Research

My primary interest is in the role of B cell receptor (BCR) in the development of B cell malignancies. The immunoglobulin (Ig) – the largest component of BCR – is a key molecule for B cells. Individually constructed during antigen-driven somatic hypermutation of rearranged immunoglobulin V(D)J genes, this receptor is "designed" to recognise a specific antigen. The analysis of the Ig genes allows us to reveal a clonal history of a malignant B cell tracking down a cell of origin.

The BCR signalling, a part of the support received by the CLL microenvironment, provides favourable conditions for CLL cells' survival and eventually, disease progression. Therefore, the dissection of the BCR signalling provides us clues to possible targets for therapeutic attack and can help developing new approaches to the treatment of the B-cell malignancies.

Currently, I am leading on a number of research projects looking into the development of B-cell malignancies and the role of the B-cell receptor in B-cell lymphoma and leukaemia.

Other Activities

• Member of the European Research Initiative on CLL (ERIC)

Major Funding

• 2016-2018- Leuka, John Goldman Fellowship for Future Science, A novel B-cell receptor - nuclear repressor ZEB2 axis that defines the clinical outcome in chronic lymphocytic leukaemia, £100,000
• 2016-2020- Barts Charity, Strategic Research Grant, Composition of the peripheral blood of CLL patients. Interactions, activation and signaling capacity of B and T-cells, £77,487

Recent Publications

IGHV sequencing reveals acquired N-glycosylation sites as a clonal and stable event during follicular lymphoma evolution. Odabashian M, Carlotti E, Araf S et al. Blood (2020) (2)
https://www.ncbi.nlm.nih.gov/pubmed/31932843

PEITC-mediated inhibition of mRNA translation is associated with both inhibition of mTORC1 and increased eIF2α phosphorylation in established cell lines and primary human leukemia cells Yeomans A, Lemm E, Wilmore S et al. Oncotarget (2016) 7(1) 74807-74819

Engagement of the B-cell receptor of chronic lymphocytic leukemia cells drives global and MYC-specific mRNA translation Yeomans A, Thirdborough SM, Valle-Argos B et al. Blood (2016) 127(13) 449-457

T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice Oldreive CE, Skowronska A, Davies NJ et al. Disease Models & Mechanisms (2015) 8(13) 1401-1412

Lectin binding to surface Ig variable regions provides a universal persistent activating signal for follicular lymphoma cells Linley A, Krysov S, Ponzoni M et al. Blood (2015) 126(7) 1902-1910

Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma Schneider D, Dühren-von Minden M, Alkhatib A et al. Blood (2015) 125(13) 3287-3296

Stimulation of surface IgM of chronic lymphocytic leukemia cells induces an unfolded protein response dependent on BTK and SYK Krysov S, Steele AJ, Coelho V et al. Blood (2014) 124(7) 3101-3109

The outcome of B-cell receptor signaling in chronic lymphocytic leukemia: proliferation or anergy Packham G, Krysov S, Allen A et al. Haematologica (2014) 99(13) 1138-1148

Identification in CLL of circulating intraclonal subgroups with varying B-cell receptor expression and function Coelho V, Krysov S, Steele A et al. Blood (2013) 122(13) 2664-2672

Mechanisms and clinical significance of BIM phosphorylation in chronic lymphocytic leukemia Paterson A, Mockridge CI, Adams JE et al. Blood (2012) 119(13) 1726-1736

Team

Postdoctoral Researchers in this group
Dr Filomena Spada

PhD Students
Ms Mariette Odabashian, Ms Nicola Maxine Joseph

Biography

I studied biology at the Tomsk State University (MSc Biology, 1996, Tomsk, Russia). I then completed my PhD project at the Institute of Clinical Immunology (PhD, 2001, Novosibirsk, Russia). In 2002 I joined the Tenovus Research Laboratory at the University of Southampton. In 2007 I transferred, within Southampton, and joined the Chronic lymphocytic leukemia project at Cancer Research Clinical Centre. In May 2014 I was appointed Lecturer at Barts Cancer Institute, QMUL.