Overview: Impaired peripheral immune responses, named immuneparesis and sepsis susceptibility are central to the pathogenesis and outcome of acute and chronic liver diseases. The Liver Immunology Research group aims to investigate underlying defective immune mechanisms responsible for the marked predisposition to infection observed in patients with acute and chronic liver failure.
Current research: Dr Wafa Khamri research focus is on investigating the impact of defective adaptive immune responses in patients with acute and chronic liver disease complications. Her current research is divided into two themes:
1. Investigating the role of peripheral suppressor T and B cells in failure to mount proper adaptive immune mediated control of infections in chronic liver failure
2. Delineating key molecular and metabolic drivers that are responsible for the induction, expansion and propagation of potent immunosuppressive/ tolerogenic activity in patients with liver failure
Research goal: Identifying dysregulation of adaptive immunity will enhance the ability to identify key targeted immunotherapy-based strategies with the aim of restoring pivotal immune responses to infections and improve patient outcome.
Funding: Dr Khamri was awarded an NIHR Imperial BRC Institute for Translational Medicine and Therapeutics (ITMAT) projects for developing capacity. Her research funders include the Rosetrees Charitable Trust, MRC & Sociéte Nationale Française de GastroEntérologie .
Other research interests:
Evaluating the role of myeloid immune checkpoint modulation in hepatocellular carcinoma (HCC) (Dr Sujit Mukherjee PhD project funded by the Welcome Trust)
Understanding the pathogenesis of immune checkpoint inhibitor–induced (CPI) hepatitis (Ms Cathrin Gudd PhD project funded by the Rosetrees Trust and the Royal Marsden Cancer Charity)
Collaborative pharmaceutical projects: In collaboration with GlaxSmithKline: Investigating the effect of Bromodomain (BRD) and Extra-Terminal (BET) family inhibitor in peripheral blood mononuclear cells from patients with inflammatory liver indications.
Previous research: Dr Khamri former research contributed to the field of surfactant protein D (SP-D) with the original observations on SP-D and its interaction with Helicobacter and has demonstrated the role of SP-D in mediating immune responses to Helicobacter infection in the gastric mucosa. In addition, she worked on Helicobacter as a model for chronic infection and explored its interaction with dendritic cells and subsequently induced T cell responses.
Teaching: Dr Khamri is a Fellow of the Higher Education Academy. As well as supervising undergraduate and postgraduate students, she is a module co-leader for the Gastroenterology & Hepatology BSc.
et al., 2021, Activation and transcriptional profile of monocytes and CD8+ T cells are altered in checkpoint inhibitor-related hepatitis, Journal of Hepatology, ISSN:0168-8278, Pages:1-1
et al., 2020, PD-1 blockade improves Kupffer cell bacterial clearance in acute liver injury, Journal of Clinical Investigation, Vol:131, ISSN:0021-9738, Pages:1-16
et al., 2019, CD8+ T cells from patients with cirrhosis display a phenotype that may contribute to cirrhosis-associated immune dysfunction, Ebiomedicine, Vol:49, ISSN:2352-3964, Pages:258-268
et al., 2018, CD14+CD15-HLA-DR- myeloid-derived suppressor cells impair antimicrobial responses in patients with acute-on-chronic liver failure, Gut, Vol:67, ISSN:1468-3288, Pages:1155-1167
et al., 2017, MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure, Gut, Vol:67, ISSN:1468-3288, Pages:333-347