Phillip A. Sharp

Phillip A. Sharp

Institute Professor and Professor of Biology; Member, Koch Institute for Integrative Cancer Research

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

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76-461A

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Email

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617-253-6425

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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 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. Divergent transcription from active promoters. Seila, AC, Calabrese, JM, Levine, SS, Yeo, GW, Rahl, PB, Flynn, RA, Young, RA, Sharp, PA. 2008. Science 322, 1849-51.
    doi: 10.1126/science.1162253PMID:19056940
  2. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Zamore, PD, Tuschl, T, Sharp, PA, Bartel, DP. 2000. Cell 101, 25-33.
    doi: 10.1016/S0092-8674(00)80620-0PMID:10778853
  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.
    PMID: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.
    PMID: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.
    PMID:269380

Recent Publications

  1. Gain-of-function mutation of microRNA-140 in human skeletal dysplasia. Grigelioniene, G, Suzuki, HI, Taylan, F, Mirzamohammadi, F, Borochowitz, ZU, Ayturk, UM, Tzur, S, Horemuzova, E, Lindstrand, A, Weis, MA et al.. 2019. Nat. Med. 25, 583-590.
    doi: 10.1038/s41591-019-0353-2PMID:30804514
  2. CDK12 regulates DNA repair genes by suppressing intronic polyadenylation. Dubbury, SJ, Boutz, PL, Sharp, PA. 2018. Nature 564, 141-145.
    doi: 10.1038/s41586-018-0758-yPMID:30487607
  3. Evolution of weak cooperative interactions for biological specificity. Gao, A, Shrinivas, K, Lepeudry, P, Suzuki, HI, Sharp, PA, Chakraborty, AK. 2018. Proc. Natl. Acad. Sci. U.S.A. 115, E11053-E11060.
    doi: 10.1073/pnas.1815912115PMID:30404915
  4. 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
  5. Deconvolution of seed and RNA-binding protein crosstalk in RNAi-based functional genomics. Suzuki, HI, Spengler, RM, Grigelioniene, G, Kobayashi, T, Sharp, PA. 2018. Nat. Genet. 50, 657-661.
    doi: 10.1038/s41588-018-0104-1PMID:29662165
  6. Mapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV-CRISPR-mediated direct in vivo screening. Wang, G, Chow, RD, Ye, L, Guzman, CD, Dai, X, Dong, MB, Zhang, F, Sharp, PA, Platt, RJ, Chen, S. 2018. Sci Adv 4, eaao5508.
    doi: 10.1126/sciadv.aao5508PMID:29503867
  7. Transcriptional Pause Sites Delineate Stable Nucleosome-Associated Premature Polyadenylation Suppressed by U1 snRNP. Chiu, AC, Suzuki, HI, Wu, X, Mahat, DB, Kriz, AJ, Sharp, PA. 2018. Mol. Cell 69, 648-663.e7.
    doi: 10.1016/j.molcel.2018.01.006PMID:29398447
  8. Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy. Nissim, L, Wu, MR, Pery, E, Binder-Nissim, A, Suzuki, HI, Stupp, D, Wehrspaun, C, Tabach, Y, Sharp, PA, Lu, TK. 2017. Cell 171, 1138-1150.e15.
    doi: 10.1016/j.cell.2017.09.049PMID:29056342
  9. Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma. Braun, CJ, Stanciu, M, Boutz, PL, Patterson, JC, Calligaris, D, Higuchi, F, Neupane, R, Fenoglio, S, Cahill, DP, Wakimoto, H et al.. 2017. Cancer Cell 32, 411-426.e11.
    doi: 10.1016/j.ccell.2017.08.018PMID:28966034
  10. Dicer loss and recovery induce an oncogenic switch driven by transcriptional activation of the oncofetal Imp1-3 family. JnBaptiste, CK, Gurtan, AM, Thai, KK, Lu, V, Bhutkar, A, Su, MJ, Rotem, A, Jacks, T, Sharp, PA. 2017. Genes Dev. 31, 674-687.
    doi: 10.1101/gad.296301.117PMID:28446596
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Photo credit: Evgenia Eliseeva