Dr Melania Capasso
Research Interests
Dr Melania Capasso's main research themes are in: Cancer Cell Biology, Cancer Immunology, Cell Signalling, Haematological Malignancies, Leukaemia and Lymphoma
My main research interest is to characterise the basic functions of normal and malignant B cells, with the aim of translating basic/fundamental discoveries into new therapeutic approaches. In particular, I aim to understand how normal and malignant B cells are regulated by the gene, HVCN1, which codes for the hydrogen voltage-gated proton channel, and is highly expressed in immune tissues.
B cells and some types of B-cell cancers receive positive stimuli via their B-cell receptor (BCR). I have described how HVCN1 supports BCR stimulation and downstream activation of signalling pathways and energy metabolism (Capasso et al., Nat Immunol, 2010). One of my current interests is to determine if HVCN1 also plays a role in B cell differentiation to plasma cells, the cells responsible for antibody production.
Another interest is to dissect how HVCN1 enhances tumours that maintain high HVCN1 expression, such as Chronic Lymphocytic Leukaemia (CLL) and Diffuse Large B-Cell Lymphoma (DLBCL). These tumours are known to rely on BCR survival signals and I am currently investigating whether they utilise proton channels to sustain their growth and survival.
Profile
I Joined Barts Cancer Institute in April 2010.
I studied Pharmaceutical Chemistry at the University of Naples, Federico II, 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 joined the MRC Toxicology Unit in Leicester to investigate the role of membrane proteins in normal and malignant B lymphocytes. Here I characterised 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
- HEFCE start-up funding
- Barts Cancer Centre pump-priming grant
Key Publications
pH regulation and beyond: unanticipated functions for the voltage-gated proton channel HVCN1.
Capasso M, DeCoursey TE, Dyer MJS.
Trends Cell Biol, 2011 Jan:21(1):20-8. Cover article. PMID: 20961760
HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species.
Capasso M, Bhamrah MK, Henley T, Boyd RS, Langlais C, Cain K, Dinsdale D, Pulford K, Khan M, Musset B, Cherny VV, Morgan D, Gascoyne RD, Vigorito E, DeCoursey TE, MacLennan IC, Dyer MJ.
Nat Immunol. 2010 Mar;11(3):265-72. PMID: 20139987
Identification of Thr29 as a critical phosphorylation site that activates the human proton channel Hvcn1 in leukocytes.
Musset B*, Capasso M*, Cherny VV, Morgan D, Bhamrah M, Dyer MJ, DeCoursey TE.
J Biol Chem. 2010 Feb 19;285(8):5117-21. PMID: 20037153
Voltage-gated proton channels maintain pH in human neutrophils during phagocytosis.
Morgan D, Capasso M, Musset B, Cherny VV, Ríos E, Dyer MJ, DeCoursey TE.
Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):18022-7. PMID: 19805063
Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Russell LJ*, Capasso M*, Vater I, Akasaka T, Bernard OA, Calasanz MJ, Chandrasekaran T, Chapiro E, Gesk S, Griffiths M, Guttery DS, Haferlach C, Harder L, Heidenreich O, Irving J, Kearney L, Nguyen-Khac F, Machado L, Minto L, Majid A, Moorman AV, Morrison H, Rand V, Strefford JC, Schwab C, Tönnies H, Dyer MJ, Siebert R, Harrison CJ. Blood. 2009 Sep 24;114(13):2688-98. PMID: 19641190
Further Publications
For additional publications, please click here.
Research Group
Ms Charulata Reddy, research technician.
