Mandy Ford Receives Renewal of R01 to Increase Understanding of Transplantation Intolerance
In 2008, Mandy Ford, PhD, current scientific director of the Emory Transplant Center (ETC), assisted Christian Larsen, MD, DPhil, then director of the ETC, in the writing of a grant proposal that resulted in an NIH R01 for investigating determinants of T-cell fate in transplant tolerance. The prior year, Ford had completed her postdoctoral fellowship in Larsen's transplant immunology lab.
In 2009, Ford became the principal investigator of the grant, and dug deeper into identifying new pathways that control memory T-cell responses during transplantation. T-cells are a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated immunity, and are considered a primary mediator of the rejection of transplanted organs.
Ford and her team discovered that FcyRIIB, a protein previously known to be responsible for "turning off" B cells, another lymphocyte responsible for producing antibodies, was also produced by a subset of memory T cells in mice after transplant. Preliminary data additionally suggested that those T cells with an excess of the FcγRIIB inhibitor were more susceptible to belatacept, the immunotherapeutic agent developed and tested in large part by Larsen and his team here at Emory.
Armed with this discovery, Ford applied for and recently received her first R01 renewal from the NIH as principal investigator. The grant, entitled "Determinants of T Cell Fate in Transplantation Tolerance," will allow further investigation of this new pathway.
"We are excited about the possibility that this molecule has the potential to control memory T cell responses in transplantation," says Ford. "With this grant, we will explore the mechanisms of how FcγRIIB works, what molecule or molecules trigger it, how we can increase expression of this inhibitory pathway on memory T cells, and how we can then target it therapeutically to better control rejection."