Assistant Professor, Eppley Institute
Tel: 402-559-5241 (Office),
Lymphoid Malignancies (B-cell leukemia and lymphoma)
Summary of Research
My research focuses on (i) understanding the pathogenesis of B-cell malignancies and (ii) evaluating novel targeted therapies for B-cell chronic lymphocytic leukemia (CLL) and Richter's transformation (RT) - an aggressive and incurable diffuse large B-cell lymphoma (DLBCL) that arises in the setting of CLL- with the overall aim of translating effective therapies to the clinic. Specifically, my laboratory aims to explore the dynamic cross-talk between malignant B-CLL cells and their microenvironment through a wide array of cell-based assays to identify "druggable" targets and pathways for therapeutic intervention which will be further evaluated utilizing the available mouse models of aggressive CLL/RT disease.
Current studies in the laboratory are focused on epigenetic-based therapies including novel small molecule inhibitors of the bromodomain and extra-terminal (BET) family proteins, and their ability to modulate TME interplay in CLL. This is based on recent studies on the BET family protein “BRD4” which validated BRD4 inhibition as an epigenetic approach capable of downregulating multiple survival pathways in CLL. Importantly, these BRD4 profiling studies in CLL patient-derived tumor B-cells identified previously unrecognized targets of BRD4 implicated in CLL disease biology, progression and CLL-TME interactions including various chemokine/cytokine receptors and immune regulatory checkpoint molecules, indicating unique BRD4-mediated immunomodulatory properties which have yet to be fully investigated. Therefore, a major project in the laboratory aims to (1) investigate the immunomodulatory effects of BRD4 inhibition using in vitro approaches mimicking CLL-TME interplay; (2) study the ability of BRD4 inhibition to reverse immune dysfunction inherent to CLL; and (3) evaluate BRD4 inhibition in mouse models of aggressive CLL/RT, and its ability to reprogram the TME to disrupt protective niches and/or correct the immune defects commonly observed in this disease.