BBS Faculty Member - Alexander Gimelbrant

Alexander Gimelbrant

Department of Cancer Biology, DFCI
Department of Genetics, HMS

Dana Farber Cancer Institute
Smith Building, Room 922 B
450 Brookline Ave.
Boston, MA 02215
Tel: 617-582-7326
Fax: 617-632-4770
Email: alexander_gimelbrant@dfci.harvard.edu
Lab Members: 2 postdoctoral fellows, 2 graduate students
Visit my lab page here.



One of the most fundamental questions in biology is how cells become functionally distinct during development, even though they carry identical genome copies. We are particularly interested in the role played in the establishment of cell identity by the choice of which allele, maternal or paternal, will be expressed in a given cell lineage. Mechanisms of this type control genes coding for immunoglobulins and olfactory receptors, and are crucial for the generation of cell diversity in the immune and nervous systems. We have shown that this type of allelic choice occurs with many hundreds of human genes, creating an extraordinary epigenetic diversity in cell populations.

Currently, we use and develop a variety of approaches, including allele-specific arrays and whole-transcriptome next-gen sequencing, in order to build a comprehensive map of allele-specific expression and the correlated chromatin states. This effort is under way in both human and mouse cells to gain an insight into the evolutionary context of allelic silencing. Of particular interest to us is the contribution of allelic inactivation to progression of malignancy; an epigenetic silencing of one allele is a functional equivalent of loss of heterozygosity, even as the genome is still apparently intact.

Another line of research is identification of the molecular mechanisms underlying the choice of active and inactive alleles. We are using stem cells to characterize the developmental plasticity of allele-specific expression. We are also developing mouse knock-in models for high-throughput loss of function screening of pathways that are involved in establishment and maintenance of epigenetically controlled allele-specific expression.



Last Update: 1/13/2014



Publications

For a complete listing of publications click here.

 


 

Lengner CJ*, Gimelbrant AA*, Erwin JA, Cheng AW, Guenther MG, Welstead GG, Alagappan R, Frampton GM, Xu P, Muffat J, Santagata S, Powers D, Barrett CB, Young RA, Lee JT, Jaenisch R, Mitalipova M. Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell. 2010 May 28;141(5):872-83 (* equal contribution)

Gimelbrant AA, Hutchinson JN, Thompson BR, Chess A. Widespread monoallelic expression on human autosomes. Science 2007; 318: 1136-40.

Gimelbrant AA, Chess A. An epigenetic state associated with areas of gene duplication. Genome Res 2006; 16:723-9.

Gimelbrant AA, Skaletsky H, Chess A. Selective pressures on the olfactory receptor repertoire since the human-chimpanzee divergence. Proc Natl Acad Sci/ /USA 2004; 101:9019-22.



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