A new tool in the armamentarium of basic biomedical research, RNA interference, discovered in 1997 by UMass Medical School faculty member Craig Mello and his collaborators at the Carnegie Institution of Washington, uses double-stranded (ds) RNA to induce sequence-specific inhibition of gene function. In a variety of organisms, from model systems such as Drosophila and C.Elegans to HIV, researchers at UMass Medical School are using RNA interference to illuminate the very basic functioning of gene expression.

"The nice thing about RNA-based strategy is it’s the silver- bullet strategy where you can actually target the gene product itself that might be central to the disease."

Howard Hughes Medical Institute Investigator Craig C. Mello, PhD, associate professor of molecular medicine -- quoted in a December 16, 2002 feature in the Worcester Telegram & Gazette -- on the clinical and basic science potential of RNA interference (RNAi), a mechanism by which investigators can target and silence specific genes utilizing double- stranded RNA. In 2002, Dr. Mello and colleague Phillip D. Zamore, PhD, assistant professor of biochemistry & molecular pharmacology, were featured in a number of high-impact and local journals for their significant roles in the discovery related to this important mechanism. Described as having the potential to "prompt major advances in science," by an Aug. 6 Wall Street Journal feature in which Mello and Dr. Zamore were highlighted for their groundbreaking work, RNAi affords investigators major insight into human genetics with broad implications for drug discovery and design.

"Phillip Zamore is an outstanding young investigator whose efforts to understand the mechanistic basis of RNAi will enhance its applications to fundamental problems in biochemistry and to the treatment of a host of pathologies ranging from cancer to neurodegenerative diseases."

Chair of Biochemistry & Molecular Pharmacology C. Robert Matthews, PhD, the Arthur F. and Helen P. Koskinas Professor of Biochemistry & Molecular Pharmacology, praising the scientific mind of UMMS Assistant Professor of Biochemistry & Molecular Pharmacology Phillip D. Zamore, PhD, on the occasion of his selection as one of just five 2002 grant recipients under the W. M. Keck Foundation's Distinguished Young Scholars in Medical Research Program. Instituted in 1998, the Young Scholars Program is a five-year, $25 million initiative designed to support "groundbreaking research into the fundamental mechanisms of human disease by a select group of investigators who exhibit extraordinary promise early in their careers" and provides up to $1 million to support the scientist’s research activities for up to five years. Recruited to UMMS in 1999 from MIT’s Whitehead Institute for Biomedical Research, Dr. Zamore is studying one of the newest and most puzzling phenomena in basic science today: RNA interference (RNAi), or the ability of double-stranded RNA to “degrade” its homologous message when injected into cells, effectively turning off a targeted gene

Craig Mello
Phillip Zamore

• Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. "Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans." Nature. 1998 Feb 19;391(6669):806-11.
  
  
• Dianne S. Schwarz, György Hutvágner, Benjamin Haley, and Phillip D. Zamore.   "Evidence that siRNAs Function as Guides, Not Primers, in the Drosophila and Human RNAi Pathways." Molecular Cell, Sep 2002, 10 (3) 537-548
  
  
• Gyorgy Hutvagner and Phillip D. Zamore. "A microRNA in a Multiple Turnover RNAi Enzyme Complex"   Science vol. 297, no.5589   Pp. 2056-2060
  
  
• Xioaqiang Wang, Juanita McLachlan, Phillip D. Zamore , and Traci M. Tanaka Hall.  "Modular Recognition of RNA by a Human Pumilio-Homology Domain."  Cell.   110:501-512.   (August 23, 2002)
  
  
• Hiroaki Tabara, Erbay Yigit, Haruhiko Siomi, and Craig C. Mello .  "The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-Box helicase to direct RNAi in C. elegans."  Cell 109: 861-871.  (June 28, 2002 issue)