Shoba M. Amarnath, Ph.D.
Dr. Amarnath's major research interest is to understand the mechanism by which human regulatory T cells inhibit xenogeneic graft-versus-host disease (x-GVHD).
Center for Cancer Research
National Cancer Institute
Building 10 - Hatfield Clinical Research Center, Room 3-3224
Bethesda, MD 20892-1203
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 (x-GVHD). My initial studies 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 x-GVHD lethality in murine models. These data suggest that blocking the PD1-PDL1 pathway would be beneficial for tumor therapy in humans. Studies are ongoing to better understand the expression and function of PDL1 in human Treg cells.
Currently, I am also 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.
Selected Recent Publications
- Eur. J. Immunol. 43: 2255-8, 2013. [ Journal Article ]
- Autophagy. 9: 1069-79, 2013. [ Journal Article ]
- Cytotherapy. 15: 253-4, 2013. [ Journal Article ]
Rapamycin resistant murine th9 cells have a stable in vivo phenotype and inhibit graft-versus-host reactivity.PLoS ONE. 8: e72305, 2013. [ Journal Article ]
- Autophagy. 8: 445-544, 2012. [ Journal Article ]
Dr. Amarnath completed her undergraduate degree in biochemistry from the University of Madras, Chennai, India. She also has a Master's degree in biotechnology and molecular biology from the University of Hull, UK. Dr. Amarnath was the recipient of the prestigious Overseas Research Scholarship Award, presented by the United Kingdom's Secretary of State for Education, to pursue a Ph.D. in immunology at the University of Hull. Upon completion of her Ph.D., Dr. Amarnath joined the Mucosal Immunology Section, under Dr.Wanjun Chen, at the National Institute of Dental and Craniofacial Research (NIDCR), to pursue a postdoctoral fellowship to study TGF-beta signaling in T-regulatory cells. She also conducted postdoctoral research at NCI in Dr. Daniel H. Fowler's laboratory, studying the mechanism of action of human regulatory T cells and T helper subsets in a novel human into mouse model of xenogeneic graft-versus-host disease (x-GVHD).