Clare Jonas
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A day in the life: Pedro Santos e Sousa, graft versus host disease researcher

Clare Jonas
Posted by
17 Sep 2018

Dr Pedro Santos e Sousa is a Bloodwise-funded Research Associate at University College London, where he works on graft-versus-host disease, a potentially life-threatening condition which can affect people who have had a stem cell transplant. Below, he tells us about training as a medical doctor and as a blood cancer researcher, his work in Professor Ronjon Chakraverty’s lab In the Institute of Immunity and Transplantation at University College London, and going hiking with his family.

Dr Pedro Santos e Sousa at work in the lab
Dr Pedro Santos e Sousa at work in the lab

You’re both a medical doctor and a blood cancer researcher. How did that happen?

I trained as a doctor first. My interest in haematology – which is the study of blood – began in my fourth year of medical school in Portugal, when I first had contact with this fascinating specialty. What I found most appealing about it was how much it had progressed in the last few decades and how quickly the knowledge acquired from lab-based research was being translated into clinical practice. When I finished my haematology training in 2012, having participated in small research projects along the way, it became clear to me that I wanted to become a physician-scientist so I could treat people as well as contribute to advancing our knowledge of blood disorders and their treatment. At that point, I had developed a particular interest in stem cell transplants and immune cell therapy, so when I had the opportunity to join Prof. Ronjon Chakraverty’s Transplantation Immunology Group as a PhD student, it was a perfect fit. After my PhD, I stayed at Ronjon’s lab and am now working on a new project.

 

What are you working on?

Stem cell transplants can potentially cure blood cancers, but they carry some big risks, including graft-versus-host disease (GvHD), the main focus of my research. GvHD is a serious and potentially life-threatening complication of ‘allogeneic’ stem cell transplants, where the stem cells come from a donor and are given to a recipient. Up to seven in ten people undergoing this type of transplant can develop GvHD. In particular, I am interested in identifying differences in the gene activity of donor white blood cells that react against the recipient’s cells in GvHD. I am also looking at white blood cells isolated from different organs and tissues in GvHD, and want to see how these cells interact with their environment and each other, in the hope of identifying processes specific to each organ or tissue that may be targeted with drugs.

 

Why do we need the research you do?

In GvHD, the donor stem cells attack the healthy cells of the recipient, resulting in damage to some parts of the body, like the skin, liver and intestines. Although we know a lot about GvHD, it is still not clear why it only involves some organs, nor why they are not all affected to the same extent.

Furthermore, while we can treat GvHD, not everyone responds to treatment, and responses to treatment in individual organs can vary even in individual patients. Current treatment options are very limited, largely based on suppressing the activity of the transplanted white blood cells, which unfortunately, makes them less capable of fighting the cancer cells and infections.

In Ronjon’s lab, we are tackling these problems by studying how white blood cells created by transplanted stem cells respond to host cells in different organs. Previously, we have identified an interaction between donor white blood cells and host Langerhans cells (found in the skin) which is crucial to the development of GvHD in the skin. We also found a molecular interaction that can make white blood cells in the transplant more toxic to host skin cells. Both these discoveries are really exciting for us because they could be very helpful for people with blood cancer.

 

A special type of staining called ‘immunofluorescence’, which labels different cells carried out by Dr Cara Lomas, another researcher in Ronjon’s lab. It shows donor white blood cells (dyed green cells next to arrows) in the skin of a patient with GvHD.

A special type of staining called ‘immunofluorescence’, which labels different cells carried out by Dr Cara Lomas, another researcher in Ronjon’s lab. It shows donor white blood cells (dyed green cells next to arrows) in the skin of a patient with GvHD.

 

What does your work mean for people who have blood cancer?

For several blood cancers, stem cell transplantation is the only treatment that might cure these diseases. Although the scientific advances in the last 2 decades have made stem cell transplants safer and available to more people, the success of these treatments is still largely limited by GvHD. Our work could help develop precision therapies directed at blocking GvHD in individual organs, which would allow us to move away from the non-specific treatments we have now.

 

What do you do at work on a day-to-day basis?

My work is divided between lab work, data analysis, and teaching.

The lab work is varied but one of the main techniques I use is flow cytometry, which allows me to characterise and sort different types of cells for later testing. The results from these tests are compiled in data sets containing the genetic information which I then analyse to pick out what is important for the questions we want to answer.

Some of my teaching is with medical students in year 4, who are learning about clinical practice, but I also supervise students who are doing Master’s degrees so that they can learn about different research techniques in the lab.

 

Pedro counting white blood cells under the microscope.

 

You are in the early stages of this project. What are you looking forward to exploring later on?

In this project we are looking at individual white blood cells in great detail, so we can see what genes are active in them in different places and times. This means we will be able to understand how these white blood cells react to cells from different organs over time.

Our current findings suggest that early on in GvHD, a group of donor white blood cells develops that is resistant to glucocorticoids, a type of steroid drug that is used to treat GvHD. These treatment-resistant cells are likely to grow in tissues in the body that come into contact with things from the outside world regularly, like the skin, the lungs and the gut.

The results from our experiments will allow us to gain a deep understanding of what these cells are like, which could potentially identify which people’s GvHD could develop resistance to glucocorticoids.

 

What common misconceptions do people have about your job?

A lot of my time is spent working on research that can be used in clinical settings. People often think that the transfer of information from the lab to the clinic is easy, but there are lots of steps required to bring these advances to daily practice.

 

What's your favourite thing about your work?

For me, the most exciting thing about my work is that I’m continuously learning, either through my own experiments and analysis, or by talking to my colleagues and collaborators. As researchers, our work is never finished and we can always go further; the answers to our initial research question generate new questions and open new avenues to explore.

 

What's one of the hardest things about your work?

Perhaps the hardest thing is all the administrative work that is required to keep the lab working and the project flowing smoothly; this can take up a considerable amount of time. I spend quite a lot of time ordering items for use in the lab, liaising with other research groups to book equipment, and doing risk assessments.

 

What do you do when you’re not in the lab?

For me the best way to unwind is to spend quality time with my family. We’ve recently discovered the joys of hiking. Around London, we like to go to places like the Chess Valley and Epping Forest, but we’ve also explored further afield when we’re on holiday.

 

Pedro on a hiking visit to the New Forest

 

Is there anything you’d like to say to Bloodwise supporters?

I would like to express my sincere gratitude to all Bloodwise supporters for helping to make sure our research on GvHD can be done. Our Bloodwise-funded work has given us new insights into how donor white blood cells work in GvHD. This has provided us with the foundation for developing precision therapies for GvHD that can work on the disease without compromising the transplant’s beneficial effects of killing cancer cells.

 

You can follow the work Pedro and the other researchers at the Institute of Immunity and Transplantation on Twitter @iit_ucl, and you can read about Pedro’s latest research in JCI Insight and Frontiers in Immunology.

 

All the amazing research we fund can only happen thanks to support from you. Find out more about how you can help us continue our live-saving research, or about the GvHD research we fund.

 

If you would like more information and support on blood cancer, you can read our Online Patient Information, or speak to one of the Support Line Team on Freephone 0808 2080 888 (Monday-Friday 10am-4pm). You can also email support@bloodwise.org.uk.

 

We’ll be back soon with another day in the life.