Institute of Cellular Medicine

Staff Profile

Dr Shoba Amarnath

Newcastle University Research Fellow

Background

Background

I obtained a B.Sc. in Biochemistry from University of Madras, Chennai, India. I then moved to the University of Hull to pursue a M.Sc in Biotechnology and Molecular Biology. I stayed on in Hull on an Overseas Research Scholarship (ORS) award to continue my PhD with Prof. John Greenman. In 2005, I moved to the National Institute of Dental and Craniofacial Institute at the National Institutes of Health, to pursue a post-doctoral fellowship with Dr.Wanjun Chen. In 2007, I joined Dr.Daniel H. Fowler's laboratory at the Experimental Transplantation Immunology Branch, NCI, NIH. During my time at the NIH, the main focus of my research has been understanding the basic biology of regulatory T cells and the various signalling networks that maintain regulatory T cell function. My research at NIH has led to two clinical trials, patents, FOCIS awards etc. 

At Newcastle University, I have forged collaborations with Prof. Nick Reyolds, Prof. Penny Lovat and Prof. Mark Birch-Machin, which has resulted in numerous fundamental discoveries in cutaneous immunology. Our research on immune tolerance has identified key regulatory networks that maintain Treg cells and ILCs within melanoma and cutaneous inflammation. Ongoing work within the laboratory is further extending these fundamental studies in melanoma patients and atopic dermatitis.


Qualifications

2000- B.Sc. Biochemistry, Madras University, Tamil Nadu, India

2001- M.Sc. Biotechnology & Molecular Biology, University of Hull, Hull, UK

2005- Ph.D Immunology, University of Hull, Hull, UK


Previous Positions

2015-Present: Newcastle University Research Fellowship, Newcastle University

2011-2015: Research Assistant Professor, NCI, NIH, USA

2007-2011: Post-doctoral Fellow, NCI, NIH, USA

2005-2007: Visiting Post-doctoral Fellow, NIDCR, NIH, USA


Active collaborators include

Dr. Ethan Shevach, NIAID, NIH, USA

Dr. Sander van-kasteren, Leiden University

Prof. Colin Watts, Dundee University

Prof. Ruth Plummer, Newcastle University

Prof. Penny Lovat, Newcastle University

Prof. Nick Reynolds, Newcastle University

Prof. Mark Birch-Machin, Newcastle University


Funding

1. MRC DTP-DiMEN PhD Studentship

2. Springboard Award from the Academy of Medical Sciences 

3. Lonza

4. Wellcome


For any lab related resources/protocols please visit our laboratory website at

https://blogs.ncl.ac.uk/amarnath



Research


The research vision of my laboratory is to decipher the intricate immunological networks that regulate immune tolerance in health and disease. Specifically, we aim to identify proteins that control Treg cell function in inflammation and cancer. We are interested in developing a comprehensive analysis of the proteomic landscape within Tregs and test the function of each protein in invivo models of melanoma and cutaneous inflammation.


Our science requires skilled tools currently available within my lab: including animal models of cancer, autoimmunity, alloimmunity and humanised murine models of inflammation, along with protein and protease biochemistry methods. These tools have already proved their value and has helped identify a new protease in Tregs known as asparaginyl endopeptidase (AEP; lgmn) that can regulate Tregs (Stathopoulou, Mallet and Amarnath, Immunity, 2018) in cancer.


Our work on cutaneous inflammation has identified the expression of a well know T cell receptor called programmed cell death-1 (PD-1) on a new type of immune cell called Innate Lymphoid Cells (ILC-2s). This work was recently published by us (Taylor, Mallet, Stathopoulou, Amarnath, J.Exp.Med, 2017). In collaboration with Prof. Nick Reynolds, ongoing research within the laboratory involves deciphering the function of this population on immune cells within patient skin in atopic dermatitis.


Another area of research that has risen from our new technologies is the identification of metabolic signatures of various T helper cell subsets within the skin. In this research, preliminary findings have suggested that PD-1 can alter T cell metabolism. Ongoing work with Prof. Birch-Machin's laboratory include fully understanding how the bioenergetic demands to T helper cells are modulated by co-receptors.


Teaching

I have mentored numerous undergraduate, medical students, clinical fellows at the NIH.

