As part of our interview series, Meet the Scientists, we caught up with PhD student Freya Leif, who is at Leeds University working on a Breast Cancer UK funded research project looking at the role of nuclear receptors in breast cancer.

Why have you chosen to work as a scientific researcher, and what in particular drew you to breast cancer research? 

I studied Biotechnology with Enterprise at the University of Leeds for my undergraduate and Masters degrees. This was a broad subject, but I found I was particularly interested in understanding how diseases work on a molecular level and how drugs specifically target disease mechanisms.

Cancer is not one singular disease, there are so many different types that occur and behave in different ways. Even breast cancer has several different subtypes which can be classified in different ways by considering their characteristics and genetic profiles.

The more we understand how these different subtypes behave the better chance we have of identifying the most successful therapy for a given person. I find this really exciting and when I saw my PhD project advertised, I knew it was something I wanted to be involved in!

What is your research about? What are Nuclear Receptors?

Nuclear receptors are special proteins found in cells that respond to hormones and tell the cells what to do by activating DNA to switch genes on or off. This regulates the growth, activity, and death of cells.

A nuclear receptor lots of people have heard of is the estrogen receptor. The estrogen hormone is important for the normal growth and function of cells in the breast. However, disturbed regulation of oestrogen signalling can lead to cells growing in an uncontrolled way, resulting in cancer. There are drugs available that can stop estrogen binding to its receptor and this stops the growth signals to prevent cancer progression.

I work on triple negative breast cancer (TNBC) which is a rare but often aggressive type of breast cancer. It does not have the receptors for estrogen, progesterone or HER2. These receptors are the main targets for breast cancer therapy so people with TNBC are left with limited treatment options.

My project is investigating the glucocorticoid receptor (related to the estrogen receptor), to see how it behaves in TNBC and whether it could be a target for therapy. As part of this I have been working to create breast cancer spheroids or ‘mini tumours’ that we can use to test treatments on.

Why are Nuclear Receptors such an interesting research field?

Nuclear receptors are really interesting as they play an important role in determining which genes are activated in a cell and therefore how a cell behaves. If we can understand exactly how this works, we can then identify ways of targeting these mechanisms to prevent disease.

As well as this, currently around 13% of FDA approved drugs target nuclear receptors. This means if we can work out what a particular nuclear receptor is doing in a particular disease, we can potentially repurpose some of these drugs that are already available and have been through safety testing. This is much quicker and cheaper than developing new drugs completely from scratch!

When imagining a scientist at work, many people think of a person in a lab wearing a white coat – for this project you worked a lot with computers – Can you describe what you did?

Lots of researchers publish the data from their lab work online for anyone to use. We have looked at data from experiments using breast cancer cells treated with different things to see how gene expression changes. This allows us to predict how we think cancer cells behave and identify possible targets for therapy as well as predicting chemicals that might alter the way cells behave. We will then investigate these predictions in the lab to see if they are true.

What were your main findings?

We have found that the glucocorticoid receptor can promote growth in TNBC and I have been working lots on creating the spheroid (‘mini tumour’) model. This model is now ready to go so we can start testing how different treatments affect tumour growth. Our computer work has also identified a number of different things we think are important for growth in TNBC and now we are back in the lab we can start investigating these!

What previous discoveries led to your work?

The glucocorticoid receptor is an important regulator of inflammation and immunity and glucocorticoids (the molecules that bind to the receptor) are used to treat chronic inflammatory disorders and some types of cancer. In normal breast cells the glucocorticoid receptor is required for the correct timing of cell growth during breast development. The glucocorticoid receptor has also been observed in breast cancers, particularly more aggressive and invasive cancers. In TNBC high levels of the glucocorticoid receptor has been associated with a worse survival and this is what led us to investigate how it could be targeted for therapy.

What are the possible (real world) applications of your research findings?

We hope that better understanding the molecular mechanisms of breast cancer will identify new drug targets for people who have TNBC. This is really important as TNBC is often aggressive and treatments are more limited for this subtype. Also, if we can identify chemicals that alter the way cells behave resulting in cancer this can be used to prevent cancer cases in the future.

What’s next for you?

I’ve just started the third year of my PhD and having missed six months of lab time due to COVID disruptions it’s going to be a very busy in the lab! Then it’s on to writing up my results…

In terms of your career: What do you hope to be doing in five years’ time?

Honestly – I’m not sure yet!

What do you like to do when you’re not working?

I love travelling and exploring new places, I used some of my time in lockdown to practice my Spanish so I’d love to visit South America again once it’s safe! I also enjoy keeping fit and do lots of yoga and running. I should have been doing the Leeds half marathon and Tough Mudder this summer (fingers crossed for 2021), but I did manage to do a very rainy Yorkshire Three Peaks!

 

We’re thankful to Freya for taking the time to talk to us and to Dr Laura Matthews, lead researcher on the “The role of nuclear receptors in breast cancer”-project for their work to help prevent breast cancer.

This project and the other research projects we are funding are made possible by your generous donations.

If you would like to find out more about our scientific work, please see current research and past research.  If you would like to make a donation to support future projects, please donate today.

Together we can help future generations avoid the devastating impact a breast cancer diagnosis can have on a person’s life.


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