Haematopoietic stem cell transplantation: Complement signalling pathway as a therapeutic target
Haematopoietic stem cell transplantation (HSCT) is a life saving therapy for blood cell malignancies. However, a substantial proportion of HSCT patients suffer from severe immune complications. Therefore, the main clinical and research challenge in HSCT is the immune response by donor’s transplanted blood cells to patient’s tissues, which is referred as Graft vs. Host Disease (GvHD).
Although complement pathway is generally acknowledged as an important arm of immune system, current knowledge on its potential role in GvHD is very limited. It has been recently reported that complement signalling via C3aR and C5aR plays a role in shaping the balance between T lymphocyte effector and T regulatory response, which in turn could determine the severity of GvHD and the success of transplantation. Although C3aR and C5aR are also expressed on neutrophils and monocytes, the role of complement signalling in these cells during GvHD type immune response has not been studied.
This project aims to investigate the role of complement receptors C3aR and C5aR in haematopoietic stem cell transplantation (HSCT) and its main pathological complication Graft vs. Host Disease (GvHD).
T lymphocytes are regarded as the key drivers of GvHD pathology. Although the majority of current therapeutic strategies are aimed at T cells, current treatments are non-selective, cause general immune-suppression and have limited efficacy. Therefore, the need for new therapeutic strategies is widely acknowledged. We aim to investigate the effects of targeting T cells by blocking complement signalling pathways, primarily C3aR, C5aR and newly discovered intracellular C3 signalling. This will be addressed using in vitro models of HSCT/GvHD and patient samples. The student will develop skills in research techniques, ability to design experiments, analyse, interpret and present complex research data. The student will also be encouraged to participate in the University of Westminster Graduate School training programme and to obtain a Postgraduate Certificate in teaching and learning.
The Studentship consists of a fee waiver and a stipend of £16,000 per annum. Successful candidates will be expected to undertake some teaching duties.
Jurcevic S, Humfrey C, Uddin M, Warrington S, Larsson B, Keen C. The effect of a selective CXCR2 antagonist (AZD5069) on human blood neutrophil count and innate immune functions. Br J Clin Pharmacol 2015, 80: 1324-1336.
Shariff H, Greenlaw RE, Meader L, Gardner N, Yagita H, Coccia M, Mamode N and Jurcevic S. The Role of the Fc Region in CD70-specific Antibody Effects on Cardiac Transplant Survival. Transplantation 2011, 92: 1194-201.
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