BBS Faculty Member - Richard Gregory

Richard Gregory

Department of Biological Chemistry and Molecular Pharmacology

Boston Children's Hospital
Karp 9th Floor
1 Blackfan Circle
Boston, MA 02115
Tel: 617-919-2273
Fax: 617-730-0222
Lab Members: 6 postdoctoral fellows

RNA biogenesis and decay mechanisms in stem cells and disease

Our goal is to understand molecular and cellular mechanisms controlling RNA biogenesis and decay and to explore the relevance of these pathways in stem cell pluripotency, mammalian development, and human disease. Our specialized research program bridges RNA biochemistry/molecular biology and stem cell research is at the forefront of an exciting area of investigation focused on RNA regulation and we have made significant contributions to identifying and characterizing key molecular and cellular mechanisms of stem cell biology. Pluripotent embryonic stem cells (ESCs) have the capacity to differentiate into any specialized cell type and are of potential therapeutic value for numerous degenerative diseases. Identifying novel gene regulatory pathways required for ESC self-renewal and pluripotency will define the foundations of ESC biology and facilitate the effective manipulation of cell fates for novel therapeutic approaches. Moreover, ESCs provide the opportunity to study developmentally controlled gene regulatory pathways and are amenable to applying biochemical, genetic, and cell biological approaches to elucidate these mechanisms. Relatively little is known about the posttranscriptional mechanisms controlling ESC biology. Until now the lab has focused on elucidating mechanisms of microRNA (miRNA) regulation in ESCs. Our identification and characterization of the pluripotency factor LIN28 as a selective inhibitor of miRNA biogenesis in ESCs represents a clear example of how once separate fields of research are now converging. We are currently broadening the scope of our work to expand beyond miRNAs and study the mechanisms controlling RNA biogenesis and decay more broadly. Our innovative research strategy addresses areas that are new, unexplored, and poorly understood. As pioneers studying several disease-relevant RNA-binding proteins and ribonucleases in ESCs the lab is uniquely poised to make fundamental and groundbreaking discoveries. Our work will uncover basic mechanisms of how RNA regulatory pathways impact ESC biology, development, growth, cancer, and neurological disease. Ultimately we aim to exploit this understanding for the development of new therapeutic approaches for cancer and degenerative disease.

Last Update: 8/10/2015


For a complete listing of publications click here.



Chang H-M., Triboulet R., Thornton J. E,, Gregory R. I. (2013) A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway. Nature, 497, 244-8.

Mori, M., Triboulet, R., Mohseni, M., Schlegelmilc, K., Shrestha, K., Camargo, F. D.
Gregory, R. I., (2014). Hippo signaling regulates Microprocessor and links cell density-dependent miRNA biogenesis to cancer. Cell, 156, 893-906.

Du P., Wang L., Sliz P., and
Gregory R. I. (2015). A biogenesis step upstream of Microprocessor controls miR-17~92 expression. Cell (in press).

© 2015 by the President and Fellows of Harvard College