What have your Ph.D. studies focused on?

“As one of our vital organs, the lungs are crucial for our survival. It is of interest to us all to understand how they work and how we can develop new treatments for diseases that target the lungs. This is what my Ph.D. has focused on – the human lung. 

I have studied reasons why the lung develops diseases that are currently not curable and why there is damage occurring in the lung that does not seem to stop but progresses into the development of a disease that we die from. My focus has been on a specific lung disease called idiopathic pulmonary fibrosis (IPF). One of the easiest ways to describe this is thinking of the lung as a balloon that we can fill with air as we breathe. In IPF, the lung loses that ability as it becomes filled with other kinds of tissue that make it very stiff. Instead of an expandable balloon, the lung becomes more like a dense inflexible stone, making breathing more and more difficult.

In my research, I have been looking into how and why this occurs. In doing so, I have turned my attention toward the cells that form the barrier of the lung facing the outer environment. They are called epithelial cells. The main reason I have been looking into these cells is that they are the first to be damaged by the environment. Every day we breathe in particles from pollutants; when we are out in traffic, we breathe in the particles from car exhausts, and we become sick from viruses that attack this first layer of cells. So, they are interesting because they are the first line of defense against anything harmful that can be inhaled in our environment. In the diseased lung, like in the case of IPF patients, when we study how their lungs look, we see that those cells look very different compared to how they would normally appear in a healthy individual.

That tells us that they have a potentially active role in the development of disease, or they are harmed during disease development, or it could be both factors in actuality. So, it's of interest to understand what harms them exactly, why they seem to become harmed more as opposed to them trying to repair, and what are the reasons that they cannot become healthy again.

When I look at the studies included in the thesis, they are quite broad and cover several strategies to study the same disease but from different angles. I have used different kinds of models of pulmonary fibrosis to study various mechanisms. For those which we do not currently have the tools to study experimentally in the lab, we have built the models ourselves, such as for example stem cell-based lung models. For the more complex interactions, we still need animal models, and I've used them to identify potential novel contributors to the disease which we can potentially use to monitor the progress of disease in the future.

I have also been involved in more technical studies where we use techniques to isolate the cells from the lungs of animals to study them in a more isolated format, which we sometimes need to do when we have specific questions. Then we sometimes need something less complicated than a whole animal with a whole lung and I've also been involved in these studies where we have developed tools for visualization of the whole lung.

My main part of the project was in collaboration with industry, and this was to develop a novel experimental system of the lung in which we can model the changes in the epithelial cells in IPF. In this stem cell-based system, we have human lung epithelial cells in a 3D format in which they assemble to little “balls”, called organoids. These are structurally similar to the structures we use to breathe and we found that upon injury in our model, we can mimic the densening effects visibly similar to IPF when they become diseased. The cells in these organoids also change their identity in our model and become similar to the diseased epithelial cells we can find in the human IPF lung. This is very valuable because we have had limited tools to study the diseased cells unique in IPF. Now, we can do that experimentally. In the future, the hope is that the new model system developed in my PhD can be used to develop drugs that can treat these specific cells in the progression of disease and perhaps prevent the initiation of the disease altogether.

Today, IPF is a disease with only a two-to-three-year median survival rate following diagnosis. Many patients progress quickly, which is devastating for them because they don't have access to any cures or sometimes, not even enough symptomatic relief during the limited time they have left. So, we hope this model system will help us in pinpointing what the reasons are for the development of disease and what we can use from that to prevent the disease in patients before it develops,” explains Victoria.

How did you end up doing a Ph.D. at Lund Stem Cell Center?

“I have been doing my Ph.D. in Darcy Wagner's research group at Lund University, and in collaboration with AstraZeneca in Gothenburg. I’m originally from Lund, where I studied both my bachelor's and master's in biomedicine at Lund University and then did a short transition to the drug development industry, specifically AstraZeneca.

Following my master’s program, I participated in a training program where I got to see different parts of the drug development process and was placed in different departments at AstraZeneca in Gothenburg. This is how I got the interest in doing an industrial Ph.D. as opposed to only an academic one. I had experience in both academia and industry, so I wanted to join the best of both worlds into one Ph.D. project. I didn't want to have to choose.

Darcy Wagner, my academic supervisor, and I met at a lung conference where she was presenting. I saw her talk and at the time I had also just started to explore the lung. Afterwards, we got the opportunity to meet, and discuss, and I learned more about her research, which I thought was very exciting and was exactly the field that I wanted to go into. I brought her all my questions and thoughts around why the lung does not regenerate and we both realized that these questions could be the foundation for a Ph.D. project, that we could work on together.

I was very keen to do research both at AstraZeneca in Gothenburg and in the lab in Lund, get to know the different groups and collaborate with them on their terms and with their equipment. So, my thesis has really been a joint effort and we are all very excited from both the academic and industrial sides of my Ph.D. project,” highlights Victoria.

Can you tell us about the cover of your thesis?

“The cover, I drew myself. It's an artistic representation of the IPF lung. I first sketched the different structures of the lung. I started out drawing a healthy lung with all the very defined structures and airways. Then I came to think that well, during chronic lung diseases, we assume that the lung becomes damaged bit by bit and by things from the outside. So, I decided to do a watercolor of that sketch and then introduce some of the different colors that you can see in the image. Each color represents the different types of injuries that we come across, leading to the development of chronic lung diseases such as IPF.

You can see on the left side, which shows the lung lobes from the outside, that we have a relatively normal-appearing lung and we don't see any disease-related changes from the outside. This represents how when we see patients with lung diseases out in public, we cannot tell that they have a disease in their lungs just by looking at them. Their disease or illness is invisible in many ways, making it harder to sympathize with them on a day-to-day basis. We can’t see the challenges that they encounter during their everyday life, as opposed to when we see someone with a broken leg. We can look at them and feel and understand the struggles that they have.

