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Department
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Molecular Medicine
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Hospital Title
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Co-Chief, Division of Molecular Medicine
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Academic Title
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Charles A. Janeway Professor
of Pediatrics
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Phone
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617-919-2539
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Fax
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617-730-0948
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Email
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Frederick Alt
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Location
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300 Longwood Avenue
Karp-9
Boston MA 02115
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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 cis-acting chromosomal processes that effect accessibility. 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) repair 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 elucidation of the function of the mammalian SIRTuin (SIRT1-7) proteins in genomic stability, development, and aging. Standard laboratory approaches range from basic molecular genetics, biochemistry, cytogenetics, and genomics to gene-targeted mutation and the generation of novel animal-based approaches and models.
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Fred Alt received a PhD from the Department of Biological Sciences at Stanford University. He is a Howard Hughes Medical Institute investigator, a member of the National Academy of Sciences and the American Academy of Sciences. He is the recipient of He is the recipient of the 2003 Excellence in Mentoring Award from the American Association of Immunologists and the 2004 Clowes Memorial Award from the American Association of Cancer Research.
Honors and Awards
1973 Stephen J. Fox Memorial Award in Biological Sciences, Stanford University
1983 Irma T. Hirschl Career Scientist Award
1983 Searle Scholars Award
1984 Mallinckrodt Award
1991 NIH Merit Award
1994 Elected Fellow of the American Academy of Arts and Sciences
1994 Elected to the National Academy of Sciences
1994 Elected Fellow of the American Academy of Microbiologists
1999 Elected Foreign Member of the European Molecular Biology Organization
2003 American Association of Immunologists Excellence in Mentoring Award
2004 American Association of Cancer Research-G.H.A. Clowes Memorial Award
2005 Irvington Institute Scientific Leadership Award in Immunology
2005 Rabbi Shai Shacknai Memorial Prize in Immunology and Cancer Research
2005 Leukemia and Lymphoma Society de Villiers International Achievement Award
2005 Pasarow Foundation Prize for Extraordinary Achievement in Cancer Research
2005 Establishment of the Frederick W. Alt Award for New Discoveries in Immunology (a yearly award given to others by the Irvington Institute)
2007 Alfred Knudson Award for pioneering contributions that have revolutionized the field of Cancer Genetics from the National Cancer Institute
2007 American Association of Immunologists AAI-Huang Meritorious Career Award
2007 Novartis Prize for Basic Immunology
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- Basu, U., Chaudhuri, J., Alpert, C., Dutt, S., Rangananth, S., Li, G., Schrum, J.P., Manis, J.P. and Alt, F.W. (2005) The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation. Nature, 438, 508-511.
- Mostoslavsky, R., et al. (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell, 124, 315-329.
- Franco, S. Gostissa, M., Zha, S., Lombard, D.B., Murphy, M.M., Zarrin, A.A., Yan, C., Tepsuporn, S., Morales, J.C., Adams, M.M., Lou, Z., Bassing, C.H., Manis, J.P., Chen, J., Carpenter. P.B., and Alt, F.W. (2006) H2AX prevents DNA breaks from progressing to chromosome breaks and translocations. Molecular Cell, 21, 201-214.
- Zarrin, A.A., Del Vecchio, C., Tseng, E., Gleason, M., Tian, M., and Alt, F.W. (2007) Antibody Class Switching Mediated by Yeast Endonuclease Generated DNA Breaks. Science 315, 377-381.
- Yan, C., Boboila, C., Souza, E.K., Franco, S., Hickernell, T.R., Murphy, M., Gumaste, S., Geyer, M., Zarrin, A., Manis, J.P., Rajewsky, K., and Alt, F.W. (2007) IgH class switching and translocations use a robust non-classical end-joining pathway Nature. 449, 478-482.
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