Stem Cell Program Labs

The Gregory Lab

Dr. Richard Gregory is a Principal Investigator at Children's Hospital Boston and an Assistant Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School.

Richard I. Gregory, Ph.D., is Professor in the Departments of Biological Chemistry and Molecular Pharmacology, and Pediatrics at Harvard Medical School, and Principal Investigator in The Stem Cell Program in the Division of Hematolgy/Oncology at Boston Children’s Hospital. He is also Principal faculty member of The Harvard Stem Cell Institute, and co-Director and executive committee member of the Harvard Initiative for RNA Medicine.

Dr. Gregory received a Ph.D. from Cambridge University in 2001, and his postdoctoral work was performed at the Fox Chase Cancer Center and the Wistar Institute, Philadelphia. Dr. Gregory’s postdoctoral research focused on mechanisms of miRNA biogenesis and function, and was supported by a Jane Coffin Childs Research Fellowship. Since its establishment in 2006 research in the Gregory laboratory has focused on understanding molecular and cellular mechanisms controlling RNA biogenesis and decay and exploring the relevance of these pathways in stem cell pluripotency, mammalian development, and human disease. He was named a Pew Scholar, and a March of Dimes Basil O’Connor Scholar. He was Chair of the RNA mechanisms in cancer study section of the American Cancer Society, and is currently member of the scientific review council of the Pershing Square Cancer Research Alliance, and fellowship award selection committee of the Damon Runyon Cancer Research Foundation. Dr. Gregory is committed to exploiting the basic knowledge of RNA regulatory pathways for the discovery and development of new and effective therapies for cancer and for cancer and other diseases.

Gregory Lab Research Summary:

The laboratory research focus is to understanding mechanisms of RNA regulation in stem cells and disease. Our specialized research program bridges RNA biochemistry, stem cells, and cancer research and represents an innovative strategy and unique expertise that promises to provide fundamental mechanistic insight into the posttranscriptional control of miRNAs, messenger RNAs (mRNAs), and non-coding RNAs (ncRNAs), as well as to identify new therapeutic opportunities for human disease including cancer. We use embryonic stem cells (ESCs) and human cancer cell lines that are amenable to applying large-scale biochemical-, genetic-, and cell biological approaches to help elucidate these mechanisms. These developmentally regulated embryonic pathways can be reactivated in cancer where they promote oncogenesis.

Our ongoing and future work falls into three main areas: 1) Elucidating mechanisms of miRNA biogenesis and function in ESCs. 2) Studying the molecular, cellular, and developmental role of a newly identified ncRNA quality control pathway. 3) Exploring the mechanisms and relevance of the ‘epitranscriptome’ in stem cells and cancer. As pioneers studying several disease-relevant RNA-binding proteins and ribonucleases the lab is uniquely poised to make fundamental and groundbreaking discoveries that impact ESC biology, development, growth, and cancer. The lab is committed to exploiting the basic knowledge of RNA regulatory pathways for the discovery and development of new and effective therapies for cancer and for cancer and other diseases.

GREGORY LABORATORY STAFF

Robinson Triboulet, Post-doctoral Fellow

Peng Du, Post-doctoral Fellow

Shuibin Lin, Post-doctoral Fellow

Mehdi Pirouz, Post-doctoral Fellow

Junho Choe, Post-doctoral Fellow

Qi Liu, Post-doctoral Fellow

Sarah Dixon-Clarke, Post-doctoral Fellow

Carmen Rios, Research Assistant/Lab Manager

SELECTED PUBLICATIONS

Pirouz M, Du P, Munafò M, Gregory RI. Dis3l2-Mediated Decay Is a Quality Control Pathway for Noncoding RNAs. Cell Rep. 2016 Aug 16;16(7):1861-1873.

Lin S, Choe J, Du P, Triboulet R, Gregory RI. The m(6)A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells. Mol Cell. 2016 May 5;62(3):335-45.

Triboulet R, Pirouz M, Gregory RI. A Single Let-7 MicroRNA Bypasses LIN28-Mediated Repression. Cell Rep. 2015 Oct 13;13(2):260-6.

Du P, Wang L, Sliz P, Gregory RI. A Biogenesis Step Upstream of Microprocessor Controls miR-17∼92 Expression. Cell. 2015 Aug 13;162(4):885-99.

Lin S, Gregory RI. Identification of small molecule inhibitors of Zcchc11 TUTase activity. RNA Biol. 2015;12(8):792-800.

Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 2015 Jun;15(6):321-33. Review.

Thornton JE, Du P, Jing L, Sjekloca L, Lin S, Grossi E, Sliz P, Zon LI, Gregory RI. Selective microRNA uridylation by Zcchc6 (TUT7) and Zcchc11 (TUT4). Nucleic Acids Res. 2014 Oct;42(18):11777-91.

Mori M, Triboulet R, Mohseni M, Schlegelmilch K, Shrestha K, Camargo FD, Gregory RI. Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer. Cell. 2014 Feb 27;156(5):893-906.

Martinez NJ, Chang HM, Borrajo Jde R, Gregory RI. The co-chaperones Fkbp4/5 control Argonaute2 expression and facilitate RISC assembly. RNA. 2013 Nov;19(11):1583-93.

Chang HM, Triboulet R, Thornton JE, Gregory RI. A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway. Nature. 2013 May 9;497(7448):244-8.

Martinez NJ, Gregory RI. Argonaute2 expression is post-transcriptionally coupled to microRNA abundance. RNA. 2013 May;19(5):605-12.

Thornton JE, Chang HM, Piskounova E, Gregory RI. Lin28-mediated control of let-7 microRNA expression by alternative TUTases Zcchc11 (TUT4) and Zcchc6 (TUT7). RNA. 2012 Oct;18(10):1875-85.

Thornton JE, Gregory RI. How does Lin28 let-7 control development and disease? Trends Cell Biol. 2012 Sep;22(9):474-82. Review.

Chang HM, Martinez NJ, Thornton JE, Hagan JP, Nguyen KD, Gregory RI. Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation. Nat Commun. 2012 Jun 26;3:923.

Piskounova E, Polytarchou C, Thornton JE, LaPierre RJ, Pothoulakis C, Hagan JP, Iliopoulos D, Gregory RI. Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell. 2011 Nov 23;147(5):1066-79.

Hagan J.P., Piskounova E, Gregory R.I. Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. Nat Struct Mol Biol. 2009 16, 1021-5. PMID: 19713958.

Viswanathan S. R., Daley G. Q., and Gregory R. I., Selective Blockade of MicroRNA Processing by Lin-28. Science 2008; 320, 97-100. PMID: 18292307.

Giving

Spotlight

  • The stem cell-cancer connection

    Two fundamental processes in biology—stem cell generation and carcinogenesis—are closely related. Richard Gregory, PhD, a principal investigator in the Stem Cell Program at Children’s Hospital Boston, is studying the nature of this link, and uncovering new approaches to enhancing stem cell creation as well as ways to inhibit cancer.