Last week the American Society of Hematology announced recipients for its 2015 awards. Dr. Wendy Beguelin a postdoctoral scientist at WCMC, under the supervision and mentorship of Dr. Ari Melnick received a Basic Research Fellows award for her work in lymphoma epigenetics. Recipients receive $100,000 over a two to three year period to support basic translational and clinical research that advances the hematology field.
In her work Dr. Beguelin identified novel epigenetic and transcriptional mechanisms that contribute to B-cell differentiation and lymphomagenesis. She revealed the role of the Polycomb protein EZH2 in humoral immunity and the mechanism through which somatic gain of function EZH2 mutations occurring in human lymphoma patients reprograms the epigenome to mediate malignant transformation. Her group introduced the novel concept of “bivalent gene targeted therapy”, by showing that mutant EZH2 freezes bivalent domains (genes featuring overlapping repressive and activation histone marks) in a locked silenced configuration that can be reversed to great therapeutic effect using specific EZH2 inhibitors. This led to the identification of biomarkers indicating the subset of human lymphoma patients amenable to EZH2 inhibitor therapy. This new information was used to design the first in vivo clinical trial of the first GSK EZH2 specific inhibitor that is currently underway at our institution.