Frances M. Gotch
e-mail: f.gotch AT imperial.ac.uk
affiliation: Imperial College London
research area(s): Immunity And Infection, Experimental Medicine
Course:
Basic and Applied Immunology
University/Istitution: Università Vita-Salute San Raffaele
University/Istitution: Università Vita-Salute San Raffaele
Professor Gotch is professor of Immunology at Imperial College, London. She received a PhD from the University of Oxford in 1987, and became FRCPath in 2002. Senior staff within her group include Drs Peter Kelleher, Adriano Boasso, Nesrina Imami, Steve Patterson and Jill Gilmour. Frances Gotch acts as an invited reviewer for many journals and regularly reviews grant proposals for national and international funding bodies.
Within the department we have expertise in cellular immunology and molecular immunology with the emphasis on investigations into the mechanisms and importance of T-cell activity in disease. Studies have and are being undertaken with influenza, CMV, EBV, HIV.1, HIV.2, SIV, HHV8 and malaria.
The purpose of many of the studies which are currently being undertaken is to identify HIV-specific immunological functions in vaccinated, infected (treated and untreated) and high risk non-infected individuals, to understand the fine specificity of these immunological functions, and therefore to be able to quantitate and qualitate immunological parameters in infected individuals, in vaccinated individuals, in high risk non-infected individuals, or after therapeutic intervention during disease. Our work has a high international profile and has been published in peer reviewed journals.
Part of the work includes an important collaboration with the Uganda Virus Research Institute, Entebbe, Uganda. The group is involved in vaccine trials both in non-human primates and in man, and we are collaborating with biotechnology companies in Britain, in Europe and in the USA in the immunological monitoring of trials of promising vaccines. FG is the principal investigator for the International AIDs Vaccine Initiative Core Immunology Laboratory in the UK with the responsibility for monitoring many vaccine trials world wide.
The purpose of many of the studies which are currently being undertaken is to identify HIV-specific immunological functions in vaccinated, infected (treated and untreated) and high risk non-infected individuals, to understand the fine specificity of these immunological functions, and therefore to be able to quantitate and qualitate immunological parameters in infected individuals, in vaccinated individuals, in high risk non-infected individuals, or after therapeutic intervention during disease. Our work has a high international profile and has been published in peer reviewed journals.
Part of the work includes an important collaboration with the Uganda Virus Research Institute, Entebbe, Uganda. The group is involved in vaccine trials both in non-human primates and in man, and we are collaborating with biotechnology companies in Britain, in Europe and in the USA in the immunological monitoring of trials of promising vaccines. FG is the principal investigator for the International AIDs Vaccine Initiative Core Immunology Laboratory in the UK with the responsibility for monitoring many vaccine trials world wide.
>230 peer reviewed papers from 1971-present.
Robey RC, Mletzko S, Bower M, Meys R, Boffito M, Nelson M, Bunker CB, Gotch FM. Ex-Vivo Recognition of Late-Lytic CD8 Epitopes Specific for Kaposi's Sarcoma-Associated Herpesvirus (KSHV) by HIV/KSHV-Coinfected Individuals. Viral Immunol. 2011 Jun;24(3):211-20.
Matthews NC, Goodier MR, Robey RC, Bower M, Gotch FM. Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells. Eur J Immunol. 2011 Jul;41(7):1958-68. doi: 10.1002/eji.201040661.
Robey RC, Lagos D, Gratrix F, Henderson S, Matthews NC, Vart RJ, Bower M, Boshoff C, Gotch FM. The CD8 and CD4 T-cell response against Kaposi's sarcoma-associated herpesvirus is skewed towards early and late lytic antigens. PLoS One. 2009 Jun 17;4(6):e5890.
Townsend AR, Rothbard J, Gotch FM, Bahadur G, Wraith D, McMichael AJ. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. 1986. J Immunol. 2006 May 1;176(9):5141-50.
