Theme 1: Understanding how HIV infection reactivates TB.
Three specific projects include mapping the fine specificity, function and evolution of TB-specific CD4 T cell responses to epitopes on autologous circulating strains derived through deep sequencing; identifying and understanding host factors that render antigen-specific T cell subsets susceptible to HIV infection in HIV-TB coinfected hosts and elucidating pathways that contribute to Treg/Th17 imbalance in HIV, TB and HIV-TB coinfection.
Theme 2: Pathways to modulate and enhance the HIV and TB-specific T cell response in vivo:
Specific projects include: Immune profiling of M.tb-specific responses to understand efficacy of BCG revaccination of young adults vulnerable to TB in an HIV-TB endemic region of India (major collaborators: Drs Julie McElrath/Ken Smith/Stephen D’Rosa, Fred Hutchinson Research Centre, Seattle, USA) and elucidating the immune benefits of vitamin D adjunct therapy in HIV-TB coinfection (major collaborators: Dr Barry Peters, KCL/ Prof. Catherine Hawrylowicz, KCL).
Theme 3: Host pathogen interactions: specific projects based on novel factors identified in my lab
My lab previously identified WFDC1/ps20, a member of the ancient Whey Acidic Protein family, to be expressed in human CD4 T cells and showed that it played a role in promoting HIV infection by increasing cellular adhesion through increased ICAM-1 expression. We are currently investigating the more fundamental roles of this protein in cellular proliferation and T-cell effector function using functional genomics approaches and with collaborators studying the wfdc1 null mouse in infection model systems.