Gillian Caalim

Activation of the transcription factor HIF-1 by HMGN1 in Acute Myeloid Leukaemia

About me

I completed my MSci Biomedical Science degree from the University of Sussex in 2022. My third year project involved the investigation of a novel protein-protein interaction and its effect on Wnt signalling in acute myeloid leukaemia, whilst my fourth year project explored the mechanisms to target transcription factors to subvert multiple myeloma. My interest in blood cancers has led me to pursue a PhD at the University of York, where I joined Dr Katherine Bridge’s lab to study the role of hypoxia inducible factors (HIFs) in haematological malignancies.


My project

The chromatin modulator HMGN1 has been shown to decompact chromatin to allow expression of transcription factors such as hypoxia-inducible factors (HIFs). HMGN1 is also located on chromosome 21 which is one of the most commonly amplified regions in acute myeloid leukaemia (AML). There is growing evidence to show that alterations in the compaction of chromatin caused by HMGN1 may promote AML, though there is no current mechanistic explanation as to how HMGN1 exerts this role. Preliminary data show that HMGN1 is a novel HIF regulator, and we propose that HIF-1a is involved in the ability of HMGN1 to promote AML. My project therefore aims to determine the mechanism by which HMGN1 regulates HIF-1a transcription activity and to identify the contribution of HIF1-a in the pathogenesis of HMGN1-driven AML.