This is the case for many of the patients with chronic lung disease. But when we look on the inside, we can very clearly see how the lung differs from what we would expect to see in a normal case. So, it's fully visible with all its diverse changes, and these appear quite messy. But to me, as a scientist, they also appear in one way, scientifically beautiful and intriguing, enticing me to explore them in more detail. What are they like? Why do they appear so?” describes Victoria.

What have you found the most enjoyable during your Ph.D. studies? 

”The most enjoyable aspect has been the way I've been allowed to do the research within my Ph.D. project, I was given freedom to explore many diverse aspects of the disease. The project is of course defined from the beginning, but then you can sort of tailor the angles or the types of studies depending on personal interest, and I got to do that here. Even if it was an industrial Ph.D., which many fear is a bit more rigid in one way because there are two collaborators, not just one, deciding what should be in the thesis. In my case, I have been given a lot of freedom to explore, and I found this fantastic and very, very stimulating. 

This also shows in the studies included in the thesis which are very diverse. We look at everything from complex animal models to specialized cell systems. So, I now have a broad spectrum of that experience, which I'm very grateful for. I think it has trained me to evaluate and design different kinds of studies, which is very valuable for me as a scientist in general,” notes Victoria.

What has been the most challenging aspect?

”Initially, the most challenging aspect was to organize it all together and to learn how to collaborate between two seemingly very different worlds -industry and academia. Two worlds that I initially thought had different ways of working, and different goals. One wants to develop novel drugs, the other wants to hunt for knowledge, for publications. 

In the beginning, I thought that was very different and we had to deal with more paperwork that maybe a regular Ph.D. student just based in academia wouldn’t have to deal with (e.g., research agreements, procedures around publishing, etc.). There were these additional steps from industry which comes from the patenting aspects. When science is published it becomes public and that can be a problem down the line if something sensitive is published beforehand, for example. So, these were processes I had to become familiar with and follow in my work.

Ultimately, this led to a more rewarding insight - both seemingly very different words strive towards the same goal. We want to have scientific knowledge that will create a better world for our patients and all the procedures that are in place, both in academia and in industry. These added procedures all have their reasons for being there in terms of what's good for the patients, how we can protect them if we use patient material, what needs to be regulated, etc.

After going through the challenges that I had initially faced, which at the time I felt were hard to navigate around, I felt that it's a good thing that these procedures are in place. They help to ensure that we're working ethically, that we are collaborating effectively, and that we also know what to expect from each other. With contracts in place, we can feel free to be open and honest with each other, from the beginning, on regulated terms. What I initially saw as challenging are useful tools that can enable a better research culture and more collaborative environment for us and also increase patient safety.

Then of course there was an added layer since I did my Ph.D. during the pandemic. That put quite a bit of strain on the ways we were working, but we managed well in the end. Also, since it was a respiratory disease that was circulating, for me in particular, why I was doing what I was doing became very evident. At the time we were all hesitant because we didn't know what was happening during the disease and what the long-term consequences might be – something that we are still finding out even now. So, it helped to put my research into perspective, and made me aware of how it could help the patients and general public down the line,” highlights Victoria.

What are your plans following your Ph.D. defense?

“I have secured a role in the drug development industry here at AstraZeneca. I will be using quite a bit of my experience from my Ph.D., which is exciting. In my new role, I will be designing novel experimental systems that will be used for the evaluation of safety risks within novel therapies in early drug development.

This is naturally a very exciting task and a very important task as well. While doing my Ph.D., I became aware how important it is to use the right types of experimental models which represent the key effects we want to mimic from disease. In the aspect of safety, if the experimental models are inappropriately designed, they may either underestimate the safety risks which carries over those risks to patients or overestimate the safety risks in a way which hampers continued development of a needed drug. Well-designed experimental systems help in highlighting the relevant safety risks which we can work on eliminating during the development of the drug. By seeing this early during this process, we can prevent the safety risks from showing in patients during clinical trials. So, it feels like a very difficult, but meaningful, task, and I'm happy and excited about what comes next,” expresses Victoria.

Would you recommend doing an industrial Ph.D. to others?

“Whether I would recommend doing an industrial Ph.D. all depends on the kind of experiences that one wants to get during the Ph.D. period. Some of us are very academically oriented, they want to explore all the bits of academia because that's where they envision themselves being. The question is much the same as asking whether one would recommend working at a particular company or institute, or with this particular profession. The answer all depends on where your heart is placed and what you want to explore.

For me, it was important to include both industry and academia in my Ph.D. I felt like having this additional industrial component to my project would help bring my research closer to the drug discovery process and to the patients. So, if you're keen, as I was, to have both worlds included then yes, I would absolutely recommend doing an industrial Ph.D. because it's very rewarding,” shares Victoria.

Any tips or advice for future Ph.D. students? 

“In terms of general tips and advice for future Ph.D. students, I think the most important bit is to try to have fun in all parts of the Ph.D. thesis. Have fun, even in those moments when we just want to sit down and cry and give up - there are a lot of those, especially when it comes to stress related to publications and projects not panning out the way we initially planned.

So, I really think it's important to, in those moments, sit back with a nice cup of coffee or tea, and take the time to think about what excites you most and what you enjoy doing. All the different research topics we work with, are really like a map presenting all possible directions, and you will always be at the point where you must choose. The choices you make should be guided by what you find most exciting. That will undoubtedly make it easier for you to follow through even when times are tough. Second, to make sure you make your Ph.D. unique and truly yours. In the end, when you defend, hopefully, you will be able to say; I made these choices because I was convinced that this would matter the most to patients, or that I believe this is the best way forward in advancing our knowledge around the topic,” concludes Victoria.