Dr Melania Capasso

PhD
Centre: Cancer and Inflammation
Honorary Lecturer
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QMUL Directory


I research the basic functions of normal and malignant B cells, with the aim of translating this knowledge into new therapies.

Research Details

A strong interest of my group is understanding how the voltage-gated proton channel, HVCN1, supports the growth of B cell malignancies such as Chronic Lymphocytic Leukaemia (CLL) and Diffuse Large B-Cell Lymphoma (DLBCL). These types of cancer receive positive stimuli through their B Cell Receptor (BCR), just like normal B cells. I have already described how HVCN1 sustains BCR stimulation, activation of signalling pathways and energy metabolism in B cells (Capasso et al., Nat Immunol, 2010) and I am now extending the analysis to their malignant counterpart.

Another interest is to characterise the role played by HVCN1 in other immune cells and whether this could be exploited therapeutically.

In addition, I am investigating how immune cells support tumour growth, especially in ovarian and pancreatic cancer, with strong collaborative links within the Barts Cancer Institute.

Profile

I joined Barts Cancer Institute in April 2010.

I studied Medicinal Chemistry at the University of Naples, Federico II, in Italy and completed my PhD in naturally occurring antioxidants from the same University in 2003. During my PhD, I was awarded a postgraduate European Commission Marie Curie fellowship to join the BBSRC Institute of Food Research in Norwich for a year. I then moved to a postdoctoral position at the University of Nottingham, where I investigated the suppressive phenotype induced in CD4+ T cells by costimulation via CD55, a complement receptor protein.

In 2006, I started a postdoc in the MRC Toxicology Unit in Leicester to study membrane proteins in normal and malignant B lymphocytes. Here I uncovered the role of the voltage-gated proton channel, HVCN1, in B-cell receptor activation and the effect of a deregulated cytokine receptor, CRLF2, in B-cell leukaemia.

Funding

  

 

2015-2017 Pancreatic Cancer Research Fund "Defining the role of regulatory B cells in pancreatic cancer"
£112,478
2015-2018 Willoughby Fund for Inflammatory Research  PhD studentship: "Regulation of inflammatory pathways in microglia, the innate immune cells of the brain"
£66,171
2015 QMUL Life Sciences Initiative "Characterising the impact of immunoglobulins on tumour stiffness"
Collaboration with Prof. Martin Knight (School of Engineering and Materials Science)
2013-2016 Royal Embassy of Saudi Arabia PhD project: "The role of proton channels in aberrant glycosylation of blood cancers"
£130,000
2012-2017 Leukaemia and Lymphoma Research Bennett Fellowship "HVCN1 in B-cell malignancies, a potential novel therapeutic target"
£580,000
2012-2016 BBSRC Industrial Case Award, GSK Oncology CASE PhD Studentship: "Investigating the voltage-gated proton channel HVCN1 as a target for lymphoma treatment"
£100,000, £32,000
2012-2015 Medical Research Council PhD Studentship: "Elucidating the role of B cells in pancreatic cancer"
£64,500

Key Publications

McClanahan F, Riches JC, Miller S, Day WP, Kotsiou E, Neuberg D, Croce CM, Capasso M, Gribben JG. Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model. (2015) Blood. 126(2):212-21. PMID: 25979947

Hondares E, Brown M, Musset B, Morgan D, Cherny VV, et al. Enhanced activation of an amino-terminally truncated isoform of voltage-gated proton channel HVCN1 enriched in malignant B cells. (2014) PNAS 111(50):18078-83 PMID:

Capasso M, Bhamrah MK, Henley T, Boyd RS, Langlais C, Cain K. HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species. (2010) Nat Immunol. 11(3):265-72. PMID: 20139987

Musset B*, Capasso M*, Cherny VV, Morgan D, Bhamrah M, Dyer MJ. Identification of Thr29 as a critical phosphorylation site that activates the human proton channel Hvcn1 in leukocytes. J Biol Chem. (2010) 285(8):5117-21. PMID: 20037153


Further Publications

For additional publications, please click here.


I research the basic functions of normal and malignant B cells, with the aim of translating this knowledge into new therapies.

External Activities

  • Member of Biological Sciences Research Grant Board, Royal Society, 2013 – 2017
  • Reviewer for L’Oreal-Unesco Fellowships for Women in Science
  • Member of the Biophysical Society
  • Member of the British Society for Immunology
  • STEMNET Ambassador
  • Member of Queen Mary University of London Senate, 2013 – 2017

News

See other researchers working on:

Cell Signalling Immunology Leukaemia Lymphoma Metabolism
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