Richard Gregory, PhD

Department	Stem Cell Program
Hospital Title:	Assistant Professor
Academic Title:	Principal Investigator
Phone:	617-919-2273
Fax:	617-730-0222
Email:	Richard Gregory
Location:	1 Blackfan Circle Boston, MA 02115

Research Overview

Stem cells hold great promise for the development of new approaches to combat disease. However, the molecular basis for stem cell self-renewal and differentiation remains incompletely understood. Our research provides novel insight into embryonic stem cell gene regulation, and may lead to new therapies to manipulate microRNAs. These studies are relevant to the treatment of cancer, diabetes, developmental disorders and numerous degenerative diseases.

Focus of Research

Research in the Gregory Laboratory is focused on understanding the molecular pathways of how small regulatory RNAs are generated, how they exert their gene regulatory function, their role in the self-renewal and pluripotency of embryonic stem (ES) cells, and their relevance to human disease. RNA interference (RNAi) describes the recently identified phenomenon whereby small non-coding RNAs can silence gene expression. It is emerging that cells possess a wide repertoire of tiny regulatory RNAs that are critical for a variety of biological pathways and can repress genes via numerous mechanisms. For posttranscriptional gene silencing, microRNAs (miRNAs), and small inhibitory RNAs (siRNAs), function as guide molecules inducing mRNA degradation or translational repression. In mammals, hundreds of miRNAs have been identified, and have been implicated in controlling diverse developmental pathways. Indeed, recent predictions indicate that over one third of all human genes are targeted by miRNAs.

The ongoing projects aim at addressing the mechanisms of miRNA biogenesis and function. We recently identified the developmentally regulated RNA-binding protein Lin28 as a selective inhibitor of a subset of miRNAs. Some of our current work aims to understand the mechanism of this regulatory pathway as well as the identification of novel regulators of miRNA biogenesis and function.

About Richard Gregory, PhD

Dr. Gregory received a PhD from Cambridge University, UK in 2001 studying genomic imprinting at the Babraham Institute. 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. He joined Children's Hospital and Harvard Medical School as an Assistant Professor in 2006. He was named a 2008 Pew Scholar.

Key Publications

• Viswanathan S. R., Daley G. Q., and Gregory R. I. Selective Blockade of MicroRNA Processing by Lin28. Science 2008; 320, 97-100. PMID: 18292307.
   
• Piskounova E., Viswanathan S. R., Janas, M., Lapierre R. J., Daley G. Q., Sliz P., and Gregory R. I. Determinants of microRNA processing inhibition by the developmentally regulated RNA-binding protein Lin28. Journal of Biological Chemistry 2008; 283, 21310-4. PMID: 18550544.
   
• Triboulet R., Chang H., LaPierre R. J., and Gregory R. I., Posttranscriptional control of DGCR8 expression by the Microprocessor. RNA 2009 15, 1005-11. PMID: 19383765.
   
• 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