Combination of cellular and metabolic therapy for meningioma treatment

Director of Studies (DoS): Dr Leandro José de Assis 

2nd Supervisor: Dr Jane Carré 

3rd Supervisor: Professor Oliver Hanemann 

4th Supervisor: Dr Liyam Laraba 

Applications are invited for a three-year PhD studentship. The studentship should start on 01 October 2024 or 01 January 2025.

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.

<sup>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).</sup>

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 three 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.

NB: The studentship is supported for three years of the four-year registration period. The fourth year is a self-funded ‘writing-up’ year.

If you wish to discuss this project further informally, please contact Dr Leandro José de Assis.

Please see our apply for a postgraduate research programme page for a list of supporting documents to upload with your application. 

For more information on the admissions process generally, please visit our apply for a postgraduate research programme page or contact the Doctoral College at research.degree.admissions@plymouth.ac.uk.

Shortlisted candidates will be invited for interview later in August. We regret that we may not be able to respond to all applications. Applicants who have not received an offer of a place should consider their application has been unsuccessful on this occasion.