Immune Disease Institute

Frederick Alt and his colleagues study the molecular mechanisms involved in the somatic assembly and modification of antigen receptor genes in B and T lymphocytes.  They also study general mechanisms that suppress genomic instability and cancers of the immune system.  Laboratory approaches range from basic molecular genetics, cell biology and biochemistry to state of the art confocal imaging, gene-targeted mutation and novel animal-based approaches and models.  One set of Alt lab studies seeks to elucidate mechanistic and regulatory aspects of antigen receptor variable region gene assembly (V(D)J recombination) in developing B and T lymphocytes and immunoglobulin heavy chain class switch recombination (CSR) and somatic hypermutation in activated mature B lymphocytes.  Another major set of Alt lab studies seeks to elucidate mechanisms that function to suppress genomic instability and cancer, with a focus on elucidation of the function of the DNA double strand break (DSB) response and the non-homologous end joining (NHEJ) pathway of DSB repair.  In recent years, these two lines of research have frequently intersected in the context of elucidating the roles of NHEJ and DSB response proteins in V(D)J recombination and CSR and suppression of oncogenic translocations associated with aberrancies in these lymphocyte-specific recombination processes.  One major ongoing effort involves the elucidation of mechanistic and selective factors that contribute to recurrent translocations and gene amplifications found in various types of B and T lymphomas and in solid tumors.

Dr. Alt received his Ph.D. in Biology from Stanford University in 1977 with Robert Schimke and he did his postdoctoral work at MIT with David Baltimore.  He was a Professor at Columbia University from 1982-1991, where he became an HHMI Investigator in 1987.  In 1991, Dr. Alt moved to Harvard Medical School as a Professor of Genetics and Pediatrics, an HHMI Investigator at Boston Children's Hospital and a Senior Investigator at the Immune Disease Institute.  He was appointed Charles A. Janeway Professor of Pediatrics in 1993 and Scientific Director of the Immune Disease Institute in 2005.  Dr. Alt has been elected to the U.S. National Academy of Sciences, the American Academy of Arts and Sciences, the American Academy of Microbiology, and the European Molecular Biology Organization.  He has received the Clowes Memorial Award from the American Association of Cancer Research; the Rabbi Shai Shacknai Prize from The Hebrew University, the Pasarow Foundation Prize for Extraordinary Achievement in Cancer Research, the Leukemia & Lymphoma Society de Villiers International Achievement Award, the Irvington Institute Immunology Award, the National Cancer Institute Alfred K. Knudson Award for pioneering contributions that have revolutionized the field of Cancer Genetics, the American Association of Immunologists AAI-Huang Meritorious Career Award, and the Novartis Basic Immunology Prize for his discoveries on B cell development and antigen responses.  Dr. Alt has mentored over 100 students and research fellows, many of whom have become leaders in immunology, genetics, or cancer biology and has received the American Association of Immunologists Excellence in Mentoring Award.  The Cancer Research Institute (New York) annually presents the Frederick W. Alt Award for New Discoveries in Immunology.