Dr Fedor Berditchevski

• PhD Molecular Biology, 1988
• BSc/MSc Biochemistry, 1983

Fedor Berditchevski graduated from the Moscow State University in Russia where he studied virology and biochemistry. He obtained his PhD in molecular biology from the Engelhardt Institute of Molecular Biology of Russian Academy of Sciences. He undertook post-doctoral training in the laboratory of Professor Joyce Taylor-Papadimitriou at the Imperial Cancer Research Fund in London, followed by training in the laboratory of Professor Martin Hemler at the Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.

He was appointed as a Lecturer, subsequently, as a Senior Research Fellow and Reader in Cancer Cell Biology at the Cancer Research UK Institute for Cancer Studies, University of Birmingham. Fedor served on Scientific Advisory panels for the AICR and Breast Cancer Campaign. He is currently serving on the Scientific Advisory panel of the Breast Cancer Now.

• SGT lead, MBChB 2 Year - Cancer: Causes and Cures
• BMedSci Clinical Sciences Intercalated Course
• Deputy Lead, BMedSci 3^rd Year optional module – Cell Communication in Disease
• BMedSci 2^nd Year
• Personal Mentor for MBChB students

Supervising MRes and PhD students  

Research in Fedor’s lab is focused on the role of tetraspanin proteins in cancer. Tetraspanins are a large family of four-transmembrane domain proteins which are associated with one another and a number of other transmembrane and cytoplasmic proteins to form tetraspanin-enriched molecular aggregates that are often referred as to tetraspanin-enriched microdomains. Controlled lateral juxtaposition of various transmembrane and cytoplasmic proteins and coordination of their biochemical functions was proposed as the main molecular mechanism underlying a multitude of physiological activities ascribed to tetraspanin proteins.

Research themes

Tetraspanins and Immune Microenvironment in Inflammatory Breast Cancer

Inflammatory breast cancer (IBC) is a rare, clinically distinct subtype of locally advanced breast cancers (LABC) with poor prognosis and no effective therapies. We have recently carried out the first UK-wide audit of IBC cases and established that in spite of recent therapeutic advances, long-term survival of IBC patients is significantly lower when compared to all breast cancers (5-year survival rate for IBC patients is ~55%, as compared to 10-year survival of 78% for all breast cancers) (manuscript in preparation). The immune landscape in IBC is poorly defined. The overall purpose of the project is to carry out comprehensive characterisation of immune microenvironment in IBC and determine how tetraspanin-related molecular pathways control homing of various immune effector cells to cancerous tissues.

Tetraspanin microdomains in signalling via receptor tyrosine kinases

ErbB receptors include four monomeric receptor tyrosine kinases (i.e. EGFR/ErbB1, ErbB2/Her2, ErbB3 and ErbB4), which are activated by soluble and membrane-acnored ligands. Ligand binding induces homo- and heterodimerization of the receptors leading to phosphorylation of their cytoplasmic regions at multiple tyrosine residues, assembly of a variety signalling complexes and activation of signalling networks that control a range of cellular processed including proliferation, differentiation, migration and apoptosis.

We investigate the involvement of various tetraspanin proteins and their non-tetraspanin partners in various aspects of signalling via ErbB receptors including processing and secretion of ligands for ErbB proteins, ligand-induced ubiquitylation and phosphorylation of the receptors, mechanisms underlying stability of the receptors in cancerous cells.

The role of syntenin-tetraspanin complexes in trafficking

Syntenin-1 is a PDZ domain containing adaptor protein with well established roles in cell proliferation and migration. Syntenin-1 also regulates various aspects of endocytic trafficking including endocytosis, recycling and recruitment of proteins to exosomes. We have reported that syntenin-1 is associated with tetraspanin microdomains where it can physically link tetraspanins with non-tetraspanin transmembrane partners. In addition, syntenin-1 is associated with ubiquitylated cytoplasmic proteins and these interactions are controlled by Ulk1, a serine-threonine kinase which plays a critical role in autophagy.  Our current work is focused on characterisation of biological and structural aspects of novel ubiquitin-based interactions involving syntenin-1.

Fedor is an academic lead of the inflammatory breast cancer initiative in the UK.