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

Four Boston research institutions, under the leadership of The Immune Disease Institute, have received a $6.25 million grant from the Leukemia and Lymphoma Society, to develop potential new therapies for B-cell lymphomas. The SCOR (Specialized Center for Research) grant is directed by IDI Senior Investigator Fred Alt, with IDI Senior Investigator Klaus Rajewsky as co-director of two projects within the grant.

The Leukemia and Lymphoma Society is the world's largest voluntary health organization dedicated to funding blood cancer research, education, and patient services.

The Immune Disease Institute, together with the Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Children's Hospital Boston, will run this grant, which is entirely focused on B-cell lymphomas -- cancers originating in the lymphatic system. These cancers result when a lymphocyte (a type of white blood cell) undergoes a malignant change and multiplies, crowding out healthy cells and creating tumors. Nearly 70,000 Americans develop lymphoma each year.

The grant recipients will focus their research on two properties of malignant B-cells: oncogenic B-cell receptor (BCR) signaling and DNA repair-associated genetic abnormalities. Five simultaneous projects will research these two fundamental properties.

The grant will bring together several scientists, who have experience in mouse modeling, human pathology, protein biochemistry, and immunology, with the goal of identifying predisposing factors and improving lymphoma therapies. The incidence of the most common human B-cell lymphoma has doubled over the past generation and the majority of these diseases still remain incurable.

Project 1, led by Dr. Alt, Ph.D., of IDI, will focus on how DNA double-strand break response pathways suppress oncogenic translocations in novel mouse B lymphoma models, and will assess how often abnormalities in these pathways occur in human lymphomas.

Project 2, led by Glenn Dranoff, M.D., of the Dana-Farber Cancer Institute (DFCI), will use DNA repair mouse models and primary human lymphomas to show how DNA damage inhibits an effective host anti-tumor response. The ultimate goal is to reverse this process.

Project 3, led by Margaret Shipp, M.D., of DFCI and Klaus Rajewsky, M.D., of IDI will use both in vitro and in vivo models of perturbed protein tyrosine phosphantase function and proximal SRC-related kinase activity to address the broader role of BCR-mediated survival signals in large B-cell lymphomas.

Project 4, led by Loren D. Walensky, M.D., of DFCI and Klaus Rajewsky, M.D., of IDI, will attempt to inhibit oncogenic BCR signaling at multiple control points using chemically reinforced, peptidic compounds.

Project 5, led by Anthony G. Letai, M.D., of DFCI, will target downstream survival pathways by defining the efficacy and mechanisms of action of newly developed BCL-2 family inhibitors.

Project Co-leader Klaus Rajewsky, M.D., of the Immune Disease Institute says, "This grant will give us all the opportunity to research aspects of lymphoma that we otherwise would have been unable to attack. It is very exciting and a great opportunity to make strides in therapies for lymphoma."

The money will be awarded over a five-year period beginning October 1, 2006.