Exploring the role of BK virus in kidney transplant patients’ cancer risk: a World Cancer Day conversation with Dr Simon Baker
For World Cancer Day 2024, we sat down with our researcher Dr Simon Baker from the University of York to discuss his important work focusing on understanding why kidney transplant patients face an increased risk of developing bladder cancer. His investigations centre around BK virus. BK virus is a common childhood infection that remains inactive in the kidneys throughout adult life but can be reactivated and cause problems in kidney transplant patients due to the medication used to stop transplant rejection.
A Q&A with Dr Simon Baker
We are proud to be supporting Simon through a fellowship grant to understand whether BK virus causes changes to the cells of the bladder that lead to cancer. Secondly with a PhD studentship where he will employ a student to find new targets for the treatment of BK virus in patients with a kidney transplant.
Q. Can you give us a little overview of your career background?
I’ve been working at the University of York since I did my biology undergraduate degree. I then went straight on to do my PhD, which was with a professor who specialised in the way that bladder cells work and how they develop their functions and protect themselves against urine, which is quite a toxic environment.
She was very much focused on developing accurate models in the lab. When we isolate cells from patients to grow in the lab, they often change how they behave, and she developed systems to maintain the specific functions of the cells and recreate their behaviour in the body. This work has underpinned my ability now to study infections and how cancers might start, because in order to study how a cancer starts, you need a really good model of the normal tissue.
Q. Can you give us a brief overview of your Kidney Research UK-funded work on the link between the BK virus and bladder cancer in kidney transplant patients?
Kidney transplant recipients are at around a three-fold greater risk of developing bladder cancer. For a long time, we didn't really understand why. Initially we thought that the reason for this increased risk was because the immunosuppressive drugs that patients take after transplant stop the immune system from sweeping up cancer cells. But this doesn’t explain why patients with kidney transplants have a higher risk of developing bladder cancers than other types of cancer. This led researchers to wonder whether there was something specific going on in the bladder.
We know that BK virus infection is one of the leading causes of kidney transplant loss. It is well known that the virus poses a risk to the kidney itself, but what was less well known was that it seems to also cause problems for the bladder. What we have started to show in our lab models is that BK virus does very specific kinds of damage to the cells that line the bladder. This can lead to changes in DNA that mirror the changes that we see in the DNA of patients with bladder cancer. This part of our research hasn’t been published yet, so we still need to be cautious about our results until they have been peer-reviewed, but we’re very optimistic about their potential.
We think that when BK virus infects the lining of the bladder, the cells fight back using special proteins. And whilst the cells are using these proteins to try and damage the viral DNA, sometimes they inadvertently damage their own DNA. When we have studied the DNA of the human cells in our lab models fighting the viral infection, we have seen patterns of DNA damage that look exactly like what we see in a bladder cancer sample, and that’s the first time that anyone's been able to reproduce that damage. For us, this strongly suggests a link between BK virus and the mutations that lead to bladder cancers. This means we need to re-evaluate how smoking increases the risk of bladder cancer.
Q. Why is BK virus a particular problem for kidney transplant patients?
Although with any type of transplant, patients need to take immunosuppressant drugs, BK infections seem to be more common in people who have had a kidney transplant. We’re not sure why yet. It seems the virus comes in on the transplanted kidney, and there might be situations where there are mismatches in the type of virus that the donor and recipient have been exposed to.
BK seems to cause the biggest problems in patients who have never had BK virus themselves but receive a kidney from someone who has, so their first exposure to BK virus happens when their immune system is suppressed. There’s also a possibility that there are different variants associated with the disease. There might be a mismatch between the type that you were exposed to as a child and the type that is carried in on your new kidney and there is research going on in other groups to look at that.
Q. Can you tell us a little about your new PhD project looking at ways to tackle BK infection?
In the kidney transplant field, there was already a desperate need for BK virus-specific medications, and now our work is supporting our theory that BK virus is also linked to bladder cancer, this need is even greater.
Most research is done in cancer cell lines or other actively growing cells, which divide very quickly and that makes it easy for BK virus to infect and kill them very quickly. This means researchers can only study a very short-term infection. In our unique lab models of the lining of the bladder, the cells are not dividing and that's important as that's the way the cells behave in the body. In our models, it takes a couple of months for the infection to start killing the tissue, so it's more like an infection in a patient and there is much more time for the cells to develop ways to fight back that we might be able to enhance.
This PhD studentship is trying to see if there is something that we've missed. We've been researching BK virus since the 1970s, but nobody has found a specific therapy. We think the reason for that might be that if you don't have a good model of the human cells, then you can't really understand what the virus is doing. That's what we're trying to change with this PhD studentship. We're looking for a new therapy that can exploit that new understanding.
Q. How might your research change the way we monitor and treat kidney patients?
We’re looking to improve our understanding of the risk that BK virus poses. We already know that it poses a big threat to transplanted kidneys, but if it also increases the chance of bladder cancer then we hope that knowing about these additional risks will make people take BK seriously.
There is currently no nationally agreed screening program for BK virus. So with the British Transplant Society, I'm co-chairing the development of new clinical guidelines for BK virus, with the hope that we could agree a national approach to screening where we could collect data from the whole country and bring it all together to really understand how much of a risk BK is posing to patients. At the moment, every centre has developed its own screening program, and some don't do any screening at all. We're trying get everyone in the UK to work together, with the hope that we can improve clinical practice.
Then the main goal of the PhD studentship is to find a new treatment that would nicely slot in. At the moment, if you've had a kidney transplant and you get a BK diagnosis, the clinical team will reduce your anti-rejection medication slightly and that allows the immune system to come back and fight the virus. And the idea is to get the anti-rejection medication just right so that it allows enough immune system function to kill the virus but not enough to reject the transplanted kidney.
What we hope is that we could add in a targeted therapy that really hits the virus at that time, so the little bit of immune system that we’re allowing back in stands a better chance of killing the virus.
Q. How do you involve kidney transplant patients in the research process, and how might their experiences contribute to the study's outcomes?
Patient involvement is extremely important in our work. We have patients on the panel for the British Transplantation Society clinical guidelines and I have worked with patients to write a patient information leaflet for people who have been diagnosed with BK after a kidney transplant.
I also share my research through the rare diseases networks. We talk about our research there and discuss whether we're focusing on the right things and have our priorities right. That's one of the things that led to the PhD student focusing on the treatments because when you talk to patients. The main worry they have is that it's terrifying to have your anti-rejection medicines reduced and to have that threat of rejection. It can cause psychological stress and it would be really empowering to have a specific therapy to target the virus and to try to treat it.
Q. What excites you the most about the potential impact of your work?
If we're right that the fight between the cells of the bladder and BK virus really causes the DNA damage that leads to bladder cancer, then what we've discovered is that bladder cancer is actually probably preventable in this patient group. It would then bear similarities to cervical cancer, that we can basically eradicate now with HPV vaccination.
It's possible that if we're right, and BK really does cause the majority of bladder cancers, then either vaccination or antiviral therapy at the right time in people's lives could mean that bladder cancer is preventable. That is a really exciting shift in the way we are thinking about this disease.
Around 5,000 people in the UK die every year from bladder cancer. If we could establish that the disease is actually preventable and change clinical practice to get in early and stop it from happening, that would be massive.
We would like to thank Simon for taking the time to chat to us about his impactful research and we look forward to keeping you updated on his progress!
Have you been diagnosed with kidney disease?
Request your free Kidney Kit today.
You'll find tips and support from kidney patients, delicious recipes, simple exercise plans and more.
Why not make a donation now?
(Every £ counts)