BBS Faculty Member - Carl Novina

Carl Novina

Department of Microbiology and Immunobiology

Dana Farber Cancer Institute
Dana Building, Room 1420B
450 Brookline Avenue
Boston, MA 02215
Tel: 617-582-7961
Fax: 617-582-7962
Email: carl_novina@dfci.harvard.edu
Visit my lab page here.



The Novina Lab has been driven by two fundamental questions: (1) what is the mechanism by which microRNAs affect gene expression and (2) how does dysregulation of microRNA pathways influence oncogenesis? We use classical biochemistry, combinatorial biochemistry, systematic genomics, computational approaches and advanced technologies to develop a deeper understanding of the biology of RNAs and their altered functions in disease. By understanding biological processes at the most fundamental levels, we are gaining greater insights into disease processes and developing the tools to treat these diseases. Projects are available in the three general areas outlined below.

(1) The biology of microRNAs and lncRNAs and their disregulation in cancers. Genomic profiling of patient samples led to the identification non-coding RNAs with roles in melanoma tumor formation. We have developed unique tools and methods to study non-coding RNA activity in vitro, ex vivo and in vivo. We have on-going collaborations to study RNA-containing complexes in vitro by high-resolution microscopy, in model organisms, and in patient samples.

(2) The role of cellular heterogeneity in ribosomopathies and melanoma drug resistance. We found that reduced expression of ribosomal protein genes selectively increased translation of microRNA-targeted mRNAs. A rare group of genetic diseases called ribosomopathies is characterized by reduced ribosome biogenesis and function. Clinically, these patients present with congenital anomalies, bone marrow failure and cancer predisposition. It has been a long-standing mystery why these patients present with this constellation of clinical findings. Because microRNAs frequently target body patterning genes, differentiation and developmental genes and oncogenes, we may have identified the molecular pathogenesis of ribosomopathies. We are currently using single cell RNA-seq of Diamond Blackfan Anemia and Shwachman Diamond Syndrome patient bone marrows to investigate the mechanism by which reduced expression of ribosomal genes can promote cancers.

(3) Epigenetic Reprogramming of disease-relevant genes. Altered microRNA expression has been used to classify diseases and many microRNA genes exhibit aberrant promoter hypo- and hyper-methylation in cancers. To study the causes and consequences of inappropriate DNA methylation of microRNA and other disease-relevant genes, we are developing “epigenetic engineering” tools that will enable site-specific addition and removal of methyl groups on DNA. We envision that reprogramming the epigenetic state of any gene of interest may be the next frontier in gene therapy. Our platform can be adapted to a variety of human diseases. We are planning projects to repress oncogenes and induce tumor suppressors in a variety of cancers (e.g. melanomas and ovarian cancers) and to reprogram leukocytes for improved anti-cancer immunotherapy.



Last Update: 10/1/2014



Publications

For a complete listing of publications click here.

 


 

Akt-mediated phosphorylation of argonaute2 downregulates cleavage and upregulates translational repression of microRNA targets. Horman SR, Janas MM, Litterst C, Wang B, MacRae IJ, Sever MJ, Morrissey DV, Graves P, Luo B, Umesalma S, Qi HH, Miraglia LJ, Novina CD, Orth AP. Mol. Cell. 2013; 50: 356-367.

Reduced expression of ribosomal proteins relieves microRNA-mediated repression. Janas MM, Wang E, Love T, Harris AS, Stevenson K, Semmelmann K, Shaffer JM, Chen P-H, Doench JG, Yerramilli SVBK, Neuberg DS, Iliopoulos D, Housman DE, Burge CB, and
Novina CD. Mol Cell. 2012; 46: 171-186.

Alternative RISC assembly: binding and repression of microRNA-mRNA duplexes by human Ago proteins. Janas, MM, Wang B, Harris AS, Aguiar M, Shaffer J.M, Yerramilli SVBK, Behlke MA, Wucherpfennig KW, Gygi SP, Gagnon E, and
Novina CD. RNA, 2012; 18(11): 2041-2055.

Feed-forward microprocessing and splicing activities at a microRNA-containing intron. Janas MM, Khaled M, Schubert S, Bernstein JG, Golan D, Veguilla RA, Fisher DE, Shomron N, Levy C, and
Novina CD. PLoS Genet. 2011. (7)10:e1002330.

microRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells. Li S, Moffett HF, Lu J, Werner L, Zhang H, Ritz J, Neuberg D, Wucherpfennig KW, Brown JR,
Novina CD. PLoS ONE. 2011. 2011; Mar 8;6(3):e16956.

Repression of tumor suppressor miR-451 is essential for NOTCH1-induced oncogenesis in T-ALL.Li X, Sanda T, Look AT,
Novina CD, von Boehmer H. J. Exp. Med. 2011. 208(4):663-75.

Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma. Levy C, Khaled M, Iliopoulos D, Janas M, Schubert S, Pinner S, Chen P-H, Li S, Fletcher A, Yokoyama S, Scott KL, Garraway LA, Song JS, Granter SR, Turley SJ, Fisher DE, and
Novina CD. Mol. Cell. 2010. 40(5):841-9.



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