Dr Eugene Tulchinsky

Contact detailsEugene Tulchinsky

  • Tel: 0116 252 3223
  • Fax: 0116 252 3223
  • Office: Room 317, 3rd Floor, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, PO BOX 65, Leicester LE2 7LX

Personal details

  • MSc, Biochemistry - Moscow State University
  • PhD, Molecular Biology - Institute of Molecular Biology, Moscow

Websites

Publications

Selected publications from 2005

Research

Epithelial mesenchymal transition (EMT) is generation of motile and invasive mesenchymal cells from epithelial tissues. EMT is controlled by several embryonic transcription factors, ETFs, (or EMT-TFs) TWIST1, TWIST2, SNAIL1, SNAIL2, ZEB1, ZEB2, etc., which are implicated in different steps of embryonic development, wound-healing, fibrosis and cancer. We and others have demonstrated that ETFs play multiple roles in different types of human cancer, including carcinoma, melanoma, glioblastoma and haematological malignancies. They promote tumourigenicity, affect cell cycle control, apoptotic response, DNA repair and stemness.

These functions of ETFs are independent of their ability to induce EMT, but contribute to drug resistance and genomic instability. The EMT-independent functions of these transcription factors are in the focus of my research.

Activation ETFs occurs in response to mutational activation of signal transduction pathways in cancer cells or by microenviromental cues (Hill et al., 2013; Fig. 1). Our data indicate that ETFs alter cellular response to DNA damage and may sensitize tumours to different DNA repair and checkpoint inhibitors through synthetic lethality mechanisms. These approaches are of prime interest of precision medicine.

Figure 1

EMT and MET

My research interests are in the area of the interaction between EMT and other critical pathways in cancer cells. Cooperation between EMT and classical oncogenes results in oncogenic transformation, affects cell proliferation, stem cell-like features, DNA damage response, senescence and cell death. We believe that EMT programs determine such important cancer properties as altered sensitivity of disseminating cancers to different therapies or a phenomenon of dormant metastasis (Fig 1).

 

Figure 1
Fig. 1. A simplified scheme depicting multiple roles of EMT-TFs in human cancer (Browne et al., 2010, Cell Cycle 9, 886)

Reversibility is an important feature of EMT. In metastatic carcinomas, mesenchymal epithelial transition (MET) is required to re-establish epithelial structure of metastases. We revealed reversible switches in the expression of EMT-TFs in malignant melanoma. These switches are induced by melanoma-initiating mutations and orchestrated by an AP1 family member, FOS-related antigen 1 (FRA1). EMT-TFs switches resemble EMT and MET pathways in carcinoma cells. They represent a key determinant of tumour cell plasticity, one of key factors of drug resistance in cancer. (Figure 2) Further studies on the mechanisms regulating EMT/MET equilibrium in carcinomas and EMT-TF reprogramming in non-epithelial tumours is important for the development of new therapeutic approaches.

 

Figure 2
Fig. 2. A scheme illustrating MEK-ERK-FRA1-regulated EMT-TFs switches during melanomagenesis. These reversible switches impact on the expression of the master regulator of melanocytic lineage, MITF. This pathway regulates phenotypic plasticity in malignant melanoma (Tulchinsky et al., 2014, Oncotarget 5, 1)

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NEWS

SEND Study Success

Congratulations to Chris Avery, Honorary Associate Professor and Consultant Maxillofacial Surgeon, who with collaborating colleagues published the findings of the significant SEND study, a multi-centre randomised trial using two different surgical protocols for  mouth cancer treatment.  A nationwide first for this type of trial, using real-world data.  The paper, published in the British Journal of Cancer, is available by clicking this link: SEND Paper

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Congratulations from the LCRC to Bethan Rogoyski and Aleksandra Bzura.

Bethan won best oral presentation at the AMS Midlands Academy of Medical Sciences Festival held on 27th March 2019 for her presentation on "Redeployment: The potential of repurposed drugs in preventing mesothelioma".

Aleks won the University PGR poster fair competition on 18th March 2019 for her poster entitled "New hope for treating mesothelioma cancer using PARP inhibitors".

Also, a huge well done to Grandezza Aburido who was in the semi-finals of the PGR poster fair.

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New: Wellcome Trust Institutional Strategic Support Fund

Details

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Centre Health and Wellbeing Group
Join up for a walk on the park Friday lunchtime - details here.

More information from Jenny McNair jm65@le.ac.uk

Contact Details

Leicester Cancer Research Centre
Clinical Sciences Building
University of Leicester
Leicester Royal Infirmary
Leicester LE2 7LX

T: +44 (0) 116 252 3170
E: cancerstudies@le.ac.uk

(Please note this email address should not be used for clinical referrals or patient correspondence)

Maps and Directions

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Accessibility

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The University of Leicester is committed to equal access to our facilities. DisabledGo has a detailed accessibility guide for the Robert Kilpatrick Clinical Sciences Building.

Seminars

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