I also lecture on T cells and ILCs which is part of the curriculum for the M.Res Immunobiology Module 

So far the laboratory has trained 5 B.Sc students, 6 M.Res Students at Newcastle University

Currently, there are 5 PhD students working towards their thesis


Publications

  • Stathopoulou C, Gangaplara A, Mallett G, Flomerfelt FA, Liniany LP, Knight D, Samsel LA, Berlinguer Palmini R, Yim J, Felizardo TC, Eckhaus MA, Edgington-Mitchell L, Martinez-Fabregas J, Zhu J, Fowler DH, van Kastern SI, Laurence A, Bogyo M, Watts C, Shevach EM, Amarnath S. PD-1 inhibitory receptor down regulates asparaginyl endopeptidase and maintains Foxp3 transcription factor stability in induced regulatory T cells. Immunity 2018, 49(2), 247-263.e7.
  • Taylor S, Huang Y, Mallet G, Stathopoulou C, Felizardo TC, Sun MA, Martin EL, Zhu N, Woodward EL, Elias M, Scott J, Reynolds NJ, Paul WE, Fowler DH, Amarnath S. PD-1 regulates KLRG1+ group 2 innate lymphoid cells. Journal of Experimental Medicine 2017, 214(6), 1663.
  • Amarnath S, Laurence A, Zhu N, Cunha R, Eckhaus MA, Taylor J, Foley JE, Ghosh M, Felizardo TC, Fowler DH. Tbet is a critical modulator of FoxP3 expression in autoimmune graft versus host disease. Haematologica 2017, 102, 1446-1456.
  • Whitehall G, Amarnath S, Muranski P, Keyvanfar K, Battiwalla M, Barrett AJ, Chinnasamy D. Adenosine selectively depletes alloreactive T cells to prevent GVHD while conserving immunity to viruses and leukemia. Molecular Therapy 2016, 24(9), 1655-1664.
  • Amarnath S, Foley JE, Farthing DE, Gress RE, Laurence A, Eckhaus M, Metais JY, Rose J, Hakim FA, Felizardo T, Cheng AV, Robey PG, Stroncek DE, Sabatino M, Battiwalla M, Ito S, Fowler DH, Barrett AJ. Bone Marrow-Derived Mesenchymal Stromal Cells Harness Purinergenic Signaling to Tolerize Human Th1 Cells In Vivo. Stem Cells 2015, 33(4), 1200-1212.
  • Mitra S, Ring AM, Amarnath S, Spangler JB, Li P, Ju W, Fischer S, Oh J, Spolski R, Weiskopf K, Kohrt H, Foley JE, Rajagopalan S, Long EO, Fowler DH, Waldmann TA, Garcia KC, Leonard WJ. Interleukin-2 Activity Can Be Fine Tuned with Engineered Receptor Signaling Clamps. Immunity 2015, 42(5), 826-838.
  • Fowler BJ, Gelfand BD, Kim Y, Kerur N, Tarallo V, Hirano Y, Amarnath S, Fowler DH, Radwan M, Young MT, Pittman K, Kubes P, Agarwal HK, Parang KA, Hinton DR, Bastos-Carvalho A, Li S, Yasuma T, Mizutani T, Yasuma R, Wright C, Ambati J. Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammaotry activity. Science 2014, 346(6212), 1000-1003.
  • Amarnath S. c-rel in GVHD biology. European Journal Of Immunology 2013, Vol 43(9), 2255-2158.
  • Felizardo TC, Foley J, Steed K, Dropulic B, Amarnath S, Medin JA, Fowler DH. Harnessing autophagy for cell fate control gene therapy. Autophagy 2013, 9(7), 1069-1079.
  • Amarnath S, Barrett AJ. Mesenchymal stromal cells:heroes or non-combatants. Cytotherapy 2013, 15(3), 253-254.
  • Mangus CW, Massey PR, Fowler DH, Amarnath S. Rapamycin Resistant Murine Th9 Cells Have a Stable In Vivo Phenotype and Inhibit Graft-Versus-Host Reactivity. PLoS ONE 2013, 8(8), e72305.
  • Amarnath S, Fowler DH. Harnessing autophagy for adoptive T cell therapy. Immunotherapy 2012, Vol. 4(1), 1-4.
  • Vazquez N, Gliozzi M, Feng C, Amarnath S, Orenstein JM, Wahl SM. Modulation of innate host factors by Mycobacterium avium in human macrophages includes IL17. Journal Of Infectious Diseases 2012, Vol. 206(8), 1206-1217.
