What have your Ph.D. studies focused on?
“Human hematopoietic stem cells (HSCs), also known as blood stem cells, are incredibly important as they serve as the basis for current stem cell transplantation therapies and can repopulate the whole human blood system. So, in my research with the Stem Cell Regulators research group, we've been interested in better understanding HSCs and how they are regulated to find ways to expand or cultivate these stem cells for future therapies. At the end of the day, our goal is to improve their availability for patients with leukemia and other blood disorders. Today there is a notable lack of bone marrow donors and, while cord blood could be a potential source for today’s cell therapies, there is not enough stem cells per one unit of cord blood. This means that while cord blood is successful for the treatment of children with such disorder, when it comes to treating adult patients, there is just not enough stem cells present.
Therefore, my studies have focused on screening many different genes for their capacity to expand HSCs. The main challenge though is that once you place these cells into the culture, they start differentiating, meaning that they lose their stem cell potential and no longer have the same therapeutic potential. So, we have been looking into ways to preserve this potential and to expand them.
We also explored small molecules as potential drugs that have the capacity to expand HSCs in culture. Several years ago, a compound called UM171 was discovered by another research group and was a sort of revolution in this field because it started expanding cord blood cells in a way that no one had ever seen before but no one knew how it worked. In our group we had an interest to find the mechanism of action to explain what was happening. This is one of the major studies in my PhD thesis, where we uncover the molecular mechanism behind the UM171 induced cell expansion.
Here we discovered that this molecule is a rare class of drugs that redirects the proteasomal degradation in the cell towards certain proteins and triggers targeted degradation. It turned out that UM171 triggered degradation of a transcriptional repressor complex which allows the cells to preserve the phenotype of stem cells and to propagate. UM171 molecule recently cleared phase II clinical trials for improving cord blood transplantation therapies and our study revealed the basis of UM171 mechanism of action,” explained Kristijonas.
Can you tell us more about the cover of your thesis and the inspiration behind it?
“The inspiration for the cover of my thesis is mainly my hobbies - which I have quite a few of. Ever since I was a kid, I have loved to explore nature – from stargazing to fishing to sailing and camping, or simply just being in the forest. So, I used an AI art generator known as Dall e, which can generate images by descriptions given. I incorporated the DNA strand into my list of hobbies, and the generator did the rest. Then in the end, my wife had some final adjustments, for example, adjusting colors and adding the mirror effect,” noted Kristijonas.
How did you end up doing a Ph.D. at Lund Stem Cell Center?
“I’ve always been interested in science topics like biology and chemistry, this probably has something to do with my love for nature and exploration. So as a bachelor’s student at Vilnius University in Lithuania, I studied biochemistry. At the time, I thought I really enjoyed chemistry but the more I studied molecular biology it became much more interesting to me. So I began to shift towards biology and completed my master’s degree in molecular biology also at Vilnius University before making my way to Lund Stem Cell Center.
As a master’s student I already knew that I wanted to do a Ph.D. within the stem cell topic. I was looking for opportunities to a Ph.D. in the field and Lund University was on my radar, so I contacted a few principal investigators here working within topics I was interested in. That’s how I first met my supervisor Professor Jonas Larsson. He put me in contact with the director of the Center’s Research School for Stem Cell Biology at the time who suggested that I enroll in the preparatory program. I joined the Larsson lab first through this program via an Erasmus internship before staying on to do a Ph.D.,” recalled Kristijonas.
What have you found the most enjoyable during your Ph.D. studies?
“First, the department as a whole and all the people around. Another aspect is the freedom to ask scientific questions and design experiments to answer those questions. Then there are all of the facilities that are available within the Center, for example the FACS facility, which provides the needed support and help to do your experiments.
Though of course part my Ph.D. studies were interrupted by COVID-19, but I still had a chance to go to a few conferences before that. Meeting people at the conferences and presenting your work is also a big part of Ph.D. process,” realized Kristijonas.
What has been the most challenging aspect?
“While COVID-19 was a challenge, it wasn’t the biggest challenge of all. Personally, I haven’t faced any specific challenge, but experienced the general aspects that every Ph.D. student faces and must overcome. Mainly that we experience so many failures along the way that is can be difficult sometimes to look at the positive things that are happening. There can be many failures that can bring you down and it's difficult sometimes to motivate yourself afterwards. But that's what you learn as a Ph.D. student to accept these ups and downs and come to terms with the fact that before you succeed at something you will fail along the way. It's quite a good lesson to learn, it prepares you for the next step, whether that is a postdoc or something else,” clarified Kristijonas.
What are your plans following your Ph.D. defense?
“Currently, we have several exciting projects running at the lab, that I would like to be a part of. I will likely stay in the area and for now, finishing these projects and exploring some options where I would like to establish myself next. Now, with all the experience gathered during my Ph.D. studies, it could be quite tempting to do a postdoc,” contemplated Kristijonas
Any tips or advice for future Ph.D. students?
“It is important to set priorities and plan your time accordingly. Focus on the most important experiment, like the experiments that would have the most impact in your thesis. It is too easy to get distracted or sidetracked with small, exciting experiments which often won’t help you much in accomplishing the main goal. So, stay focused on the impactful experiments.
Also, take your time to explore the courses that are available during the Ph.D. to develop the skills and knowledge that you will need afterwards. There are so many different courses that can be helpful whether you want to continue in academia or move into the industry.
The last tip is to remember that the Ph.D. is very much like a marathon, not a sprint. So, my advice here is to remember to take care of your well-being. It can be difficult in the beginning of the Ph.D., especially, but it is important to remember to make time for yourself and to do the things that you enjoy,” concluded Kristijonas.