PhD Studentship: Combination of cellular and metabolic therapy for meningioma treatment

DoS Leandro José de Assis (leandro.deassis@plymouth.ac.uk)

2^nd Supervisor Jane Carré (jane.carre@plymouth.ac.uk)

3^rd Supervisor Oliver Hanemann (oliver.hanemann@plymouth.ac.uk)

4^th Supervisor Liyam Laraba (liyam.laraba@plymouth.ac.uk)

Applications are invited for a three-year PhD studentship, starting 01 October 2024 or 01 January 2025.

Project Description

Tumour progression requires a metabolic rewiring of cancer cells, providing enough energy for metabolism and cellular growth increasing the fitness of cancer cells for proliferation and survival1. Meningiomas are the most common brain tumours, classified by the World Health Organization (WHO) according to aggressiveness and recurrence as grade 1 (frequency 80-85%), 2 atypical (frequency 15-20%), and 3 anaplastic (frequency 1-2%)². There is a lack of effective systemic treatment for meningiomas, in part due to the absence of mechanistic targets. An observed rewiring in brain tumours is the modulation of metabolism, enhancing glucose uptake and usage of different energy sources such as lipids, amino acids, and lactate^3–5. Cancer cells with increased growth rates engage aerobic glycolysis where the metabolism of the glucose molecule is driven to lactate production, a phenomenon termed the Warburg Effect that is observed in several tumour tissues⁴.

Preliminary results in vivo showed that depletion of HK2 affects tumour growth. Furthermore, this project provided HK2-specific interactions (not present in non-tumour cells) for the design of peptides interfering with these interactions and affecting HK2 function providing a systemic treatment of meningioma. Intervention on specific targets interacting with HK2 and controlling the proliferation that relies on metabolic and/or cellular HK2-specific regulation could give more specificity and less toxicity in a possible clinical intervention. This proposal aims to characterize the regulation of HK2-specific interactions driving proliferation and aggressiveness in meningiomas. Furthermore, the proposal aims to study the development of peptides interfering with these interactions and affecting HK2 function specifically in meningiomas in vitro and in vivo. Training will be provided to develop knowledge and technical skills to enable the trainee to conduct high-quality and independent research.

References:

1. Scholtes, C. & Giguère, V. Transcriptional control of energy metabolism by nuclear receptors. Nat. Rev. Mol. Cell Biol. 23, (2022).
2. Buerki, R. A. et al. An overview of meningiomas. Futur. Oncol. 14, 2161–2177 (2018).
3. Faubert, B. et al. Lactate Metabolism in Human Lung Tumors. Cell 171, 358-371.e9 (2017).
4. Vander Heiden, M. G., Cantley, L. C. & Thompson, C. B. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science (80-. ). 324, 1029–1033 (2009).
5. Pathria, G. & Ronai, Z. A. Harnessing the Co-vulnerabilities of Amino Acid-Restricted Cancers. Cell Metab. 33, 9–20 (2021).

Eligibility

Applicants should have (at least) a first or upper-second-class honours degree in an appropriate subject and preferably a relevant MSc or MRes qualification.

The studentship is supported for 3 years and includes full Home/EU tuition fees plus a stipend of £18,655 per annum. The studentship will only fully fund those applicants who are eligible for Home/EU fees with relevant qualifications. Applicants normally required to cover overseas fees will have to cover the difference between the Home/EU and the overseas tuition fee rates.

To apply for this position please click the Apply button above.

Please clearly state the name of the studentship that you are applying for on the top of your personal statement.

The closing date for applications is 12 noon on 12^th August 2024.

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