Postdoctoral Fellowship with Robert S. Negrin


Regulation of graft-versus-host disease (GVHD) by NKT cells.  Discovered that NKT cells can potently regulate GVHD at very low numbers.  Further elucidated that mechanism of action involved IL-4 production by NKT cells and resulted in a decrease of Th1-type cytokines by conventional T cells.  Also elucidated the migration and proliferation of NKT cells in a transplantation setting and examined their anti-tumor activity and their effect on the anti-tumor activity of conventional T cells.  This work was recently published in Blood.


Mast cell suppression of GVHD.  Discovered the surprising finding that during GVHD induction, the presence of Mast cells results in reduced proliferation of allogeneic T cells and less GVHD.  Furthermore, engraftment of bone marrow-derived cultured Mast cells into Mast cell knockout mice results in improved survival of the mice. Also, we did not find any involvement of Mast cells in Treg-mediated suppression of GVHD.  This work received an oral presentation and travel award at the 2010 annual meeting of the American Society of Hematology (ASH), and a manuscript is in preparation. 


Induction of tolerance to embryonic and induced Pluripotent stem cells.   In collaboration with the Wu lab, investigated mechanisms by which a co-stimulatory blockade of T cell activation could induce tolerance to stem cells.  This work will appear in the March, 2011 issue of Cell Stem Cell.   This project is ongoing with the current focus being on CD4+CD25+ regulatory T cell-mediated promotion of engraftment of embryonic stem cells.


NK cell regulation of GVHD.  Discovered that NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects.  Determined that the addition NK cells into a model of acute GVHD results in less proliferation of T cells and decreased interferon-gamma production.  Furthermore, NK cells caused direct lysis of T cells in vitro.  Fortunately, the graft-versus-tumor effect was retained in the presence of NK cells.  This work resulted in a publication in Blood.


Determination of the differential effects of IL-18 and rapamycin on CD4+CD25+ regulatory T cells (Tregs).  Discovered that IL-18 and rapamycin have differential effects of Treg versus conventional T cells which could be exploited to treat GVHD.  The IL-18 work was published in Biology of Blood and Marrow TransplantationThe rapamycin work was published in Blood