The Alt lab studies the mechanism and control of the programmed genomic DNA alterations that occur in lymphocytes. Namely, they study the V(D)J recombination reaction that assembles immunoglobulin (Ig) and T cell receptor (TCR) variable region exons from germline V, D, and J gene segments in developing B and T lymphocytes, the Ig heavy chain (IgH) class switch recombination (CSR) reaction that changes expressed IgH constant regions exons in mature B lymphocytes, and the somatic hypermutation process that introduces point mutations into IgH and IgL variable regions exons to allow selection of B cells that produce higher affinity antibodies. As second major focus of the Alt lab is the elucidation of general mechanisms that repair DNA double strand breaks (DSBs) by end joining and how this mode of repair maintains genomic integrity and suppresses chromosomal translocations and cancer. These two general areas of study are complementary, with basic mechanisms uncovered in V(D)J recombination and CSR providing fundamental insights into general DSB repair. For their studies, the lab uses a broad range basic approaches that include molecular genetics, biochemistry, cell biology, and genomics. They also based many of their studies on gene-targeted mutation and the generation of novel animal-based approaches and models. In recent years, the lab also used imaging approaches, and they recently have established a spinning disk confocal microscopy facility for 3D FISH and live cell imaging. A particular focus of their work in coming years is the development of novel cell-based, animal-based and imaging model systems to study mechanisms of oncogenic translocations associated with B and T cell lymphomas.
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Papers & Publications
Alt, F.W. (2007) From gene amplification to V(D)J recombination and back: A personal account of my early years in B cell biology. European Journal of Immunology 37, S138-147
Perlot, T., Li, G., and Alt, F.W. (2008) Antisense transcripts from immunoglobulin heavy chain locus V(D)J and switch regions. Proc. Natl. Acad. Sci. USA 105, 3843-38488 PMID: 18292225
Franco. S., Murphy, M.M., Li, G., Borjeson, T., Boboila, C., and Alt, F.W. (2008) DNA-PKcs and Artemis function in the end-joining phase of immunoglobulin heavy chain class switch recombination. J. Ex. Med. 205, 557-564 PMID: 18316419
Li, G., Alt, F.W., Cheng, H-L., Brush, J.W., Goff, P., Murphy, M.M., Franco, S., Zhang, Y. and Zha, S. Lymphocyte-specific compensation for XLF/Cernunnos end-joining functions in V(D)J recombination. Molecular Cell In Press
Basu, U., Wang, Y., and Alt, F.W. Evolution of Phosphorylation dependent Regulation of Activation Induced Cytidine Deaminase. Molecular Cell In Press |
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