Staff Profile
Dr Shoba Amarnath
Reader in Immune Regulation
- Email: shoba.amarnath@ncl.ac.uk
- Telephone: 01912085074
- Personal Website: https://blogs.ncl.ac.uk/amarnath/
- Address: Biosciences Institute
Cell Signalling
NUCancer
Room M4.179
4th floor William Leech Building
The Medical School
Framlington Place
Newcastle Upon Tyne
NE2 4HH
Tel: +44 (0) 1912088257
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. I joined Dr.Daniel H. Fowler's laboratory at the Experimental Transplantation Immunology Branch, NCI, NIH for post-doctoral research. 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 Reynolds, 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 into translational T regulatory engineering projects and biomarker discovery studies in cancer immunotherapy.
For recent publications please visit:
https://www.ncbi.nlm.nih.gov/pubmed/?term=amarnath shoba
Area of expertise
T cell Immunobiology, co-receptor biology, Immunotherapy, T cell engineering, Immune Tolerance
Active collaborators
Prof. Ruth Plummer, Newcastle University
Prof. Penny Lovat, Newcastle University
Prof.Eugene Healy, University of Southampton
Prof. Avan Sayer, Newcastle University
Dr. Marloes Peeters, Newcastle University
Dr. James Dawson, Newcastle University
Funding (Active)
Barbour PhD studentship
NC3R PhD Studentship
BRC/NIHR Project Award
Northern Accelerator Award
MRC Research Grant (Infections and immunity board)
Leo Foundation Future Leader Award EMEA
Patent
Use of PDL1 expressing cells to convert T cells into regulatory T cells. Patent number:9644179; Inventors:Dr. James L.Riley, Dr. Daniel H. Fowler and Dr. Shoba Amarnath.
Membership
British Society of Immunology
European Society of Dermatological Research
British Society of Investigative Dermatology
Manuscript/Grant Peer Review
Journals: Blood, Journal of clinical investigation, Cancer Research, Science Translational Medicine, Biology of blood and marrow transplantation, Stem Cells, European Journal of Immunology.
Funding Bodies: BBSRC, BBSRC Fellowship, Wellcome Trust Henry Dale Fellowship, Austria Science Fund (FWF).
We are always looking for post-docs and PhD so please do contact me if interested in working with us.
For any lab related resources/protocols please visit our laboratory website at
https://blogs.ncl.ac.uk/amarnath
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 co-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.
I have mentored numerous undergraduate, medical students, clinical fellows at the NIH.
I also lecture on Lymphocytes within the tumour microenvironment which is part of the curriculum for the M.Res Cell Signaling Module
So far the laboratory has trained 9 B.Sc students, 7 M.Res Students at Newcastle University
Currently, the laboratory consists of 2 PhD students working towards their thesis, 2 completed.
- Laba S, Mallett G, Amarnath S. The depths of PD-1 function within the tumor microenvironment beyond CD8+ T cells. Seminars in Cancer Biology 2021, epub ahead of print.
- Smith ALM, Whitehall JC, Bradshaw C, Gay D, Robertson F, Blain AP, Hudson G, Pyle A, Houghton D, Hunt M, Sampson JN, Stamp C, Mallett G, Amarnath S, Leslie J, Oakley F, Wilson L, Baker A, Russell OM, Johnson R, Richardson CA, Gupta B, McCallum I, McDonald SAC, Kelly S, Mathers JC, Heer R, Taylor RW, Perkins ND, Turnbull DM, Sansom OJ, Greaves LC. Age-associated mitochondrial DNA mutations cause metabolic remodeling that contributes to accelerated intestinal tumorigenesis. Nature Cancer 2020, 1, 976-989.
- Amarnath S, Brown ML. Harnessing proteases for T regulatory cell immunotherapy. European Journal of Immunology 2020, 50(6), 770-778.
- Mallett G, Patterson W, Payne M, Amarnath S. Isolation and Characterization of Innate Lymphoid Cells within the Murine Tumor Microenvironment. In: Methods in Molecular Biology. New York: Humana Press Inc, 2020, pp.153-164.
- Amarnath S. Protocols for Innate Lymphoid Cell Phenotypic and Functional Characterization: An Overview. In: Methods in Molecular Biology. New York: Humana Press Inc, 2020, pp.1-6.
- Amarnath S. Protocols for Innate Lymphoid Cell Phenotypic and Functional Characterization: An Overview. In: Amarnath, S, ed. Innate Lymphoid Cells. New York, NY, USA: Humana Press Inc, 2020, pp.1-6.
- Mallett G, Laurence A, Amarnath S. Programmed Cell Death-1 Receptor (PD-1)- Mediated Regulation of Innate Lymphoid Cells. International Journal of Molecular Science 2019, 20(11), 2836.
- 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 Kasteren SI, Laurence A, Bogyo M, Watts C, Shevach EM, Amarnath S. PD-1 inhibitory receptor downregulates 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), 1663-1678.
- 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.
- Fowler DH, Amarnath S. IL-27: A new target for GVHD prevention. Blood 2016, 128(16), 2003-2004.
- 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-R el in GVHD biology: A missing link. European Journal Of Immunology 2013, 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.
- 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.
- Amarnath S, Fowler DH. Harnessing autophagy for adoptive T cell therapy. Immunotherapy 2012, 4(1), 1-4.
- 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.
- 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, 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, 3(111), 111ra120.
- 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), 523-541.
- Amarnath S, Costanzo CM, Mariotti J, Ullman JL, Telford WG, Kapoor V, Riley JL, Levine BL, June CH, Fong T, Warner NL, Fowler DH. Regulatory T cells and human myeloid dendritic cells promote tolerance via programmed death ligand-1. PLoS Biology 2010, 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. Endogenous TGF-b is associated with induction of Foxp3 and regulation of HIV replication in TCR activated human CD4+CD25- T cells. Retrovirology 2007, 9(4), 57.
- Amarnath S, Dong L, Li J, Wu Y, Chen WJ. Endogenous TGF-β activation by reactive oxygen species is key to Foxp3 induction in TCR-stimulated and HIV-1-infected human CD4+CD25-T cells. Retrovirology 2007, 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.
- Liu Y, Amarnath S, Chen W. Requirement of CD28 signaling in homeostasis/survival of TGF-β converted CD4+CD25+ Tregs from thymic CD4+CD25- single positive T cells. Transplantation 2006, 82(7), 953-964.
- Amarnath SMP, Dyer CE, Ramesh A, Iwaugwu O, Drew PJ, Greenman J. In vitro quantification of the cytotoxic T lymphocyte response against human telomerase reverse transcriptase in breat cancer. International Journal of Oncology 2004, 25(1), 211-217.