Dr. Béguelin Presents Abstract at ASH Meeting: One of Six Papers Selected from Six Thousand

Dr.  wendybeguelin

Dr. Béguelin

Dr. Béguelin Presents Abstract at ASH Meeting: One of Six Papers Selected from Six Thousand It was more good news for the Melnick Lab, internationally recognized for its work on cancer and epigenetics, when Wendy Béguelin, Ph.D. learned that her project abstract had been selected for presentation at the plenary session of the 55th Annual Meeting of the American Society of Hematology (ASH) being held this weekend in New Orleans, LA. The President of ASH, Janis L. Abkowitz, M.D., informed Dr. Béguelin, who is a Revson Fellow working on lymphoma research, that her paper was one of only six chosen from more than 6,000 reviewed by the ASH Program Committee. A prestigious honor, Dr. Béguelin will report on her findings at the plenary session this Sunday, December 8. The attendees will include most of the more than 20,000 physicians and scientists expected to participate in the 2013 ASH Annual Meeting.

Building on the Melnick Lab's research identifying novel disease mechanisms and therapeutic targets in B-cell lymphomas, the 4th most common malignancy in the United States. Dr. Béguelin will present her recent discoveries outlining the mechanism of action of a protein called EZH2, which functions as a histone methyltransferase that silences gene expression. EZH2 was known as a crucial regulatory factor for stem cells, but was also found to be present within the immune system. In particular EZH2 is especially highly produced when B-type lymphocytes are activated to produce antibodies against invading microbes. It so happens that these activated B-lymphocytes are the same cells that give rise to almost all B-cell lymphomas.

“One of our key findings” explains Dr. Béguelin, ”is that EZH2 is required for B-lymphocytes to form so-called germinal centers. Germinal centers of peripheral lymphoid organs are the main sites where high affinity antibodies are generated during the immune response.” Dr. Béguelin and colleagues also revealed that EZH2 mediates germinal center formation by forming a specialized kind of chromatin that was previously thought to be uniquely associated with stem cells, but which in B-lymphocytes causes a different biological effect specifically enabling these cells to rapidly divide until they can form high-powered antibodies. Perhaps most crucially, Dr. Béguelin showed that EZH2 mutations known to occur in B-cell lymphomas actually convert EZH2 into a ”super-repressor” that permanently locks chromatin into a repressive state that causes lymphomas to arise from normal B-lymphocytes.

Her final and most crucial observation, which is the core of her presentation at the ASH plenary session, is that for this to happen, EZH2 must cooperate with another master regulatory factor called ”BCL6” which also serves as a gene repressor. It is only through their combined and coordinate actions that cancer-causing gene silencing can occur in malignant lymphomas. Fortunately, the Melnick Lab has previously been able to develop drugs that target BCL6. In her new research Dr. Béguelin shows that combinations of BCL6 and EZH2 inhibitors are highly synergistic in destroying lymphomas and thus represent an exciting new rationally designed treatment regimen for this disease. Dr. Béguelin obtained her Ph.D. in Biological Sciences from the School of Exact and Natural Sciences at the University of Buenos Aires, Argentina. After serving a fellowship sponsored by the National Council for Scientific and Technological Research (CONICET) in Argentina, she joined Weill Cornell in 2010 as a postdoctoral fellow in the Division of Hematology and Medical Oncology. In 2013, she received a two-year fellowship from the Charles H. Revson Foundation and is now serving as The Charles H. Revson Senior Fellow in Biomedical Science. She has published her work in some of the leading peer-reviewed journals, including Cancer Cell, Journal of Immunology, and Molecular and Cellular Biology. Read Paper.


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