Marie Curie Fellows

Named after the double Nobel Prize winning Polish-French scientist famed for her work on radioactivity, and supporting researchers at all stages of their careers, irrespective of nationality. All VAMPIRE fellows are registered for a PhD at the University of Birmingham.

After a very careful recruitment process our current researchers were selected from around Europe. They have received preliminary training fundamental for the optimal implementation of their training. Three researchers are in Birmingham while two are currently in the Netherlands working on their research projects at Somantix. They will be exposed to local training activities performed at each site. Regular joint research meetings between the two groups are held via Skype. Throughout the entire project, network-wide training activities are held with the purpose of bringing coherence to the VAMPIRE programme and providing fellows with common knowledge of both scientific topics and transferable skills.

 

Fellows

croic-marta

Marta Coric (Croatia)
Email: m.coric@bham.ac.uk

My main project is to identify the role(s) of novel tumour endothelial marker CLEC14A identified by our group in the University of Birmingham. It is an endothelial specific member of C-type lectin domain protein family. This protein is found to be highly expressed in tumour vasculature of a wide range of different tumours, but was found absent, or lowly expressed in the adjacent healthy tissue. This poses a good target for potential anticancer therapies. Nevertheless more information is needed to create a smart and good way to target this protein in cancer. In the first part of my project I will identify binding partners of intracellular domain of CLEC14A with the help of mass spectrometry, and validate these findings with different techniques. The results will provide a starting point for hypothetical cell processes in which CLEC14A can be involved and open a window for further investigation. The second part of my project is imaging of cells transfected with CLEC14A and CLEC14A with deleted intracellular domain to investigate potential changes in morphology or functions of these cells, as well as monitoring co-localisation of CLEC14A and different proteins form the mass spectrometry results.

ebell-katharina       

Katharina Ebell (Germany)
Based in Netherlands
E-mail: k.ebell@bham.ac.uk

My project focuses on the identification of novel markers for tumor vasculature in colorectal cancer. In particular I am trying to identify ligands that are specifically secreted by tumor endothelial cells. Different genes were identified in a screening using tumor microarrays and target validation will be done using various in-vitro angiogenesis assays. After validation these proteins can then be used to specifically target tumor vasculature by monoclonal antibodies or small molecules. Targeting tumor vasculature can be more promising than targeting tumor cells directly because the endothelial cells remain non-transformed and it is therefore less likely that a drug-resistance is developed.

Additionally to the identification of new targets I am also working on the characterization of the interaction of CLEC14A, a highly specific endothelial tumor cell marker identified by our group, with MMRN2, an extracellular matrix glycoprotein that is associated with tumor angiogenesis. Both proteins are known to interact with each other but the exact mechanism of this interaction remains elusive.

korzystka-aleksandra       

Aleksandra Korzystka (Poland)
Based in Netherlands
E-mail: a.korzsystka@bham.ac.uk

SomantiX B.V. and University of Birmingham have identified new potential tumor vasculature markers from CRC endothelium. The major goal of my project focuses on the selection of novel targets for tumor vasculature targeting, in particular transmembrane proteins. This approach increases a therapeutic specificity and may help to overcome the development of the drug-resistance, often observed in cancer treatment. Therefore, the most promising targets will be validated in model cells using various techniques, ex. in vitro angiogenesis assays. Moreover, their angiogenic role and tumor specificity will be investigated using different functional assays. In parallel, the research will be conducted on several validated targets. The second part of my project concerns the generation and selection of small antibodies against our candidates that finally will be used to investigate and identify therapeutic targeting applications in vitro and in vivo.

lasota-jagoda     

Jagoda Lasota (Poland)
E-mail: j.lasota@bham.ac.uk

Recently our group has found a set of transmembrane proteins, expressed exclusively on lung cancer vessels. Such an identification of potential tumour markers is followed by a multistep procedure of validation. It means to define the localization in the cell or tissues, its distribution within cell compartments or functional analyses to discover the target’s role. My main task is to visualize the localization of previously identified targets’ mRNA in highly vascularized lung tumour tissues, with the use of a powerful technique of fluorescent in-situ hybridization. This will give us a precious information not only where the marker is localized, but also how abundantly it is expressed.

mabretti-marco       

Marco Mambretti (Italy)
E-mail: m.mambretti@bham.ac.uk

My project is divided into 2 parts. The first part comprehends the production of antibody raised against the extracellular portion of CLEC14A, which has been previously defined by Bicknell’s lab as a good tumor endothelial marker. This will be carried out using two different approaches. One is the canonical production of antibodies by immunization of the mice and the other will take advantage of the ETH2-GOLD phage library, which will be used doing phage display onto the specific purified antigen. Both of these approaches will run in parallel and will applied later to other promising targets.
The second part of my project is based on the validation of possible new tumor endothelial markers in colorectal cancer and in renal cell carcinoma. This will be done defining the expression pattern in patient samples via qPCR (comparing normal endothelium, tumor endothelium, the tumor bulk and healthy tissue). If the expression pattern will look promising, the validation will be carried out in a in vitro settings performing different angiogenesis assays.