What have you been working with during your PhD?
Whilst researching in the Proteomic Hematology group I have been trying to understand blood production throughout life, to shed light on why children and adults develop different subtypes of leukemia.
I started my PhD focused on identifying differences in the proteome - the protein content of the cell - in fetal and adult blood stem and progenitor cells. We used a mass spectrometry–based quantitative proteomics approach to quantify close to 7000 proteins per cell, giving us a very nice overview of the proteome of the earliest developing cells of the blood system. We were able to identify several key differences in the proteins expressed in progenitors during early life and adulthood, including those involved in processes such as defence against reactive oxygen species and inflammation.
I then worked on a project - led by postdoc Kristyna Pimkova – in which we optimised a very nice method of exploring the redox state of a very low number of cells. We used this method to identify reversible cysteine oxidations and found that fetal blood stem and progenitor cells have higher levels of oxidation than in the adult, and that this oxidation level increases even further upon leukemic transformation.
In my next project, I investigated what drives lineage choices in stem and progenitor cells and the differences between these during fetal and adult life. This is important to understand, as lineage-biased hematopoietic progenitor cells have been shown to be highly susceptible to leukemic transformation. In this study, we also further developed our mass spectrometry workflow, allowing us to decrease the number of cells needed to run our proteomic experiments by five-fold. This advancement allowed us to take a closer look at the molecular mechanisms regulating rare blood progenitor cells in greater detail than ever before.
Finally, moving into a leukemic setting, we have investigated functional and molecular differences between fetal- and adult-derived leukemia using a mouse model with inducible expression of the MLL-ENL fusion oncogene, generated by the Bryder lab. We have been dissecting the intrinsic capacities of the cells, as well as the role of the extracellular environment, in driving acute leukemia. With this approach, we hope to identify ontogeny-specific leukemia vulnerabilities, or even ways to enhance leukemia resistance in infants and adults, by exploiting the findings from looking at leukemic protein signatures.
How did you end up doing a PhD in Lund?
I was born in Russia and moved to Sweden when I was five years old. I grew up on the west coast, north of Gothenburg, and moved to Lund for my undergraduate degree in engineering in biotechnology. I heard about the preparatory program at Lund Stem Cell Center from some friends, applied and was accepted. I was interviewed by Jenny Hansson, head of the Proteomic Hematology group, for a position in her lab and we really clicked. I started my Master’s thesis in her group and continued to a PhD, which I officially started in October of 2016.
What have been the most challenging aspects of your PhD?
Getting enough papers to defend my thesis has been a challenge. Meeting the requirements, especially researching in a very competitive field, can be tough.
What have been the best aspects?
Being surrounded by so many excellent researchers has been great! There are so many experts in their respective fields to give you advice and input on your projects. There’s also the sense of community among the PhD students.
What will you do after you defend your thesis?
I have actually already joined the lab of David Kent at the University of York in the UK. I’m working with optimizing a method of expanding hematopoietic stem cells ex vivo. I’ve managed to make it back to Lund for my PhD defence, but I’ll be headed back to the UK soon after I have defended.