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Unravelling inherited kidney diseases: an International Women’s Day conversation with Dr Melanie Chan

06 March 2024

For International Women’s Day, we sat down with Dr Melanie Chan from Imperial College London, a dedicated and passionate kidney doctor, researcher, and mum of two, to discuss her fascinating work unravelling the causes of inherited kidney diseases, and her advice for women and girls aspiring to a similar career path.

We are proud to have supported Melanie through a Kidney Research UK clinical training fellowship (an award that allows medical doctors to gain specialised training in kidney research) from 2017 to 2022, where she uncovered some key insights into the causes of posterior urethral valves (PUV), a condition where baby boys are born with a thin piece of tissue blocking the exit of their bladder, often leading to serious kidney damage.  

Dr Melanie Chan
Dr Melanie Chan

Can you tell us a bit about your career background and what inspired you to pursue a career and kidney research? 

My first introduction to research was working in a lab at medical school which I really enjoyed. I was fascinated by exploring the reasons why people get diseases and thinking about how they could be treated. When I was a junior doctor, I I worked with kidney patients, and I found the range of conditions that affect people with kidney problems so interesting. The close relationships that form between kidney patients and their medical team over many years was also a key reason why I chose kidney medicine. 

During my training, I really got interested in families that were affected with inherited kidney diseases and so I did a course in genomic medicine - learning about how DNA can be used to diagnose diseases and to inform treatments. DNA is our genetic code and contains all the instructions for making you, you. 

I was fortunate that when I was looking for research projects it was at a time when there was this revolution in genomic medicine. There was so much data coming out from people with rare kidney diseases who had undergone something called whole genome sequencing. This means that they had had all of their genome or DNA read, and we wanted to try and pinpoint changes in the DNA which might explain their disease. The beauty of being able to do this in large groups of patients is that we didn't necessarily need to have a clear target before we looked in the DNA so we could look for previously unknown causes. 

I did my PhD funded by Kidney Research UK with Professor Danny Gale at University College London, who was the most fantastic mentor, and this really transformed my career. I learnt so much during the fellowship: how to analyse DNA, perform different statistical genetics analysis and look at large data sets. My research was all ‘dry lab’, which means it's all computer based. Before this, I had always imagined research as being in a lab holding a pipette, and so doing this PhD just opened up a whole new world to me of this other side of research and the value of looking at large datasets to gain insights into disease.  

Throughout my training I realised that I absolutely love research. It's amazing being able to see patients in the clinic with inherited kidney diseases, and then be able to look at their DNA and try to figure out exactly what is causing the problem, and then hopefully identify new treatments to help these patients in the future.

Can you tell us about what you were working on during your fellowship, and what you discovered? 

I was looking specifically at a group of patients who were born with kidneys and bladders that don't form properly in the womb. We know that this is the most common cause of kidney disease and kidney failure in children and young people, but it's traditionally been quite an under-researched area of kidney medicine. 

I took a large cohort of patients with these kidney and bladder malformations, and I looked for differences between the DNA of patients who have these conditions and those who don’t. One of the conditions I focussed on was PUV, a rare condition that only affects boys, who in many cases develop kidney failure and need a kidney transplant or dialysis, and they often have bladder problems too. 

It's a serious condition and we never really knew what caused it. When I compared the DNA of patients with and without PUV, I found two bits of the genome where there was a difference. One impacted a gene for a transcription factor - these are essentially switches that turn genes on or off at the right time - called TBX5, and we found that this specific switch was potentially quite important for PUV. We then found another gene called PTK7, which is involved in the way tubes – like the developing spinal cord or urethra – are made during development. This has, for the first time, given us an insight into what might be going wrong in the womb to cause PUV. We now need to do further research to investigate exactly what's going on in these two bits of the genome. 

What will the next steps in your research be? 

At the moment, I am using some of the newer techniques that are now available to look at how different genes are switched on and off during development. I'm looking early in the development of the kidneys and the bladder to try and understand exactly how the DNA changes that I've found might be impacting the way genes are activated in various cells. Once we've got a better view of that, then we would want to take that into potential organoid (mini organs in a dish) models, to see what happens.  

Can you explain a bit about the impact of the Kidney Research UK fellowship on your career? 

It's given me the opportunity to learn some amazing skills and the time to really develop my interest in inherited kidney disease and genetics. It's meant that I could work with and meet some amazing people, including my PhD supervisor Danny, who have been instrumental in giving me the confidence to believe that I can do this as a career. Kidney Research UK too has been super supportive throughout my fellowship, and I will be forever grateful that they decided to fund my project. As a result of the work I did during my fellowship I also received an award from the UK Kidney Association which was a real honour. I'm now hoping to become more independent as a researcher and really expand my research, particularly into kidney and bladder problems that people are born with. 

 

What advice would you give to young girls or women who are interested in pursuing a career in either medicine or research or both?  

I would say find something that you are passionate about and that you love doing. From a research point of view, you are often working towards very long-term goals, and you don't always see an immediate reward or output, so you need to enjoy the journey.  

Find a mentor who will support you. I've been lucky to have an amazing mentor who has been really supportive, pushed and promoted me, and has been instrumental in me pursuing a career in clinical academic medicine.  

Role models are also key. As a clinical academic coming through training, when you look up you want to see other women who have done it and been successful. I think there is still a lot to be done to encourage women to stay in academic medicine. It’s getting much better but it's still so important to find a role model who can support you and guide you.

I also want to add that I have two kids and did most of my clinical training and PhD part-time. It might take a lot longer, but it is definitely possible to combine academia and clinical work, with family responsibilities.

It’s a really amazing and varied career - you get to combine both the medical aspect where you interact with patients and understand the key challenges and problems that they are dealing with, but at the same time can take a step back and think about the bigger picture on the research side. It’s a unique opportunity and I am so lucky to enjoy my job. 

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