Sven Turkalj

B.S. Biological Sciences and Biotechnology; M.S. Functional Genomics; M.S. Genetics

DPhil Student

Clarendon Fund Scholar
RDM Scholar on the WIMM Prize Studentship

I am a DPhil student working in the Vyas group. I obtained my Bachelor's Degree in Italy, at the University of Trieste, where I studied the inhibitors of apoptotic and B-cell receptor pathways in the context of B-cell malignancies, supervised by Prof. Dimitar Efremov. I obtained my Master's Degree in Functional Genomics at Trieste and then in Genetics from the University of Paris. In France, I worked on a novel mutant of the transcription factor PU.1, under the supervision of Dr. Olivier Bernard at the Institute Gustave Roussy.

My current work is focused on the molecular mechanisms leading to clonal expansion of haematopoietic stem cells and early progenitors, in the context of clonal haematopoiesis, a state associated with higher risk of developing Acute Myeloid Leukemia (AML) and cardiovascular disease. In particular, I am interested in how somatic mutations in epigenetic regulators, such as TET2, DNMT3A and ASXL1, confer clonal advantage during haematopoietic differentiation, and which pathways are corrupted in the process. Defining the direct and indirect targets of these proteins, the changes in chromatin accessibility caused by these mutations and the impact of those on self-renewal and lineage specification, remains a largely unresolved question in the field. Importantly, understanding these mechanisms would contribute in elucidating the earliest steps of leukemia stem cell formation, the fuel of haematopoietic transformation.

Another question I am interested in revolves around AML more directly: it is not completely clear why, following chemotherapy, some patients achieve definitive cure while others relapse. It is a common view that, in the patients who ultimately relapse, therapy fails to eradicate chemo-resistant leukaemia stem cells, which eventually re-seed the disease. An additional (not mutually exclusive) hypothesis is that the immune microenvironment in relapsing patients is modified to such extent to be permissive for disease relapse. By using primary human AML samples of chemotherapy-treated patients, I hope to uncover the differences in the immune cells between cured and relapsed patients and elucidate the mechanisms leading to relapse-associated immune disfunction.