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60 seconds with David Clynes

David is a group leader who has been awarded with a 'Children with Cancer UK Paul O'Gorman Research Fellowship'.

 

In this interview, David gives us an insight into his current research on the ALT Pathway and explains how his lab hope to shed new light on strategies that can be used to understand and treat cancers that are currently incurable

 

Tell us a little about your research

My lab is interested in a particular hallmark of cancers, the ability of a cancer cell to maintain the length of its telomeres, which in turn allows the cell to proliferate indefinitely. It is now clear that there are at least two distinct pathways by which telomeres can be lengthened in cancer.

We research a relatively poorly understood pathway of telomere lengthening called the Alternative Lengthening of Telomeres or ‘ALT’. We now know the ALT pathway is effectively a result of aberrant DNA repair at telomeres. This allows us to touch on two areas of research; namely trying to understand how DNA is normally repaired at telomeres and how this is perturbed in these cancers and also how we might target ALT cancer cells for the development of novel cancer therapies.

Why does your research matter?

This work is important as many cancers that use the ALT pathway have an extremely poor prognosis and therefore we desperately need new approaches to treating these cancers. Many cancers of the central nervous system are ALT positive, including Glioblastoma Multiforme. Strikingly, this is particularly true in paediatric cases and hence my lab is funded through Children with Cancer UK where we hope to shed new light on strategies that can be used to understand and treat these currently incurable cancers.

What is the makeup of your lab?

I established my group just over a year ago and currently have five members composed of a Research Assistant, a D.Phil student and two MRes students and myself of course. 

How did you get to where you are today and what support have you particularly valued?

I was able to establish my group through successfully being awarded a career development fellowship. I think it is important, particularly during your post-doc years that you get support to develop your own ideas and become passionate about a research area. I was lucky in that my post-doctoral supervisors always supported me in doing this.

Research can be hard and daunting and it can sometimes be easy to become disheartened. I think the best advice I have been given is to never take things too personally (particularly when going through the peer review process). I think without taking this on board I wouldn’t be here today!

What’s one of the more interesting techniques you are using?

We are one of the few labs in the world that is set up to look for the markers of the ALT pathway which puts us is in a strong position to look into these cancers. Some of these techniques can be a little bit cumbersome/time consuming so a hope I have is that we can work on streamlining/simplifying them so they can one day be quickly used in clinic to stratify whether a cancer is ALT positive or not.

Like most biologists I believe the advent CRISPR/Cas9 based genome editing is the most exciting advance in the last few years. One cool technique we are currently trialling is the use of CRISPR (Cas13a) to target and degrade RNAs.

What’s a typical day like in the lab?

I guess there is no typical day really, which is one of the great things about research! I strongly believe that research shouldn’t be a solitary pursuit and as such I encourage my lab to share ideas and be open about their work, so we will have very interesting discussions on a daily basis. I find that breakthroughs and scientific ideas only really hit you when you discuss with others. You really need to enjoy your research and lab environment and then the hard work you undoubtedly need to be successful becomes easy!

How do you see your field developing in the next ten years?

Ten years is a long time to predict but I guess some big questions will still need addressing. In terms of cancer therapy, I think there are still great hurdles with drug delivery (particularly with cancers of the Central Nervous System). Also, we will need at some point to come to some kind of consensus as to how best to stratify cancers for treatment and predict outcome and response more accurately to certain therapies.  Time will tell if the ALT status of a given cancer will have a role to play in this.

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