Contact: Alexander Shtifman
Phone: 617-713-8989
alex...@childrens.harvard.edu

The 44th Rosenstiel Award for Distinguished Work in Biomedical Science has been awarded to Dr. Frederick W. Alt, the Director of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital. He is also Charles A. Janeway Professor of Pediatrics and Professor of Genetics, Harvard Medical School and Investigator of the Howard Hughes Medical Institute. Dr. Alt is honored for his pioneering work in elucidating the mechanisms of genome rearrangements in immune and cancer cells.


Fred Alt’s fascination with changes in gene arrangement and expression began in graduate school with his demonstration of the selective amplification of the DHFR gene in cancer cells resistant to therapy with methotrexate, studies which also provided the first molecular demonstration of genomic instability in cancer.  Several years later, in his own lab, Alt showed selective amplification of the N-myc oncogene in neuroblastomas.  The finding of a novel cancer-related gene, recurrently amplified in a specific type of human tumor, at a particular stage, was a landmark in showing that gene amplification is a fundamental mechanism underlying tumorigenesis.  Much of Fred Alt’s work has focused on a set of programmed chromosomal rearrangements that occur during the development of the immune system.  Alt’s lab has provided many of the insights into the mechanisms by which particular immune gene regions are activated for rearrangement in both B and T lymphocytes. His lab was the first to show that immune cell rearrangements depended on genes directing general repair of chromosome breaks and subsequently identified new factors and processes by which broken DNA segments are joined together.  Alt’s focus on the mechanisms of joining distant broken DNA segments has continued with his more recent work on the origin of chromosomal translocations. One major discovery, linking Alt’s earlier work on gene amplification with his study of the immune system, was the mechanism of oncogenic gene amplifications in repair-defective progenitor B lymphocytes that lead to lymphomas.  By using new genome-wide DNA sequencing methodology his lab has described the spectrum of rearrangements arising between a specifically broken genomic segment and many other sites in the genome where breakage arises spontaneously or after irradiation. His work continues to unveil the complex mechanisms of chromosomal maintenance and the consequences of their inactivation.

The Rosenstiel Award, founded in 1972, has had a distinguished record of identifying and honoring pioneering scientists who subsequently have been honored with the Lasker and Nobel Prizes.  Last year Brandeis honored Drs. Watt Webb, Wilfried Denk and David Tank for their development of two-photon imaging of neural circuits.  The previous year cited Stephen Elledge for his insights concerning the way cells respond to DNA damage.  Recent previous winners include Nahum Sonenberg for his work in the regulation of protein translation; David Allis and Michael Grunstein for demonstrating the role of histone modifications in the regulation of gene expression; Jules Hoffman and Ruslan Medzhitov for their discoveries in innate immunity; John Gurdon, Shinya Yamanaka and Irving Weissman for the development of pluripotent stem cells; Arthur Horwich and F. Ulrich Hartl for their work in protein folding; and Mary Lyon, Davor Solter and Azim Surani for their studies of epigenetic programming in embryos.  A full list of awardees can be found at http://www.rose.brandeis.edu/Center/rose_past.html