Our Science – Amarnath Website
Shoba M. Amarnath, Ph.D.
Regulatory T cells (Treg) are a subset of T cells that are involved in maintaining tolerance thereby inhibiting optimal T cell function against various cancers. Understanding the mechanism of action of Tregs will result in the development of therapies that would be resistant to immune tolerance in cancer patients.
My major research interest is to understand the mechanism by which human regulatory T cells inhibit xenogeneic graft versus host disease. Initial studies conducted by me suggest that human Tregs suppress Th1 effectors predominantly through the molecule programmed death ligand 1 (PDL1). Blocking the PD1-PDL1 pathway in vitro and in vivo results in increased GVHD lethality in our murine models. These data suggest that blocking PD1-PDL1 pathway would be beneficial for tumor therapy in humans. Studies are ongoing in better understanding the expression and function of PDL1 in human Treg cells.
I am also currently studying the various mechanisms by which human Th1 cells can be polarized in the presence of the drug rapamycin. Our current understanding of this drug suggests that T cells when polarized in the presence of cytokines such as IL2, IFNa2b and rapamycin acquire a fixed Th1 polarity and cause lethal x-GVHD in mice. These Th1 cells become resistant to rapamycin mediated inhibition by undergoing a process called autophagy. This rapamycin resistant phenotype allows the cells to persist long term in mouse models of x-GVHD thereby making them a suitable candidate for tumor immunotherapy strategies.
This page was last updated on 3/21/2013.