Chromosome Biology

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Danesh Moazed

Professor of Cell Biology
HHMI Investigator

Danesh Moazed, Ph.D., is a Professor and HHMI Investigator in the Department of Cell Biology at Harvard Medical School.  He is a member of the Harvard Biophysics Program and the Harvard Initiative for RNA Medicine (HIRM). He received his undergraduate and Ph.D. degrees from the University of California in Santa Cruz and performed postdoctoral studies at the University of California in San Francisco.

The Moazed lab studies how genes are silenced and how silencing is epigenetically inherited across generations.  The lab’s interests revolve around diverse pathways of heterochromatin-mediated gene silencing in yeast and mammalian cells.  Work in budding yeast focuses on the structure and function of a diverged and relatively simple form of heterochromatin, which requires only three Silent information regulator (“Sir”) proteins that form a histone deacetylase and chromatin-binding complex.  Work in fission yeast focuses on a conserved example of heterochromatin that requires the nuclear RNA interference (RNAi) machinery, other RNA processing pathways, Heterochromatin protein 1 (HP1) homologs, and histone-modifying enzymes.  In mammalian cells, the work is focused on HP1-mediated and other heterochromatin formation pathways.  The lab uses approaches ranging from genetics and genomics, biochemical purification and reconstitution, and structural biology for their studies.  Ultimately, the lab seeks to understand the conserved fundamental principles that govern the assembly, function, and epigenetic propagation of heterochromatin.

David Pellman

Margaret M. Dyson Professor of Pediatric Oncology (DFCI)
Professor of Cell Biology
HHMI Investigator

David Pellman, M.D. is the Margaret M. Dyson Professor of Pediatric Oncology at the Dana-Farber Cancer Institute, a Professor of Cell Biology at Harvard Medical School, an Investigator of the Howard Hughes Medical Institute, and the Associate Director for Basic Science at the Dana-Farber/Harvard Cancer Center.  He received his undergraduate and medical degrees from the University of Chicago.  During medical school, he did research at the Rockefeller University.  His postdoctoral fellowship was at the Whitehead Institute/Massachusetts Institute of Technology.

The Pellman Lab works on the mechanism of cell division and how certain cell division errors drive rapid genome evolution.  The normal processes studied in the laboratory have included spindle positioning and asymmetric cell division, the mechanism of spindle assembly and cytokinesis, and the mechanism of nuclear envelope assembly and how it is coordinated with chromosome segregation.  The mutational processes studied in David’s group are particularly important for cancer, but have relevance for genome evolution in other contexts.  Current projects include: the mechanism of a newly discovered mutational process called “chromothripsis”, how the architecture and integrity of the nuclear envelope impacts genome maintenance, and the role of cytoplasmic chromatin in triggering innate immune proinflammatory signaling. The lab uses a variety of approaches which include, molecular genetics, biochemistry, and imaging.  Currently there is a heavy emphasis on using a combination of live-cell imaging and single-cell genome sequencing developed in the lab (“Look-Seq”) to relate the consequences of cell division errors to genome alterations. 

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