…
• Royal Society of London, Foreign Fellow (2011)
• National Science Foundation, National Medal of Science (2004…
• The Nobel Foundation, Nobel Prize in Physiology or Medicine…

Similar researchers at Massachusetts Institute of Technology

• Rudolf Jaenischh-295
• Robert A. Weinbergh-291
• Susumu Tonegawah-237