The road to curing the incurable

Tell us about your academic journey… how did you come to be working in cancer research?

From a young age, I’ve been captivated by the inner workings of the world around me. This curiosity led me to pursue a degree in Neuroscience at the University of Nottingham. One of the most valuable experiences during my studies was spending a year abroad at the mental health research institute in Melbourne. This led me to later pursue a Ph.D. at Imperial College London where my work identified how diet and gut microbiota interact to shape the cellular composition of the gut and in turn influence appetite and body weight and solidified my passion for research.

The next couple of years were less smooth. I moved to San Francisco to take up a post-doctoral position at UCSF. However, within a year was back in England as my mum was diagnosed with cancer. During this time, I undertook an internship at Imperial Innovations – a great learning experience that allowed me the flexibility to stay with my mum when she needed help. However, whilst I loved my time at Imperial Innovations, it taught me that I needed to be back in the lab!

Influenced by my mum’s experience with cancer, I took on a postdoctoral position in 2017 with Professor Simona Parrinello at UCL to study the role of the microenvironment in brain tumours. Working with Simona for almost nine years now has been an incredible honour and has allowed me to grow as a researcher. After an initial postdoctoral position on a CRUK-funded project, I successfully applied for a CRUK RadNet research fellowship to remain in the Parrinello group and develop my independent research interests.

Looking to the future in 2025 I will be starting my own group at the University of Oxford to study the unique ways by which subpopulations of tumour cells resist current therapies. In doing so, I hope to pioneer novel sensitisation strategies that address tumour heterogeneity and plasticity with the ultimate goal of transforming glioblastoma from an incurable to a curable disease.

A lot of your current work is rooted in glioblastoma and the role the microenvironment plays in its development, tell us a little about that…

One of the pivotal moments early in my postdoc was when we first observed tumour cells mimicking normal cells – oligodendrocytes – in certain brain regions.

This work eventually led to the publication of a paper in 2021. Brain tumours have a strong tendency to invade white matter tracts, that connect different regions of the brain. As they do so, they injure the surrounding tissue. Such an injury can cause normal progenitor cells to differentiate in order to replace lost oligodendrocytes and regenerate white matter in response to injury. What we were observing was that tumour cells could respond in a similar manner, and whilst they did not produce white matter, this did cause them to stop dividing. Cancer is of course a disease of de-regulated proliferation, so identifying factors that stop cells from dividing opens potential treatment strategies.

By further understanding the mechanisms by which differentiation was being induced, we induced differentiation in an injury-independent manner to supress tumour growth and improve survival. This suggests regulating cell fate decisions could provide new treatment avenues for glioblastoma.

Do you think we’ll ever see an actual clinical intervention which aims to nudge tumour cell fate to become less aggressive?

While it is hard to predict, I wouldn’t pursue this avenue of research if I didn’t believe it was possible. One of my favourite quotes from David Deutsch’s book The Beginning of Infinity is, “Everything that is not forbidden by the laws of nature is achievable given the right knowledge.”

In recent years, it has become apparent that brain tumours exhibit pronounced plasticity. This means that simply nudging tumour cells towards a less aggressive state is unlikely to be curative. The answer, I believe, is to first understand the interplay between cell fate and current therapies. This understanding could enable us to nudge cells towards more treatment-sensitive states, potentially eradicating them completely.

However, before we can achieve this, we need to understand these biological processes at a fundamental level. By doing so, we open the door not only to clinical interventions that regulate cell fate but also to discovering new biological phenomena that may lead to innovative therapeutic strategies that we have yet to imagine.

So, I believe that clinical intervention based on regulating tumour cell fate is possible with the right knowledge, which we have yet to acquire. And in acquiring this knowledge, we may unveil new and unpredictable opportunities for improving cancer treatment.

You also work on the role of cell fate in shaping the response to radiotherapy – tell us about that…

In addition to understanding cell fate regulation, I am also interested in the unique ways subpopulations of cells resist therapies and identifying their vulnerabilities, which would enable us to develop new combination approaches.

For example, we are exploring how subpopulations of cells depend on different DNA repair processes following radiation. We believe this research will pave the way for treatment strategies that can sensitise even the most resistant cell states, bringing us closer to more effective cancer therapies.

How useful has it been to be connected to RadNet?

Being part of the Radiation Network has been immensely valuable, especially as someone who had no experience in the field of radiation prior to 2020. It has allowed me to build relationships that have led to productive collaborations, mentorships, and much-needed support systems.

For example, I have developed an important interdisciplinary collaboration with my good friend Jamie Dean, combining wet lab approaches with mathematical modelling to create projects beyond our individual capabilities. Additionally, RadNet has provided essential infrastructure, including access to irradiation platforms and supported the development of new research avenues through seed funding.