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Involvement of the matrix protein SPARC in the dynamic interaction between tumour and host cells

Tumour growth depends on the crosstalk between malignant and surrounding stromal cells (fibroblasts, osteoblasts, endothelial cells and inflammatory cells). Malignant cells secrete soluble proteins that reach neighbouring stromal cells, forcing them to provide a suitable 3D environment for their growth and spreading (metastasis). Different studies, including expression array analysis, identified the matrix protein SPARC as a marker of poor prognosis in different types of cancer.

Growth factors, like TGFbeta and PTHrP, play a role in tumour progression by modulating protein expression. However, little is known of how these external factors modulate the intracellular trafficking machinery to stimulate secretion of proteins such as SPARC.

The main aim of the project is to elucidate how aberrant growth factor signalling alters protein secretion. To investigate the effects of TGFbeta and PTHrP on SPARC secretion, we plan to use tumour cells and primary osteoblastic cells known to naturally express SPARC. We will study secretion of endogenous SPARC by immunoprecipitation as well as by measuring secretion of Green Fluorescent Protein-SPARC chimerae in response to treatment with TGFbeta and PTHrP. TGFbeta and PTHrP signalling most likely stimulates GTP exchange factors (GEF) that are specific for the small GTPases  of the ARF and Rab family. We will therefore study SPARC secretion before and after knockdown of selected GTP-exchange proteins with small interfering RNA.

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This is a self funded topic

Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.

Dr Gudrun Stenbeck - Qualifications: -
  • 1993: PhD in Chemical Technology/Biochemistry, Technical University Darmstadt, Germany
  • 1989: German equivalent of BS/MS degree in Chemical Technology, Technical University Darmstadt, Germany

Dr Emmanouil Karteris - Dr Manos Karteris graduated with a BSc (Hons) in Medical Biochemistry from the University of Surrey in 1995. He then was awarded an MSc with Distinction in Medical Genetics with Immunology from Brunel University London in 1996 and completed his PhD in Molecular Endocrinology from the University of Warwick in 2000. He then undertook post-doctoral appointments at the University of Warwick, including a prestigious VIP Research Fellowship from the Wellcome Trust. He was appointed as Lecturer in Endocrinology at the University of Warwick from 2005-2006 and then he transferred to Brunel University London as a Lecturer in Biomedical Sciences in June 2006. In October 2017 Dr Karteris became a Senior Lecturer in the Division of Biomedical Sciences. He is also the head of the Cancer Biomarkers and Cellular Endocrinology Lab (CBCEL). For more information please visit the lab webpage: www.cbcel.org Qualifications: - BSc Medical Biochemistry, University of Surrey MSc Medical Genetics with Immunology, Brunel University PhD Molecular Endocrinology, University of Warwick PGCert HE & PGCERT IP Law, Brunel University