  • Laurence A, Amarnath S, Mariotti J, Kim YC, Foley JE, Eckhaus M, OShea JJ, Fowler DH. STAT3 Transcription Factor Promotes Instability of nTreg Cells and Limits Generation of iTreg Cells during Acute Murine Graft-versus-Host Disease. Immunity 2012, 37(2), 209-222.
  • Miller TW, Wang EA, Gould S, Stein EV, Kaur S, Lim L, Amarnath S, Fowler DH, Roberts DD. Hydrogen sulfide is an endogenous potentiator of T cell activation. Journal of Biologocial Chemistry 2011, Vol. 287(6), 4211-4221.
  • Amarnath S, Mangus CW, Wang JCM, Wei F, He A, Kapoor V, Foley JE, Massey PR, Felizardo T, Riley JL, Levine BL, June CH, Medin J, Fowler DH. The PDL1-PD1 Axis Converts Human Th1 Cells Into Regulatory T Cells.. Science Translational Medicine 2011, Vol. 3(111), 111ra120.
  • Mariotti J, Taylor J, Massey PR, Ryan K, Foley J, Buxhoeveden N, Felizardo T, Amarnath S, Mossoba ME, Fowler DH. The Pentostatin Plus Cyclophosphamide (PC) Non-myeloablative Regimen Induces Durable Host T Cell Functional Deficits and Prevents Murine Marrow Allograft Rejection. Biology of Blood and Marrow Transplantation 2011, Vol.17(5), 620-631.
  • Amarnath S, Chen H, Foley JE, Costanzo CM, Solomon MA, Sennesh JD, Fowler DH. Host-Based Th2 Cell Therapy for Prolongation of Cardiac Allograft Viability. PLoS ONE 2011, 6(4), e18885.
  • Amarnath S, Flomerfelt F, Costanzo CM, Foley JE, Mariotti J, Konecki D, Gangopadhyay A, Eckhaus M, Levine BL, June CH, Fowler DH. Rapamycin Generates Anti-Apoptotic Human Th1/Tc1 Cells Via Autophagy for Induction of Xenogeneic GVHD. Autophagy 2010, 6(4).
  • Amarnath S, Costanzo CM, Mariotti J, Ullman J, Telford W, Riley JL, Levine BL, June CH, Fong T, Warner NL, Fowler DH. Regulatory T Cell Engineered Human Myeloid Dendritic Cells Prevent Xenogeneic GVHD Via Programmed Death Ligand-1. Plos Biology 2010, Vol. 8(2), e1000302.
  • Mariotti J, Foley J, Buxhoeveden N, Ryan K, Kapoor V, Amarnath S, Fowler DH. Graft rejection as a type I response amenable to modulation by type II donor T cells via an “infectious” mechanism. Blood 2008, Vol.112(12), 4765-4775.
  • AlHamarneh O, Amarnath S, Stafford N, Greenman J. Regulatory T-cells: What role do they play in anti-tumour immunity in patients with Head and Neck cancer?. Head and Neck 2008, Vol 30(2), 251-261.
  • Amarnath S, Li D, Liu YZ, Wu Y, Chen W. TGF-b is associated with induction of Foxp3 and regulation of HIV replication in TCR activated human CD4+CD25- T cells. Retrovirology 2007, Vol. 9(4), 57.
  • Rao SR, Amarnath S, Molinolo A, Hall B, Goldsmith CM, Zheng C, Larsson J, Sreenath T, Chen W, Karlsson S, Baum B, Kulkarni A. Female mice are more susceptible to developing inflammatory disorders due to impaired TGF-b signaling in salivary glands. Arthritis and Rheumatism 2007, Vol 56(6), 1798-1805.
  • Liu YZ, Amarnath S, Chen W. Requirement of CD28 signaling in homeostasis/survival of TGF-beta converted CD4+CD25+ Treg from thymic CD4+CD25- single positive T cells. Transplantation 2006, Vol. 82(7), 953-964.
  • Amarnath SMP, Dyer CE, Ramesh A, Iwaugwu O, Drew PJ, Greenman J. In vitro quantification of CD8+ CTL response against hTERT in breast cancer. International Journal of Oncology 2004, Vol 25(1), 211-217.