Professional Education

  • Doctor of Philosophy, Univ of Massachusetts Medical School (2010)

Stanford Advisors


All Publications

  • DNA Demethylation Dynamics CELL Bhutani, N., Burns, D. M., Blau, H. M. 2011; 146 (6): 866-872


    The discovery of cytosine hydroxymethylation (5hmC) suggested a simple means of demethylating DNA and activating genes. Further experiments, however, unearthed an unexpectedly complex process, entailing both passive and active mechanisms of DNA demethylation by the ten-eleven translocation (TET) and AID/APOBEC families of enzymes. The consensus emerging from these studies is that removal of cytosine methylation in mammalian cells can occur by DNA repair. These reports highlight that in certain contexts, DNA methylation is not fixed but dynamic, requiring continuous regulation.

    View details for DOI 10.1016/j.cell.2011.08.042

    View details for Web of Science ID 000295258100010

    View details for PubMedID 21925312

  • CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation NATURE Burns, D. M., D'Ambrogio, A., Nottrott, S., Richter, J. D. 2011; 473 (7345): 105-U125


    Cytoplasmic polyadenylation-induced translation controls germ cell development, neuronal synaptic plasticity and cellular senescence, a tumour-suppressor mechanism that limits the replicative lifespan of cells. The cytoplasmic polyadenylation element binding protein (CPEB) promotes polyadenylation by nucleating a group of factors including defective in germline development 2 (Gld2), a non-canonical poly(A) polymerase, on specific messenger RNA (mRNA) 3' untranslated regions (UTRs). Because CPEB regulation of p53 mRNA polyadenylation/translation is necessary for cellular senescence in primary human diploid fibroblasts, we surmised that Gld2 would be the enzyme responsible for poly(A) addition. Here we show that depletion of Gld2 surprisingly promotes rather than inhibits p53 mRNA polyadenylation/translation, induces premature senescence and enhances the stability of CPEB mRNA. The CPEB 3' UTR contains two miR-122 binding sites, which when deleted, elevate mRNA translation, as does an antagomir of miR-122. Although miR-122 is thought to be liver specific, it is present in primary fibroblasts and destabilized by Gld2 depletion. Gld4, a second non-canonical poly(A) polymerase, was found to regulate p53 mRNA polyadenylation/translation in a CPEB-dependent manner. Thus, translational regulation of p53 mRNA and cellular senescence is coordinated by Gld2/miR-122/CPEB/Gld4.

    View details for DOI 10.1038/nature09908

    View details for Web of Science ID 000290218300040

    View details for PubMedID 21478871