Phillip A. Sharp

Phillip A. Sharp

Institute Professor and Professor of Biology; Intramural Faculty, Koch Institute

Phillip A. Sharp studies many aspects of gene expression in mammalian cells, including transcription, the roles of non-coding RNAs, and RNA splicing. 

617-253-6421

Phone

76-461A

Office

sharppa@mit.edu

Email

Koch Institute for Integrative Cancer Research

Location

Lab Website
Julia Liberman

Assistant

617-253-6425

Assistant Phone

Education

  • PhD, 1969, University of Illinois, Urbana-Champaign
  • BA, 1966, Chemistry and Math, Union College

Research Summary

We investigate 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. We are also interested in the processes underlying transcription from the anti-sense strand (so-called “divergent” transcription), as well as the relationship between elongation of transcription, RNA splicing, and chromatin modifications.

Awards

  • AACR Award for Lifetime Achievement in Cancer Research, 2020
  • AACR Distinguished Award for Extraordinary Scientific Innovation and Exceptional Leadership in Cancer Research and Biomedical Science, 2018
  • Royal Society of London, Foreign Fellow, 2011
  • National Science Foundation, National Medal of Science, 2004
  • The Nobel Foundation, Nobel Prize in Physiology or Medicine, 1993
  • National Academy of Medicine, Member, 1991
  • American Association for the Advancement of Science, Fellow, 1987
  • American Academy of Arts and Sciences, Fellow, 1987
  • National Academy of Sciences, Member, 1983

Key Publications

  1. Coactivator condensation at super-enhancers links phase separation and gene control. Sabari, BR, Dall'Agnese, A, Boija, A, Klein, IA, Coffey, EL, Shrinivas, K, Abraham, BJ, Hannett, NM, Zamudio, AV, Manteiga, JC et al.. 2018. Science 361, .
    doi: 10.1126/science.aar3958PMID:29930091
  2. A Phase Separation Model for Transcriptional Control. Hnisz, D, Shrinivas, K, Young, RA, Chakraborty, AK, Sharp, PA. 2017. Cell 169, 13-23.
    doi: 10.1016/j.cell.2017.02.007PMID:28340338
  3. Targeted mRNA degradation by double-stranded RNA in vitro. Tuschl, T, Zamore, PD, Lehmann, R, Bartel, DP, Sharp, PA. 1999. Genes Dev 13, 3191-7.
    doi: 10.1101/gad.13.24.3191PMID:10617568
  4. Splicing of adenovirus RNA in a cell-free transcription system. Padgett, RA, Hardy, SF, Sharp, PA. 1983. Proc Natl Acad Sci U S A 80, 5230-4.
    doi: 10.1073/pnas.80.17.5230PMID:6577417
  5. Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Berget, SM, Moore, C, Sharp, PA. 1977. Proc Natl Acad Sci U S A 74, 3171-5.
    doi: 10.1073/pnas.74.8.3171PMID:269380

Recent Publications

  1. Oncogenic CDK13 mutations impede nuclear RNA surveillance. Insco, ML, Abraham, BJ, Dubbury, SJ, Kaltheuner, IH, Dust, S, Wu, C, Chen, KY, Liu, D, Bellaousov, S, Cox, AM et al.. 2023. Science 380, eabn7625.
    doi: 10.1126/science.abn7625PMID:37079685
  2. Altered DNA repair pathway engagement by engineered CRISPR-Cas9 nucleases. Chauhan, VP, Sharp, PA, Langer, R. 2023. Proc Natl Acad Sci U S A 120, e2300605120.
    doi: 10.1073/pnas.2300605120PMID:36881621
  3. Transcription factor antagonism regulates heterogeneity in embryonic stem cell states. Hu, S, Metcalf, E, Mahat, DB, Chan, L, Sohal, N, Chakraborty, M, Hamilton, M, Singh, A, Singh, A, Lees, JA et al.. 2022. Mol Cell 82, 4410-4427.e12.
    doi: 10.1016/j.molcel.2022.10.022PMID:36356583
  4. RNA in formation and regulation of transcriptional condensates. Sharp, PA, Chakraborty, AK, Henninger, JE, Young, RA. 2022. RNA 28, 52-57.
    doi: 10.1261/rna.078997.121PMID:34772787
  5. RNA-Mediated Feedback Control of Transcriptional Condensates. Henninger, JE, Oksuz, O, Shrinivas, K, Sagi, I, LeRoy, G, Zheng, MM, Andrews, JO, Zamudio, AV, Lazaris, C, Hannett, NM et al.. 2021. Cell 184, 207-225.e24.
    doi: 10.1016/j.cell.2020.11.030PMID:33333019
  6. Partitioning of cancer therapeutics in nuclear condensates. Klein, IA, Boija, A, Afeyan, LK, Hawken, SW, Fan, M, Dall'Agnese, A, Oksuz, O, Henninger, JE, Shrinivas, K, Sabari, BR et al.. 2020. Science 368, 1386-1392.
    doi: 10.1126/science.aaz4427PMID:32554597
  7. MicroRNAs organize intrinsic variation into stem cell states. Chakraborty, M, Hu, S, Visness, E, Del Giudice, M, De Martino, A, Bosia, C, Sharp, PA, Garg, S. 2020. Proc Natl Acad Sci U S A 117, 6942-6950.
    doi: 10.1073/pnas.1920695117PMID:32139605
  8. Imprinted Maternally Expressed microRNAs Antagonize Paternally Driven Gene Programs in Neurons. Whipple, AJ, Breton-Provencher, V, Jacobs, HN, Chitta, UK, Sur, M, Sharp, PA. 2020. Mol Cell 78, 85-95.e8.
    doi: 10.1016/j.molcel.2020.01.020PMID:32032531
  9. Enhancer Features that Drive Formation of Transcriptional Condensates. Shrinivas, K, Sabari, BR, Coffey, EL, Klein, IA, Boija, A, Zamudio, AV, Schuijers, J, Hannett, NM, Sharp, PA, Young, RA et al.. 2019. Mol Cell 75, 549-561.e7.
    doi: 10.1016/j.molcel.2019.07.009PMID:31398323
  10. Pol II phosphorylation regulates a switch between transcriptional and splicing condensates. Guo, YE, Manteiga, JC, Henninger, JE, Sabari, BR, Dall'Agnese, A, Hannett, NM, Spille, JH, Afeyan, LK, Zamudio, AV, Shrinivas, K et al.. 2019. Nature 572, 543-548.
    doi: 10.1038/s41586-019-1464-0PMID:31391587
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Photo credit: Evgenia Eliseeva