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Carl Novina, MD, PhD

Associate Professor, Department of Microbiology and Immunobiology, Harvard Medical School

Contact Info

Carl Novina
Dana-Farber Cancer Institute
450 Brookline Avenue

Boston, MA, 02215
Mailstop: Dana 1420B
Phone: 617-582-7961
Fax: 617-582-7962


Not Available.

DF/HCC Program Affiliation

Cancer Immunology

Research Abstract

One of the most important advances in biology in the past decade was the discovery that double-strand RNA (dsRNA) molecules can silence gene expression. RNA interference (RNAi) is a natural phenomenon that is widely conserved across phyla and is a method of genome defense in lower eukaryotes. My laboratory focuses on the identification of endogenous short RNAs, their gene targets, the factors that catalyze silencing reactions and their regulators. Understanding the molecular details of RNAi will provide insights into the biological roles of short RNA-directed silencing in mammals. All short RNA-directed, gene-silencing phenomena require the assembly of a microribonucleoprotein complex (miRNP). In addition to identifying the factor requirements miRNP function, another way to understand the natural roles for RNAi in mammals is identifying endogenous short RNAs and their targeted mRNAs. An abundant class of ~22 nucleotide, non-coding RNAs called microRNAs (miRNAs) target as many as 33% of genes expressed in humans. Increasingly, evidence suggests that short RNAs regulate expression of genes required for normal lymphocyte development and function, a fact highlighted by the recent evidence that disruption of miRNA genes correlates with formation of certain cancers, including several leukemias and lymphomas.
We are working to identify miRNAs expressed in hematopoeitic cells, focusing primarily on normal and tumor-derived lymphocytes. We use bioinformatics approaches to predict mRNA targets of miRNAs cloned from B and T cells, and test the consequences of disrupting miRNP function in lymphocytes by transfecting specially modified 2-O-methylated oligonucleotides or by infecting with retroviruses expressing short RNAs that block endogenous miRNA function. By investigating the basic mechanisms of short RNA-directed gene silencing and identifying miRNA:mRNA pairs in normal and tumor-derived samples, we are interrogating the processes in B and T cell function naturally regulated by endogenous miRNAs.
For details on the biochemical, genomic and computational approaches used in my laboratory to investigate mammalian RNAi and its immune system-specific functions please visit http://research.dfci.harvard.edu/rnai.


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