How do CD4+ T cells preserve memories during malaria?
The Haque Group are funded by the Australian NHMRC to discover new molecular mechanisms that govern the transition from effector to memory states in antigen-specific CD4+ T cells. We focus on experimental blood-stage malaria, with the ultimate goal of developing new strategies that boost naturally-acquired immunological memory and vaccine-mediated immunity to this disease. Currently, we apply single-cell transcriptomics and epigenomics technologies, computational modelling, and experimental target validation in vivo to reconstruct the dynamic process of cellular change within CD4+ T cells.
CD4+ T cells in acute Graft-versus-Host Disease
The Haque group are examining how donor-derived CD4+ T cells after allogeneic hematopoietic stem cell transplantation, differentiate into pro-inflammatory, regulatory and quiescent cell states in the gastro-intestinal tract, thus controlling the severity of Graft-versus-Host Disease. In experimental in vivo models, we find rapid emergence of TCF1hi quiescent T cells that migrate to the gut, and retain a capacity to mount secondary effector responses therein. To translate these findings into humans, we are applying scRNA-seq to examine peripheral blood immune responses in Phase III clinical trials for prevention of acute GVHD.
Do malaria parasites sense and respond to the host during infection?
The Haque Group are interested not only in how the host immune response develops during blood-stage malaria, but also how the parasite itself responds to being within the host. We previously found evidence of host-mediated impairment of parasite maturation in experimental in vivo models. Currently, we are testing the hypothesis that parasites sense inhibitory factors released into the bloodstream by the the host, and respond by altering their transcriptional programs, which leads to slowed population growth of parasites within red blood cells.
Ashraful Haque completed a PhD on Salmonella pathogenesis in 2002, with Gordon Dougan at Imperial College, London. After a post-doctoral fellowship on immune responses to the bacterium, Burkholderia pseudomallei, at the London School of Hygiene & Tropical Medicine, he moved to Australia in 2005 to work on parasitic infections at QIMR in Brisbane, with Christian Engwerda. He received his first NHMRC grant in 2010, and started a research group at QIMR Berghofer in 2012. With NHMRC Project and Ideas Grants, and ARC Discovery funding, he has studied host/parasite interactions in blood-stage malaria, with a specific interest in single-cell genomics.