Ashley Sandy
e-mail address: asandy@umich.edu

Mentor: Ivan Maillard, MD, PhD

Research Description

Notch signaling is a highly conserved cell-to-cell communication system. Notch receptors (Notch 1-4) bind to Notch ligands of the Delta-like or Jagged family, leading to a series of proteolytic cleavage steps that release intracellular Notch and to downstream target gene activation. Besides its important role at early stages of T cell development, Notch emerges as a potent context-specific regulator of T cell differentiation and function. We are investigating the role of Notch signaling in allogeneic T cell responses against foreign tissue antigens. We found that targeted inactivation of Notch signaling in mature T cells resulted in greatly improved survival in murine models of graft-versus-host disease (GVHD) and immune-mediated aplastic anemia. The goal of my research is to understand the mechanisms by which Notch signaling potentiates alloreactive T cell responses, and conversely, to determine how inactivation of Notch signaling protects against tissue damage induced by alloreactive T cells. To this effect, I plan to identify novel transcriptional targets regulated by Notch in mature T cells as well as potential crosstalk between Notch signaling and other pathways that control T cell activation and differentiation.

Publications

Vomhof-DeKrey, E. E., Hermann, R. J., Palmer, M. F., Benton, K., Sandy, A. R., Dorsam, S., Dorsam, G. P., 2008.  TCR signaling and environment affect vasoactive intestinal peptide receptor-1 expression in primary mouse CD4 T cells.  Brain, Behav., Immun. 22(7):1032-40.

Abstracts

Awards

MAAS Deans Fellowship