BBS Faculty Member - Nicholas Dyson

Nicholas Dyson

Department of Medicine

Massachusetts General Hospital Cancer Center
Cancer Ctr., CNY Bldg.149, Rm. 7.330A
149 13th Street
Charlestown, MA 02129
Tel: 617-726-7804
Fax: 617-726-7808
Email: dyson@helix.mgh.harvard.edu
Lab Members: 6 postdoctoral fellows
Visit my lab page here.



My laboratory studies the mechanisms that limit cell proliferation in normal cells and the ways that these controls are eroded in cancer cells.

Our research focuses on the E2F transcription factor and the retinoblastoma tumor suppressor (RB). E2F controls the expression of a large number of target genes that are needed for cell proliferation. This transcriptional program is activated when normal cells are instructed to divide but it is deregulated in tumor cells, where it provides a cellular environment that is permissive for uncontrolled proliferation. pRB has multiple functions, but one of its most important roles is to limit the activity of E2F; as a result, most tumor cells select for changes that remove this control.

Our current goals are threefold. First, since pRB physically interacts with multiple proteins we are profiling these interactions and testing the idea that RB-family members link the local regulation of promoter regions with a more general organization of chromosome structure. Second, using screening approaches, we are learning how to selectively kill cells that lack RB function and have deregulated E2F activity. We want to obtain a comprehensive picture of the pathways and genes that impact E2F activity, and that affect E2F regulation by pRB. Third, we have taken advantage of the fact that Drosophila has a streamlined version of the mammalian RB/E2F families of proteins. We have used this simplified system to define the roles of individual components, and to carry out genetic screens for interacting pathways that are important in vivo.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Manning AL, Longworth MS, Dyson NJ. Loss of pRB causes centromere dysfunction and chromosomal instability. Genes and Development, 2010, 24(13):1364-76.

Distefano L, Walker JA, Burgio G, Corona DF, Mulligan P, Näär AM, Dyson NJ. Functional antagonism between histone H3K4 demethylases in vivo. Genes and Development, 2011 25(1):17-28.

Tschöp K, Conery AR, Litovchick L, DeCaprio JA, Settleman J, Harlow E and Dyson N. A kinase shRNA screen links LATS2 and the pRb tumor suppressor pathway. Genes and Development, 2011; 25(8):814-30.



© 2013 by the President and Fellows of Harvard College