Michelle Gleason

E-mail: glea0038@umn.edu

Year entered: 2007

Thesis Advisor: Jeff Miller

Degree received:
B.S., Genetics, Cell Biology and Development, University of Minnesota, 2003

Honors and Awards:

• Graduate School Block Fellowship, Fall Semester 2007

Thesis research:

Natural killer (NK) cells are large granular lymphocytes with natural cytotoxicity against virally infected and tumor cells. NK cell activity is regulated by a variety of cell surface activating and inhibitory receptors. The integration of antagonist signals upon receptor-ligand interactions mediates the dynamic equilibrium that governs NK cell function and determines whether or not NK cells will eliminate the encountered targets. A novel receptor, Tim-3, is present on a variety cells, including a subset of T cells, and preliminary data by our lab shows its presence on human NK cells. The only ligand of Tim-3 identified thus far is galectin-9 (Gal-9), a beta-galactoside binding lectin, which is expressed on cells in a wide range of tissues, with highest expression in the bone marrow. Tim-3/Gal-9 interactions result in differential signaling depending on the cell type, with an inhibitory effect on T helper 1 cells and an activating effect on T regulatory and dendritic cells. However, the role of Tim-3/Gal-9 interaction has yet to be described in the context of human NK cell biology. The first aim of my project involves investigating the role the Tim-3/Gal-9 pathway plays in mediating NK cell function. Our preliminary data suggest Tim-3 acts to positively regulate NK cell effector function as Tim-3+ NK cells demonstrate significant increases in killing and cytokine secretion against Gal-9 expressing targets. The second aim of my project will examine the role of Tim-3 in NK cell development. Our preliminary data show the expression of Tim-3 in early developing NK cells. As NK cells develop in the bone marrow where Gal-9 expression is high, it is possible the Tim-3/Gal-9 interaction may influence NK cell development. Therefore, I am setting up a culture model utilizing CD34+ UCB progenitor cells and the murine embryonic liver stromal cell line EL08-1D2 with and without Gal-9 expression and examining the effects of the Tim-3/Gal-9 interaction on the different stages of NK cell development.