Alexander Meissner

Department of Stem Cell and Regenerative Biology
Broad Institute
Bauer Laboratory

7 Divinity Avenue

Cambridge, MA 02138
Tel: (617) 495-8801
Fax: (617) 384-6891
Email: alexander_meissner@harvard.edu

Our lab is interested in the establishment, maintenance and regulation of epigenetic modifications during normal development and disease. Epigenetic marks are stable modifications of the DNA or chromatin that do not alter the nucleotide sequence. They provide regulatory information and can be read at a genomic scale using novel ultra high throughput sequencing technologies including high throughput bisulfite sequencing (HTBS) and chromatin immunopreciptitation followed by sequencing (ChIP-Seq). We focus on understanding the mechanism of how these modifications are regulated during normal development, how this regulation changes in diseases like cancer and how these marks are reset during epigenetic reprogramming by the oocyte, in the germline or artificially through nuclear transfer or ectopic expression of transcription factors (direct reprogramming). Recent work from our lab has provided first mechanistic insights into the generation of induced pluripotent stem (iPS) cells and highlighted several of the key roadblocks and how they can be overcome. This work on iPS cells further extends into our general interest of stem cell biology and pluripotency.

References:

Smith ZD, Nachman I, Regev A, Meissner A. Dynamic single-cell imaging of direct reprogramming reveals an early specifying event. Nat Biotechnol. 2010 May 2. [Epub ahead of print] PMID: 20436460
Gu H, Bock C, Mikkelsen TS, Jäger N, Smith ZD, Tomazou E, Gnirke A, Lander ES, Meissner A. Genome-scale DNA methylation mapping of clinical samples at single-nucleotide resolution. Nat Methods. 2010 Jan 10.
Amabile G, Meissner A. Induced pluripotent stem cells: current progress and potential for regenerative medicine. Trends Mol Med. 2009 Jan 20. PMID: 19162546
Mikkelsen TS., Hanna J., Zhang X., Ku M., Wernig M., Bernstein B.E., Jaenisch R., Lander ES., and Meissner A. Dissecting direct reprogramming through integrative genomic analysis. Nature. 2008 May 28 (online)

Meissner A, Mikkelsen T, Gnirke A, Gu H, Wernig M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Russ C, Nusbaum C, Jaenisch R and Lander ES. Genome-scale DNA methylation maps in pluripotent and differentiated cells. Nature. 2008 July 6 (online)
Meissner A, Wernig M and Jaenisch R. Direct Reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nature Biotechnology. 2007 Aug 27 (online).
Wernig M*, Meissner A,* Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE and Jaenisch R. In vitro reprogrammed fibroblasts have a similar developmental potential as ES cells and an ES cell-like epigenetic state. Nature. 2007 Jun 6 (online).

BBS webpage updated 5/18/2010