Viros-MB-PhD-006 – Brain ageing and melanoma brain metastasis

Closing date: 03/02/2023

MB-PhD Project: Brain ageing and melanoma brain metastasis

Lead Supervisor: Dr Amaya Viros Usandizaga
Email:amaya.viros@cruk.manchester.ac.uk
Co-Supervisors:
Prof Caroline Dive, Prof Frederico Roncaroli

Initial Intercalation Deadline: 12 December 2022

MB-PhD start date: September 2023
Interviews:
Tuesday 7 March 2023
Project Keywords: Melanoma, tumour microenvironment, metabolism
Research Opportunity: Intercalated PhD, leading to the award of PhD and MBChB

Applications for this project are now open. Candidates must contact prospective supervisor/s ahead of submitting an application. See the MB-PhD programme page for details of how to apply. 

 

Project Outline

Genomic evolution studies show that primary melanoma in the skin metastasises in parallel to multiple anatomic sites early in the course of disease. Metastatic melanoma at different anatomic sties has a heterogeneous behaviour, and critically, heterogenous response to therapy. Moreover, the metastatic destiny of melanoma cells differs by age. Brain metastases are more common (but not exclusive) in younger patients, and arise with a long time to progression from primary diagnosis.

We have preliminary data describing the TME cues that imprint specific metabolic melanoma cell states in the primary tumours. These states are permissive of melanoma brain metastases (MBM). Melanoma cells that arrive in the brain and form brain metastases (MBM) are defined by a high OXPHOS metabolism and are coupled to a highly invasive phenotype that destroys tissue locally and leads to high mortality due to local symptoms and complications. The rates of response to immunotherapy in the brain are low, primarily due to the reduced immune cancer fighting milieu that is characteristic of the brain TME.

This project will study how astrocytes interact and support melanoma cells as they extravasate from blood vessels, seed, grow in the brain and how this process varies in the aged and young brain. We will study how melanoma cells adapt to the brain secondary tumour microenvironment. We will study the local tissue factors (astrocytes) that increase melanoma metastatic adaptation in the young brain, explaining the observed increased seeding, growth and invasion in young brains compared to aged brains. Furthermore, we will use orthotopic in vivo models and human tissue to dissect immunotherapy MBM responses by age.

 

About the Viros Lab

The aim of the Skin Cancer and Ageing lab is to discover the biology driving poor outcome in aged skin cancer patients. We hope to discover new targets that can be taken forward in clinical translation to improve the lives of aged patients.

 

Supervisory Style

My aim would be to supervise a motivated and focused individual who wants to learn, thinks flexibly, adapts to the team and wishes to contribute to the publication aims of the lab. Independent work and reading is key to a successful PhD in the lab as students are expected to understand the rationale of the scientific question, read around the clinical aspect and methodology, keep up with competing scientific publications and hold regular one-on-one meetings with the supervisors and together with the SCA team to show results and contribute to the strategy of the project. The supervisors will provide mentorship, career guidance throughout the project and support the student’s wellbeing.

 

Lab Culture

My goal is to engage motivated scientists and clinician scientists in important scientific questions, using cutting edge methodology to deliver novel approaches to help aged patients. In my lab we have a collaborative spirit and have common and individual goals.

All individuals have their well-defined projects, however there is great scope to support and expand your training (and publication deliverables, scope of training) across other projects, as we are a small lab sharing multiple technology platforms, clinical data and samples. We have weekly or fortnightly all-group meetings and I have an open door/zoom policy every day.

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Get in Touch

Contact Simon Reeds, Postgraduate Programme Manager who manages the MB-PhD Programme.