Professor of Biology
A.B., Bryn Mawr College
VMD, PhD University of Pennsylvania
My undergraduates and I are interested in how cells make decisions and have focused on the process of negative selection, an event that helps rid our immune system of autoreactive cells (in our case, T lymphocytes). Specifically, we want to understand why immature T cells die in response to T cell receptor signals and their mature descendants not only survive but divide in response to the same signal. This difference in cell fate underlies our ability to fend off infection without destroying our own cells.
This work led us to a specific interest in the protein Nur77, which was rapidly expressed by both immature and mature T cells in response to T cell receptor signals. In order to better understand the role of this protein in t cell development and responses we generated a mouse whose cells fluoresced green whenever they expressed Nur77. In collaboration with colleagues at the University of Minnesota we showed that the levels o Nur77 expression vary directly with the strength of T cell receptor signaling. This 'reporter' mouse is helping us better understand the relationship between the fate of a T cell and the signals it experienced during its development.
This mouse also inspired our interest in decisions made by other blood cells that, unexpectedly, expressed Nur77 (and 'glowed green' in our mouse). These include a unique monocyte population that appears to quiet rather than inspire an immune response, and a subpopulation of hematopoietic stem cells. This latter finding inspired a collaboration with hematologist and stem cell biologist Steve Emerson and led us to speculate that a common view that Nur77 is pro-apoptotic is too simplistic. Rather, it may regulate cell cycle and/or metabolic status of a cell - allowing it to 'pause' before making a fate decision (death, survival, division or differentiation).
Undergraduates have inspired every step in this process - their imaginations and energies are enviably unfettered.
Courses: Spring 2013, Haverford