Highlights | 2015


November 12, 2015

Using passenger alleles to elucidate the targeting of AID in immunity

by Paul Guttry

Researchers in the laboratory of Frederick Alt at the Howard Hughes Medical Institute and Program in Cellular and Molecular Medicine (PCMM) at Boston Children's Hospital, led by Leng-Siew Yeap and Joyce K. Hwang, have fundamentally changed our understanding of how the crucial mutagenic activity of activation-induced cytidine deaminase (AID) is targeted during antibody maturation.

In an article published online in Cell on November 19, 2015, they demonstrate that the DNA sequence encoding the antigen-binding variable (V) region of B-cell antibodies lies in a genomic location privileged for mutational diversification by AID.  Their study further reveals that no specialized mechanism beyond sufficient exposure to AID is required to generate antibodies whose neutralizing function depends on high levels of variable-region mutations and deletions.

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 October 22, 2015

Genomic loops keep genes and enzymes on track and out of trouble

The looping organization of DNA may itself be a basic form of gene control

BOSTON, Oct. 22, 2015 /PRNewswire-USNewswire/ -- A study of where and how an enzyme cuts DNA may have inadvertently revealed a basic principle of gene regulation, say researchers in Boston Children's Hospital's Program in Cellular and Molecular Medicine (PCMM). The study, reported in the journal Cell, suggests that the cell can lock or "sandbox" genes and enzymes that act on them within loops of DNA and protein, confining their activity to minimize the risk of genetic disaster.

In our cells, DNA and its associated proteins—a combination called chromatin—are folded and wrapped in complex ways to form chromosomes. Researchers have long noted within a chromosome, the chromatin is organized into a series of loops. These loops can range in size from a few thousand to nearly 2.5 million base pairs, large enough to contain one or more complete genes.

The study team—led by co-first authors Jiazhi Hu, PhD, and Yu Zhang, PhD, and senior author Frederick Alt, PhD—believes these loops may form the backbone of a fundamental organizing principle for genomic processes.

 May 22, 2015

Dr. Frederick W. Alt  received the 2015 Katherine Berkan Judd Award from the Memorial Sloan Kettering Cancer Center.  

This award is given annually for Distinguished Achievement in Biomedical Research.   The Judd Award was established in 1936 by Mrs. Judd.   She had the foresight and vision to realize that, in the future, scientists would make great strides towards the control and understanding of cancer through basic discovery.   Toward that end, she provided that a portion of her estate be designated as the Katherine Berkan Judd Cancer Fund.  Dr. Alt was selected to receive the Judd award this year for his contributions to understanding DNA repair pathways the mediate recombination in the immune system, and the relevance of these pathways to chromosomal translocation and oncogenesis.

April 29, 2015

Frederick Alt honored with 2015 Szent-Györgyi Prize for Progress in Cancer Research

Frederick Alt, PhD, director of the Program in Cellular and Molecular Medicine at Boston Children's Hospital, has been honored with the 2015 Szent-Györgyi Prize for Progress in Cancer Research. Awarded by the National Foundation for Cancer Research (NFCR), the prize recognizes Alt's groundbreaking work on the genetic nature of cancer, research that laid the foundation for our modern understanding of cancer and for the current revolution in personalized, targeted cancer treatment.

The Keynote speech at the award ceremony was delivered by Edward Markey, United States Senator for Massachusetts 

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April 13, 2015

Congratulations to Fred Alt, Recipient of the 44th Rosenstiel Award for Distinguished Work in Biomedical Science

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.

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