Staff Profile

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 multiple collaborations, 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, ILCs

Active collaborators 

Prof. John Isaacs, Newcastle University

Prof. Nick Reynolds, Newcastle University

Prof. Derek Mann, Newcastle University

Prof. Helen Reeves, Newcastle University

Prof. Ruth Plummer, Newcastle University

Prof. Penny Lovat, Newcastle University

Prof. Avan Sayer, Newcastle University

Dr. Antoneta Granic, Newcastle University

Dr. Marloes Peeters, Newcastle University

Dr. James Dawson, Newcastle University

Dr. Giuseppe Sciume, LaSapienza University, Rome

Prof. Giovanna Lombardi, KCL

Prof. Eugene Healy, University of Southampton

Dr. Cristiano Scotta, KCL

Dr. Arian Laurence, UCLH

Dr. Han-Yu Shih, NIH

Funding (Active)

BRC/NIHR (Skin/oral theme)

Lister Prize

Barbour PhD studentship

NC3R PhD Studentship

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 and ILC function in inflammation and cancer. Our research suggests that coreceptors function in a more collective regulatory manner than previously defined and current work in the laboratory is focussed on identifying the landscape of checkpoint receptors that are controlled by PD-1. Developing a landscape approach to checkpoint receptors will not only elucidate immune tolerance mechanisms but also identify key checkpoints that could be valuable in treating cancer.

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). 

Recently, we have demonstrated that a previously undefined population of Innate Lymphoid Cells with a type 1 signature is controlled by PD-1 within the melanoma and cutaneous squamous cell carcinoma microenvironment (Lim et al, PNAS, 2023).

I provide pastoral support to a number of UG tutees, and also participate in teaching at the UG, M.Res and Graduate level students.

I also lecture on Lymphocytes within the tumour microenvironment which is part of the curriculum for the M.Res Cell Signaling Module 

• Articles

  • Lim JX, Lai CY, Mallett GE, McDonald D, Hulme G, Laba S, Shapanis A, Payne M, Patterson W, Alexander M, Coxhead J, Filby A, Plummer R, Lovat PE, Sciume G, Healy E, Amarnath S. Programmed cell death-1 receptor-mediated regulation of Tbet⁺NK1.1^- innate lymphoid cells within the tumor microenvironment. Proceedings of the National Academy of Sciences of the United States of America 2023, 120(18), e2216587120.
  • Laba S, Mallett G, Amarnath S. The depths of PD-1 function within the tumor microenvironment beyond CD8+ T cells. Seminars in Cancer Biology 2022, 86(2), 1045-1055.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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, 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 T_H1 Cells Into Regulatory T Cells. Science Translational Medicine 2011, 3(111), 111ra120.
  • 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.
  • 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.
  • 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, 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.
  • 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.
  • 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.

• Book Chapters

  • 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, 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.

• Conference Proceedings (inc. Abstract)

  • Singla P, Broughton T, Sullivan MV, Garg S, Canfarotta F, Turner NW, Velliou E, Amarnath S, Peeters M. Engineered Double-Imprinted Nanoparticles for Targeted Drug Delivery to Breast Cancer. In: Controlled Released Society (CRS) 2023 Annual Meeting. 2023, Las Vegas, Nevada, USA: Controlled Released Society (CRS).

• Note

  • Fowler DH, Amarnath S. IL-27: A new target for GVHD prevention. Blood 2016, 128(16), 2003-2004.

• Reviews

  • Smith KJ, Sciume G, Amarnath S. Twenty-One Flavours of Type 1 innate lymphoid cells with PD-1 (Programmed Cell Death-1 Receptor) Sprinkles. Discovery Immunology 2023, 2(1).
  • 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.
  • Amarnath S, Barrett AJ. Mesenchymal stromal cells:heroes or non-combatants. Cytotherapy 2013, 15(3), 253-254.
  • Amarnath S. c-R el in GVHD biology: A missing link. European Journal Of Immunology 2013, 43(9), 2255-2158.
  • Amarnath S, Fowler DH. Harnessing autophagy for adoptive T cell therapy. Immunotherapy 2012, 4(1), 1-4.