Shoba M. Amarnath, Ph.D.
Shoba M. Amarnath, Ph.D.
Staff Scientist

Center for Cancer Research
National Cancer Institute

Building 10 - Hatfield Clinical Research Center, Room 3-3224
Bethesda, MD 20892-1203
301-594-9687

Dr. Amarnath completed her undergraduate degree in Biochemistry from the University of Madras, Chennai, India. She also has a Masters 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 UK state government to pursue a PhD in Immunology at the University of Hull, UK. Upon completion of her PhD, Dr. Amarnath joined the Mucosal Immunology Section under Dr.Wanjun Chen at NIDCR to pursue a post-doctoral fellowship to study TGF-beta signaling in T-regulatory cells. She also conducted post-doctoral research at NCI in Dr. Daniel H Fowler 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).

Areas of Expertise
T cells

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.

Selected Publications
  1. Mangus CW, Massey PR, Fowler DH, Amarnath S.
    PLoS ONE. 8: e72305, 2013. [ Journal Article ]
  2. Klionsky et al DJ.
    Autophagy. 8: 445-544, 2012. [ Journal Article ]
  3. Peer CJ, Rao M, Spencer SD, Shahbazi S, Steeg PS, Schrump DS, Figg WD.
    J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.. 927: 142-6, 2013. [ Journal Article ]
  4. Portal-Nuñez S, Shankavaram UT, Rao M, Datrice N, Atay S, Aparicio M, Camphausen KA, Fernández-Salguero PM, Chang H, Lin P, Schrump DS, Garantziotis S, Cuttitta F, Zudaire E.
    Cancer Res.. 72: 5790-800, 2012. [ Journal Article ]
  5. Zhang M, Mathur A, Zhang Y, Xi S, Atay S, Hong JA, Datrice N, Upham T, Kemp CD, Ripley RT, Wiegand G, Avital I, Fetsch P, Mani H, Zlott D, Robey R, Bates SE, Li X, Rao M, Schrump DS.
    Cancer Res.. 72: 4178-92, 2012. [ Journal Article ]

Dr. Amarnath completed her undergraduate degree in Biochemistry from the University of Madras, Chennai, India. She also has a Masters 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 UK state government to pursue a PhD in Immunology at the University of Hull, UK. Upon completion of her PhD, Dr. Amarnath joined the Mucosal Immunology Section under Dr.Wanjun Chen at NIDCR to pursue a post-doctoral fellowship to study TGF-beta signaling in T-regulatory cells. She also conducted post-doctoral research at NCI in Dr. Daniel H Fowler 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).

Summary

Dr. Amarnath completed her undergraduate degree in Biochemistry from the University of Madras, Chennai, India. She also has a Masters 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 UK state government to pursue a PhD in Immunology at the University of Hull, UK. Upon completion of her PhD, Dr. Amarnath joined the Mucosal Immunology Section under Dr.Wanjun Chen at NIDCR to pursue a post-doctoral fellowship to study TGF-beta signaling in T-regulatory cells. She also conducted post-doctoral research at NCI in Dr. Daniel H Fowler 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).

Areas of Expertise
T cells

Research

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.

Publications

Selected Publications
  1. Mangus CW, Massey PR, Fowler DH, Amarnath S.
    PLoS ONE. 8: e72305, 2013. [ Journal Article ]
  2. Klionsky et al DJ.
    Autophagy. 8: 445-544, 2012. [ Journal Article ]
  3. Peer CJ, Rao M, Spencer SD, Shahbazi S, Steeg PS, Schrump DS, Figg WD.
    J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.. 927: 142-6, 2013. [ Journal Article ]
  4. Portal-Nuñez S, Shankavaram UT, Rao M, Datrice N, Atay S, Aparicio M, Camphausen KA, Fernández-Salguero PM, Chang H, Lin P, Schrump DS, Garantziotis S, Cuttitta F, Zudaire E.
    Cancer Res.. 72: 5790-800, 2012. [ Journal Article ]
  5. Zhang M, Mathur A, Zhang Y, Xi S, Atay S, Hong JA, Datrice N, Upham T, Kemp CD, Ripley RT, Wiegand G, Avital I, Fetsch P, Mani H, Zlott D, Robey R, Bates SE, Li X, Rao M, Schrump DS.
    Cancer Res.. 72: 4178-92, 2012. [ Journal Article ]

Biography

Dr. Amarnath completed her undergraduate degree in Biochemistry from the University of Madras, Chennai, India. She also has a Masters 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 UK state government to pursue a PhD in Immunology at the University of Hull, UK. Upon completion of her PhD, Dr. Amarnath joined the Mucosal Immunology Section under Dr.Wanjun Chen at NIDCR to pursue a post-doctoral fellowship to study TGF-beta signaling in T-regulatory cells. She also conducted post-doctoral research at NCI in Dr. Daniel H Fowler 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).