dr. Kaat Durinck (PhD)
During my PhD, I performed a functional dissection of the transcriptional networks that govern normal T-cell development and T-cell acute lymphoblastic leukemia (T-ALL) development. T-ALL is a highly aggressive blood disorder arising from malignant transformation of thymocytes. While originally associated with poor prognosis, intensified T-ALL therapy has led to remarkable improvements in survival of these patients. Unfortunately, these therapeutic schemes are associated with severe acute and long-term toxicities, thus demanding for further research in order to design more precision medicine oriented treatment. To shift towards this personalized medicine approach, a more profound understanding of the molecular basis of T-ALL progression is required. Several decades of genetic studies in T-ALL have uncovered a remarkable heterogenous and complex landscape of combined oncogenic and loss-of-function mutations that contribute to malignant thymocyte transformation. One of the major challenges in T-ALL research is to unravel in detail how the diverse complement of oncogenes and tumor suppressors functionally contribute to T-ALL pathogenesis and response to therapy and this was my main focus during my PhD track. During my post-doctoral fellowship I will expand the technical repertoire for the study of epigenetic alterations, DNA architecture, perturbed enhancer landscapes and gene regulatory networks implicated in amongst others regulation of DNA repair in cancer cells. This work will be oriented towards discovering novel therapeutic vulnerabilities as prelude to novel therapies.
In 2010, I obtained a Masters degree in Biochemistry and Biotechnology at Ghent University (Belgium). Thereafter, I became a full-time doctoral fellow in the lab of Prof. Frank Speleman (IWT fellowship 2010-2014) entitled: 'Unravelin the role of PHF6 in normal T-cell development and T-cell acute lymphoblastic leukemia'. In 2015, I received a grant from the 'Flemish League against Cancer' (VLK) to finalize my PhD track. Next, in April 2016 I obtained the PhD degree 'Doctor in Medical Sciences' at Ghent University. Thereafter, I received a post-doctoral fellowship grant from Ghent University (BOF) for a 3-year mandate.
- 'Novel TAL1 targets beyond protein-coding genes: identification of TAL1-regulated microRNAs in T-cell acute lymphoblastic leukemia'. Leukemia, 2013. (PMID: 23448994)
- 'The H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia'. Blood, 2015 (PMID: 25320243)
- 'ZEB2 drives immature T-cell lymphoblastic leukemia development via enhanced tumour-initiating potential and IL-7 receptor signaling'. Nature Communications, 2015. (PMID: 25565005)
- 'GATA3 induces human T-cell commitment by restraining Notch activity and repressing NK-cell fate'. Nature Communications, 2016. (PMID: 27048872)
- 'The Notch driven long non-coding RNA repertoire in T-cell acute lymphoblastic leukemia'. Haematologica, 2015. (PMID: 25344525)
- 'Long noncoding RNA signatures define oncogenic subtypes in T-cell acute lymphoblastic leukemia'. Leukemia, 2016. (PMID: 27168467)
- 'Novel biological insights in T-cell acute lymphoblastic leukemia'. Experimental Hematology, 2015. (PMID:26123366)
- 'Characterization of the genome-wide TLX1 binding profile in T-cell acute lymphoblastic leukemia'. Leukemia, 2015. (PMID: 26108691)