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Fundamental immunosuppressive pathway determining ability of cancer and embryonic cells to escape cytotoxic immune attack

  • Full or part time
  • Application Deadline
    Monday, April 15, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

This project focuses on a fundamental breakthrough in the conceptual understanding of the Biochemistry of a process of malignant transformation. We discovered that blood cancer cells possess a unique molecular pathway that allows these cells to escape anti-cancer immunity (Gonçalves Silva et al. EBioMedicine 2017; Yasinska et al. Nanoscale 2018; Sakhnevych et al. Cell Mol Immunol 2018). Thus, the patient’s immune system becomes unable to kill malignant cells leading to disease progression. This pathway leads to secretion of the protein called galectin-9 that disables human cytotoxic lymphoid cells which are naturally capable of attacking/killing cancer cells. Our further experiments demonstrated that this pathway is also active in various solid tumour cells. The same situation was applicable to human embryonic cells. It is known that human body treats the embryo in a similar way to the tumour in the first stage of pregnancy. It is, thus, important that the rejection of the embryo is avoided.

This PhD project will focus on understanding molecular mechanisms underlying the regulation of this "anti-immune" pathway in order to be able to correct it pharmacologically. Importantly, uncovering the biochemistry of this pathway will be a game-changing concept in our understanding of malignant transformation.

The two work packages of the project will include: 1) Comparative investigation of biochemistry of the galectin-9 producing pathway in human embryonic and malignant cells. 2) Pharmacological correction of this pathway in malignant and embryonic human cells using highly specific peptides. This, on one hand, will enable the human immune system to remove cancer cells. On the other hand, it will help to prevent miscarriage caused by embryo rejection by the human immune system.

This project is a part of a collaborative interdisciplinary research programme including collaborators from the University Hospital Bern (Inselspital), Switzerland (Prof Fasler-Kan and Prof Berger), Diamond Light Source, Didcot, UK (Dr Hussain) and Aptum Biologics Ltd, Southampton, UK.

The candidate is expected to have a BSc or MSc Degree in Biochemistry, Immunology, Physiology or Cell/Molecular Biology.

Basic research/laboratory experience is essential.

To apply for this position please send your CV, letter of motivation and the names/addresses of potential references to Dr Vadim Sumbayev ().

The information about our research group can be found at: http://www.msp.ac.uk/about/staff/biological/sumbayev_vadim.html

Funding Notes

The PhD project is funded by the University of Kent Vice-Chancellor Scholarship

References

1. Sakhnevych SS, Yasinska IM, Bratt AM, Benlaouer O, Gonçalves Silva I, Hussain R, Siligardi G, Fiedler W, Wellbrock J, Gibbs BF, Ushkaryov YA, Sumbayev VV. Cortisol facilitates the immune escape of human acute myeloid leukemia cells by inducing latrophilin 1 expression. (2018) Cell Mol Immunol, 15, 994-997.

2. Yasinska IM, Gonzalves Silva I, Sakhnevych SS, Ruegg L, Hussain R, Siligardi G, Fiedler W, Wellbrock J, Bardelli M, Varani L, Raap U, Berger S, Gibbs BF, Fasler-Kan E, Sumbayev VV. High mobility group box 1 (HMGB1) acts as an “alarmin” to promote acute myeloid leukaemia progression. (2018) OncoImmunology, 7(6): e1438109.

3. Yasinska IM, Ceccone G, Ojea-Jimenes I, Ponti J, Hussain R, Siligardi G, Berger S, Fasler-Kan E, Bardelli M, Varani L., Fiedler W, Wellbrock J, Raap U, Gibbs BF, Calzolai L, Sumbayev VV. Highly specific targeting of human acute myeloid leukaemia cells using pharmacologically active nanoconjugates. (2018) Nanoscale, 10: 5827-5833.

4. Gonçalves Silva I, Yasinska IM, Sakhnevych SS, Fiedler W, Wellbrock J, Bardelli M, Varani L, Hussain R, Siligardi G, Ceccone G, Berger SM, Ushkaryov YA, Gibbs BF, Fasler-Kan E, Sumbayev VV. The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells. (2017) EBioMedicine, 22: 44-57.

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