I received my undergraduate degree in Chemistry from Brown University. As a student in the Medical Scientist Training Program at the Columbia University College of Physicians and Surgeons, I pursued my Ph.D. thesis research in the area of cytokine signal transduction under the mentorship of Dr. Paul Rothman. I received my M.D. and Ph.D. degrees in 2002, and went on to clinical Internal Medicine residency and subsequent clinical Hematology and Oncology fellowship at the University of Pennsylvania. As a fellow, I completed postdoctoral research training in the laboratory of Dr. Steven Reiner, where I studied the regulation of gene expression and cell fate decisions in T cells during immune responses. In 2010, I joined the faculty of the University of Maryland School of Medicine and started my own lab.
My laboratory team is interested in the molecular mechanisms governing gene expression patterns and differentiation in T lymphocytes both in the setting of anti-cancer immune responses and in the setting of T cell leukemia and lymphoma. We anticipate that our studies of T cells in these two different contexts, described in more detail below, will be complementary with our knowledge of non-malignant and malignant T cell biology each informing our research on the other.
T cell differentiation in anti-cancer immune responses. By the time a cancer reaches clinical significance, it has escaped the control of the immune system. The mechanisms by which T cells lose their anti-cancer activity remain incompletely defined. Antibodies directed against surface molecules including CTLA4, PD-1, and 4-1BB have all been shown to induce clinically significant T cell responses, however the inability to maintain a highly active and durable anti-cancer response remains a barrier to longstanding clinical success. We believe that mechanistic insights into the loss of activity in T cells within tumors, and into the induction of anti-cancer activity with current approaches will guide the design of novel immuno-therapeutic strategies.
Our goal in this project is to define the molecular mechanisms that influence T cell differentiation during both effective and ineffective anti-cancer immune responses. Our experiments are focused on the activities of two partially homologous transcription factors that are both members of the T-box gene family, T-bet and Eomesodermin (Eomes). While both factors are important in generating cell-mediated immune responses, we have recently described their opposing roles in effector versus memory differentiation. While T-bet stimulates terminal effector differentiation, Eomes supports long-term persistence as memory. We are currently determining the contributions of these transcriptional regulators to T cell fate in anti-cancer immunity.
Identification of novel therapeutic targets in T cell malignancies. T cell malignancies are notable for their poor prognosis with a lack of consensus on optimal management. In a second project, we are determining whether T-bet and Eomes, as regulators of differentiation in T cells, play a role in the biology of T cell leukemias and lymphomas. We have also initiated a project to identify mutations in all exons (exome) in peripheral T cell lymphoma (PTCL) and to conduct functional molecular studies to determine the contributions of specific mutations to PTCL biology.