Summary
James Harker completed his BSc in Biochemistry and MRes in Molecular Mechanisms of Infection at Imperial College London . He subsequently undertook a MRC sponsored PhD in the lab of Professor Peter Openshaw at St Marys Hospital studying the immune response to Respiratory Syncytial Virus, where he was particularly focused on distinct immune responses elicited by this virus in infants versus adults and the role cytokines played in this process.
On completion of his PhD he moved to the west coast of the U.S. to take up a postdoctoral position at the University of California San Diego in the lab of Dr. Elina Zuniga studying inhibitory immune pathways active during chronic viral infections. Using a murine model of chronic viral infection he made a novel observation regarding the high frequency of a subset of CD4 T cells, T follicular helper cells, at late stages of chronic infection, findings later translated into human infections including HIV-1 and Hepatitis C virus. T follicular helper cells are vital in promoting high affinity antibody production by B cells and James determined that the cytokine interleukin-6 played an essential role in this process and was critical for the development of anti-viral antibodies and viral containment. In 2011 he was awarded an Irvington Institute fellowship from the Cancer Research Institute to extend his research into the interplay between the IL-6 family of cytokines and T follicular helper cells.
In 2013 James was awarded a Sir Henry Dale Fellowship by the Wellcome Trust and the Royal Society to establish a research group investigating the molecular mechanisms involved in the generation of T follicular helper cells, and in October, 2013 he re-joined Imperial College London as a member of the Section of Leukocyte Biology within the National Heart and Lung Institute. James's current research focuses on studying the development of humoral immunity in response to respiratory viral infections and the effects of age on this process.
Selected Publications
Journal Articles
Pyle CJ, Labeur-Iurman L, Groves HT, et al., 2021, Enhanced IL-2 in early life limits the development of TFH and protective antiviral immunity, Journal of Experimental Medicine, Vol:218, ISSN:0022-1007
Uwadiae F, Pyle C, Walker S, et al., 2019, Targeting the ICOS/ICOS-L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease, Allergy, Vol:74, ISSN:0105-4538, Pages:650-662
Greczmiel U, Kräutler NJ, Pedrioli A, et al., 2017, Sustained T follicular helper cell response is essential for control of chronic viral infection., Science Immunology, Vol:2, ISSN:2470-9468
Pyle CJ, Uwadiae FI, Swieboda DP, et al., 2017, Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology., PLOS Pathogens, Vol:13, ISSN:1553-7366
Harker J, Wong KA, Dolgoter A, et al., 2015, Cell-intrinsic gp130 Signaling on CD4+ T cells Shapes Long-lasting Antiviral Immunity, Journal of Immunology, ISSN:1550-6606
Harker JA, Yamaguchi Y, Culley FJ, et al., 2014, Delayed sequelae of neonatal RSV infection are dependent on cells of the innate immune system, Journal of Virology, ISSN:0022-538X
Harker JA, Dolgoter A, Zuniga EI, 2013, Cell-Intrinsic IL-27 and gp130 Cytokine Receptor Signaling Regulates Virus-Specific CD4(+) T Cell Responses and Viral Control during Chronic Infection, Immunity, Vol:39, ISSN:1074-7613, Pages:548-559
Tregoning JS, Wang BL, McDonald JU, et al., 2013, Neonatal antibody responses are attenuated by interferon-gamma produced by NK and T cells during RSV infection, Proceedings of the National Academy of Sciences of the United States of America, Vol:110, ISSN:0027-8424, Pages:5576-5581
Harker JA, Lewis GM, Mack L, et al., 2011, Late Interleukin-6 Escalates T Follicular Helper Cell Responses and Controls a Chronic Viral Infection, Science, Vol:334, ISSN:0036-8075, Pages:825-829
Lee DCP, Harker JAE, Tregoning JS, et al., 2010, CD25(+) Natural Regulatory T Cells Are Critical in Limiting Innate and Adaptive Immunity and Resolving Disease following Respiratory Syncytial Virus Infection, Journal of Virology, Vol:84, ISSN:0022-538X, Pages:8790-8798
Harker JA, Lee DCP, Yamaguchi Y, et al., 2010, Delivery of Cytokines by Recombinant Virus in Early Life Alters the Immune Response to Adult Lung Infection, Journal of Virology, Vol:84, ISSN:0022-538X, Pages:5294-5302
Pribul PK, Harker J, Wang B, et al., 2008, Alveolar macrophages are a major determinant of early responses to viral lung infection but do not influence subsequent disease development, Journal of Virology, Vol:82, ISSN:0022-538X, Pages:4441-4448