Sven Turkalj

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.

I am also studying the molecular and cellular bases of AML relapse in a subset of patients harbouring the IDH1 gene mutation. A recent clinical trial enrolling IDH1 mutant patients tested the novel Ivosidenib + Venetoclax +/- Azacytidine treatment, achieving encouraging remission and survival rates. Nevertheless, several patients still relapsed. It is a common view that, in AML patients who ultimately relapse, therapy fails to eradicate resistant leukaemia stem cells, which eventually re-seed the disease. Furthermore, genetic and/or epigenetic clonal evolution selects for resistant clones in the context of treatment-imposed evolutionary pressures. By applying novel tools combining high-sensitivity genotyping of single cells to their molecular landscapes, and by using primary AML samples from this trial, I hope to uncover mechanisms of therapy resistance, which may inform on future clinical strategies. 

GTAC enables parallel genotyping of multiple genomic loci with chromatin accessibility profiling in single cells

Journal article

Turkalj S, Jakobsen NA, Groom A, et al. 2023, Cell Stem Cell

https://doi.org/10.1016/j.stem.2023.04.012

A Phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies

Journal article

Lachowiez CA, Loghavi S, Zeng Z, Tanaka T, Kim YJ, Uryu H, Turkalj S, et al. 2023, Blood Cancer Discovery

https://doi.org/10.1158/2643-3230.BCD-22-0205

Genotyping of multiple genomic loci with chromatin accessibility profiling in single cells links clonal hierarchy with epigenetic variation in Acute Myeloid Leukemia

Conference paper

Turkalj S, Jakobsen NA, Groom A, et al. 2022, Blood (Supplement 1)

10.1182/blood-2022-163139

Single-cell analysis of human clonal hematopoiesis identifies distinct impact of DNMT3A and TET2 mutations on hematopoietic differentiation

Conference paper

Jakobsen NA, Turkalj S, Stoilova B, et al. 2022, Blood (Supplement 1)

10.1182/blood-2022-166474

Mechanisms of B Cell Receptor Activation and Responses to B Cell Receptor Inhibitors in B Cell Malignancies

Journal article

Efremov D, Turkalj S, and Laurenti L., 2020, Cancers

https://doi.org/10.3390/cancers12061396

Inhibition of SYK or BTK augments venetoclax sensitivity in SHP1-negative/BCL-2-positive diffuse large B-cell lymphoma

Journal article

Sasi BK, Martines C, Xerxa E, Porro F, Kalkan H, Fazio R, Turkalj S, et al., 2019, Leukemia 

10.1038/s41375-019-0442-8

SHP1 Deficiency Is Responsible for the Constitutive Activation of the BCR Pathway in GCB DLBCL

Conference paper

Sasi BK, Turkalj S, Kalkan H, et al., 2018, Blood (ASH)

10.1182/blood-2018-99-118120