Grant: Project Grant

Besides complex and heterogeneous DNA mutations, cancer cells harbor global alterations of the epigenetic landscape, which are associated with aberrant cell-fate programs. The dependency on altered chromatin states is thought to provide great therapeutic opportunities since epigenetic aberrations are reversible and dynamically controlled by enzymatic and biochemical activities that are amenable to drug modulation. Recently our laboratory identified the chromatin remodeling factor SMARCD1 as an essential gene for the proliferation and survival of B-cell non-Hodgkin lymphomas - the seventh most common neoplasm affecting adults in the United States. Our current work further identifies the E2A oncogene and p53 tumor suppressor as downstream mediators of SMARCD1 function in this disease. In this application, we will decipher the molecular mechanisms by which SMARCD1 impinge on these two frequently mutated pathways in B-cell lymphoma. This work will advance our understanding of the epigenetic mechanisms underlying lymphomagenesis and may eventually lead to better management of diseases involving B-cell dysfunction.