About the Project
Chronic Lymphocytic Leukaemia (CLL) is the most frequent adult leukaemia in the western world with an estimated cost to the society of £1 billion/year. CLL is highly heterogeneous, with the course of the disease ranging from indolent to aggressive. Accurate prognosis is essential for effective disease management. Introducing novel biomarkers to the selection of patients for the first-line and subsequent therapies is therefore of a paramount importance.
We have previously established the important role of the toll-like receptor CD180/RP105 in CLL cell signaling and survival. The aim of this project is to assess for the first time the patterns of CD180 expression and signaling, their effect on B cell receptor (BCR), in different CLL prognostic groups based on genetic abnormalities, chromosomal instability, phenotype and clinical indicators, resulting in a computerized model.
By establishing cross-talk between CD180 and the BCR signaling, we will identify subgroups of patients who would benefit the most from the molecular therapies, thus reducing the toxicity of the treatment, enhancing precision therapy and its cost-efficiency.
The supervisory team are well established experts in prognostication and immunotherapy of CLL, cytogenomic applications and computer modelling. The project is a part of an ongoing collaboration with the UCL Cancer Centre.
Informal enquiries to: Dr [Email Address Removed]
References
Nino Porakishvili, Uzma Sayed, Emanuela Volpi, Kristina Zaitseva, Edward A.Clark, Kanti R.Rai, Amit Nathwani, Nicholas Chiorazziand Peter M.Lydyard. Synergistic pro-apoptotic signalling pathways mediated through CD180 toll-like receptor and sIgD in Chronic Lymphocytic Leukaemia (CLL) cells. Paper in preparation.
Porakishvili Nino, Vispute Ketki, Rajakaruna Nadeeka, Andrew Steele, Kulikova Nina, Clark Edward A., Rai Kanti R., Nathwani Amit, Damle Rajendra N., Chiorazzi Nicholas and Lydyard, Peter M. Rewiring of sIgM-mediated intracellular signaling through theCD180 Toll-like receptor. Molecular Medicine, 2015, 21: 46-57.
Porakishvili Nino, MemonAzka, VisputeKetki, Kulikova Nina, Clark Edward A., Rai Kanti R., NathwaniAmit, DamleRajendra N., ChiorazziNicholas and Lydyard, Peter M. CD180 functions in activation, survival and cycling of B chronic lymphocytic leukaemia cells. Br J Haematol, 2011, 153:486–498.
JA Walton, PM Lydyard, A Nathwani,VEmery, A Akbar, MJ Glennie and N Porakishvili. Patients with B cell chronic lymphocytic leukaemia have an expanded population of CD4+ perforin expressing T cells enriched for human cytomegalovirus specificity and an effector-memory phenotype. Br J Haematol. 2010, 148, 274-84.
A Warford and E Volpi. In situ Hybridization: Key Concepts and Applications, 2017. In: Orchard G. and Nation B. (eds), “Histopathology” (2nd Edition), Fundamentals of Biomedical Sciences, Oxford University Press.
M Usman and EVolpi. DNA damage in obesity: initiator, promoter and predictor of cancer. Reviews in Mutation Research, 2018, 778: 23-37.
R Real, M Peter, A Trabalza, S Khan, MA Smith, J Dopp, SJ Barnes, A Momoh, A Strano, E Volpi, G Knott, FJ Livesey and V De Paola, 2018. In vivo modeling of human neuron dynamics and Down syndrome. Science, 2018, 362:
A Warford and E. Volpi, 2019. Intact sample analysis. In: Warford A. and Presnaeu N. (eds), “Molecular Diagnostics”, Fundamentals of Biomedical Sciences, Oxford University Press.
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