Frederick W. Alt
Department of Genetics
HHMI/Children's Hospital/Immune Disease Institute
Karp 9th Floor, Room 09216
1 Blackfan Circle
Boston, MA 02115
Tel: (617) 919-2539
Fax: (617) 730-0948
Email: alt@enders.tch.harvard.edu
12 postdoctoral fellows, 3 graduate students, 1 visiting professor, 2 undergraduates, 3 visiting students
The broad focus of the Alt laboratory is the elucidation of mechanisms involved in maintenance of genomic stability in mammalian cells. More specifically, the laboratory studies the mechanism and control of antigen receptor variable region gene assembly (VDJ recombination) in developing B and T lymphocytes and the mechanism of immunoglobulin heavy chain class switch recombination (CSR) and somatic hypermutation in activated mature B lymphocytes. Studies of the regulation of these processes involve elucidation of signaling events that lead to their activation, as well as elucidation of genetic and epigenetic chromosomal processes that regulate them. Some studies employ biochemical approaches to elucidate molecular mechanisms by which the RAG endonuclease (RAG) and Activation Induced Deaminase (AID) function on DNA to initiate, respectively, VDJ recombination and CSR. Other mechanistic studies employ genetic and cytogenetic approaches to study the role of general DNA double strand break (DSB) response pathways in VDJ recombination and CSR, as well as the interplay of DNA repair and cell cycle checkpoint mechanisms in suppressing genomic instability and cancer. In this context, the laboratory has developed mouse models, based on conditional inactivation of DSB response and checkpoint genes, for B and T cell lymphomas and brain tumors. A major new area of research in the laboratory is the use of confocal imaging approaches to elucidate the organization of sequences in the nucleus in the context of programmed gene rearrangements and translocations. Standard laboratory approaches range from basic molecular genetics, biochemistry, cytogenetics, confocal imaging, and genomics to gene-targeted mutation and the generation of novel animal-based approaches and models.
Recent Graduate Student Rotation Projects.
1. Genetic and cytogenetic studies of the function of the IgH 3' regulatory region in promoting oncogenic translocations with the c-myc gene.
2. Genetic and biochemical elucidation of posttranslational AID modifications and interacting proteins.
3. Cytogenetic analyses of the role of DNA DSB response or DNA end-joining proteins on maintenance of genomic stability.
References: For a complete listing of publications on PubMed, click here.