Inside the lab with Professor Simon Satchell
We caught up with Professor Simon Satchell, from the University of Bristol, about his new Kidney Research UK-funded work in diabetic kidney disease (DKD) and got a sneak preview of his lab being set up. Simon starts work on his latest project this month; he and his team will be looking at new treatments for the kidney damage that can happen in patients who have diabetes.
Thanks for talking to us about your research Simon. Please could you tell us about your work with Kidney Research UK in diabetic kidney disease?
Our lab is studying the endothelial glycocalyx in diabetic kidney disease. This is a layer which lines the inside of all blood vessels throughout the body. In the tiny blood vessels that make up the kidney filters (known as glomeruli), the endothelial glycocalyx performs a key role in filtering the blood.
Damage to the glycocalyx occurs in conditions including diabetic kidney disease, making the filters leaky. This means that larger molecules, such as protein, are lost in the urine in a process called proteinuria. Patients with diabetic kidney disease see gradual kidney damage and often eventually kidney failure.
Please could you tell us about your previous work and how you are planning to build upon it?
We have received several grants from Kidney Research UK and this funding has allowed us to progress our research, and build knowledge and experience in our team. Our first breakthrough in this area was enabled by the Kidney Research UK/John Feehally-Stoneygate project grant we received in 2015. We identified that molecules found within kidney cells called matrix metalloproteinases (MMPs) were responsible for damage to the glomerular endothelial glycocalyx in models of diabetes. Importantly, we also found that we could use chemicals to prevent this damage, protecting the health of the glomerular filters and preventing proteinuria. This work showed that developing drugs which could target these MMPs might benefit kidney disease patients.
What will your new project involve?
We have been building on this discovery to find a way to treat people with diabetic kidney disease and are currently exploring two strategies. The first is to see if we can repurpose an existing medicine, and the second is to identify a specific individual MMP which we can target to enable the development of precision medicine.
Doxycycline is a medicine which is already licensed for use in humans, meaning it has a potentially quicker path to patients than a brand-new treatment, as all the rigorous safety testing is complete. Doxycycline at low doses is known to block MMPs. Our Kidney Research UK project grant enabled us to test doxycycline in a model of type 1 diabetes and our results show that it can successfully protect the glycocalyx and reduce proteinuria. These exciting results are being prepared for publication. The next step with this work is to move on to a model of type 2 diabetes, as this more relevant to the majority of human disease. We have applied for funding for this work.
This all sounds really promising. Do any challenges remain?
Some MMP inhibitors have been tested in patients for other conditions, they have caused side effects. This seems to be because they interfere with other MMPs which are performing beneficial functions. To overcome this problem, in our new Kidney Research UK grant starting shortly, we aim to identify one single MMP which can be blocked specifically in the kidney filters. This should enable glycocalyx protection without significant side effects.
Because endothelial glycocalyx damage is involved in diseases affecting multiple organs, there is huge potential to improve health and well-being. For example, people with diabetic kidney disease often have diabetic eye disease and heart disease. We are also actively researching in these areas show that glycocalyx protection offer hope for these people.
In the lab with Dr Monica Gamez
Dr Monica Gamez is the senior research associate working on the new Kidney Research UK grant. She shared an insight into her daily work in Simon’s lab.
On a typical day, I usually get into the lab and first start by getting a bit of admin done on my computer while I have a cup of coffee. This includes answering emails, ordering materials needed for upcoming experiments, and mapping out an experiment for that day.
It is then time to head into the lab! A lot of the work we do in the lab involves the use of cells, which are very prone to contamination with bacteria or mould. To protect myself and the cells, cell work is done under a special lab hood to keep the local environment as clean as possible.
Many of our experiments involve treatments of cells with something that we know will make them ‘sick’, to mimic a diabetic environment, and then treating them with a potential therapeutic compound. We can then observe them down the microscope, using special imaging techniques to see how the cells respond to our treatments.
Whilst lab work is essential to the work we do; we get a lot of the exciting data days later after analysis has been done. This means that a large amount of time is spent running analysis on results which were obtained in the lab in previous days.
After a full day of work in the lab and exciting analysis, it is time to pack up and go home. Although working days in the life of a scientist may all look similar, in reality they are always changing. Every new experiment yields new results, involves new techniques, and leads to new answers to really important questions. This is one of the many reasons why science is so exciting!
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