Robey RC, Mletzko S, Bower M, Meys R, Boffito M, Nelson M, Bunker CB, Gotch FM. Ex-Vivo Recognition of Late-Lytic CD8 Epitopes Specific for Kaposi's Sarcoma-Associated Herpesvirus (KSHV) by HIV/KSHV-Coinfected Individuals. Viral Immunol. 2011 Jun;24(3):211-20.
Matthews NC, Goodier MR, Robey RC, Bower M, Gotch FM. Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells. Eur J Immunol. 2011 Jul;41(7):1958-68. doi: 10.1002/eji.201040661.
Robey RC, Lagos D, Gratrix F, Henderson S, Matthews NC, Vart RJ, Bower M, Boshoff C, Gotch FM. The CD8 and CD4 T-cell response against Kaposi's sarcoma-associated herpesvirus is skewed towards early and late lytic antigens. PLoS One. 2009 Jun 17;4(6):e5890.
Townsend AR, Rothbard J, Gotch FM, Bahadur G, Wraith D, McMichael AJ. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. 1986. J Immunol. 2006 May 1;176(9):5141-50.
Project Title:
Novel Virological and genetic correlates with HIV disease progression
Long term non-progressors (LTNP) are HIV-1 infected individuals who retain fully functional CD4 and CD8 HIV-1 specific T cells, thereby maintaining a robust IFNγ-, IL2- and perforin- producing HIV-1- specific T-cell repertoire which is competent to proliferate. LTNPs have preserved, strong and broad responses to HIV-1 with the consequent ability to control HIV replication in the absence of drug
treatment for extensive periods of time (at least 7 years). Thus LTNPs do not suffer from profound and on-going immunodeficiency that afflicts the vast majority of chronically HIV infected patients. The purpose of this study, which is highly complementary to other studies being carried out within the departments in London and at the San Raffaele Scientific Institute in Milan, is to further establish
genetic and virologic differences between LTNPs and chronically infected patients, and to clarify the contribution that viral variation and genetic variation may make to disease pathology. It is hoped that comparisons of virologic and genetic profiles of LTNPs with those of chronic progressors will yield insights into the potential immunotherapeutic creation of LTNP status in chronically infected
individuals. Such status would result from reversal of the anergic immunological state which we and others observe in chronic progression, and should improve long-term cellular functional memory responses, resulting in greater viral control and slower disease progression.
Initial aims of the study:
1. To establish whether LTNP status is dependent on lack of viral fitness of the autologous virus in these patients we propose to assess viral replication fitness of autologous virus in both LTNP and chronically infected individuals by quantifying uncomplexed p24 in the sample (which may be obtained from peripheral blood or from mucosal samples), and intracellular HIV-1 p24 expression.
2. To elucidate which genes are associated with LTNP status we will carry out microarray analysis of samples from a well defined cohort of LTNP, chronically infected individuals, and, seronegative control using cellular RNA.
treatment for extensive periods of time (at least 7 years). Thus LTNPs do not suffer from profound and on-going immunodeficiency that afflicts the vast majority of chronically HIV infected patients. The purpose of this study, which is highly complementary to other studies being carried out within the departments in London and at the San Raffaele Scientific Institute in Milan, is to further establish
genetic and virologic differences between LTNPs and chronically infected patients, and to clarify the contribution that viral variation and genetic variation may make to disease pathology. It is hoped that comparisons of virologic and genetic profiles of LTNPs with those of chronic progressors will yield insights into the potential immunotherapeutic creation of LTNP status in chronically infected
individuals. Such status would result from reversal of the anergic immunological state which we and others observe in chronic progression, and should improve long-term cellular functional memory responses, resulting in greater viral control and slower disease progression.
Initial aims of the study:
1. To establish whether LTNP status is dependent on lack of viral fitness of the autologous virus in these patients we propose to assess viral replication fitness of autologous virus in both LTNP and chronically infected individuals by quantifying uncomplexed p24 in the sample (which may be obtained from peripheral blood or from mucosal samples), and intracellular HIV-1 p24 expression.
2. To elucidate which genes are associated with LTNP status we will carry out microarray analysis of samples from a well defined cohort of LTNP, chronically infected individuals, and, seronegative control using cellular RNA.