Research
My research interest is understanding how cells sense and adapt to reduced oxygen (hypoxia), a process fundamental to physiology and a major driver of human diseases. My research portfolio has focused on the interplay between chromatin regulation and gene transcription in hypoxia. Using functional genomics, cell biology, and molecular biology, my work has uncovered critical new mechanisms controlling the hypoxia response.
During my MRC-funded PhD at the University of Dundee, I identified the KDM2 family of histone demethylases as hypoxia-responsive HIF target genes in human cancer cells. ( Batie et al., Cells 2017) (10.3390/cells6010008). These enzymes are important epigenetic regulators, and also modify transcription factors, control RNA Pol II recruitment, and are often dysregulated in cancer. My findings generated key evidence for crosstalk between KDM2A/B and hypoxia.
As a PDRA at the University of Liverpool, I discovered that hypoxia rapidly reprograms chromatin through oxygen-sensitive changes to histone methylation (Batie et al., Science 2019) (10.1126/science.aau5870). This work defined a molecular mechanism whereby KDM5A functions as a direct oxygen sensor, and inhibition of KDM5A triggers H3K4me3 hypermethylation and coordinates activation of the hypoxia transcriptional response. This seminal work was published back-to-back with the group of Nobel Laureate William Kaelin (10.1126/science.aaw1026), whose work elucidated oxygen-sensing by the histone demethylase KDM6A controls H327me3 levels and transcriptional repression in hypoxia, alongside a commentary in the same publication (10.1126/science.aaw8373). These findings have profound implications for our understanding of physiological and pathophysiological phenotypes and cell fates in environments subject to oxygen fluctuations, such as the tumour microenvironment, through direct effects on chromatin, and will be important in further elucidating mechanisms by which chromatin modifier dysregulation drives disease.
Building on my previous studies, using genomic and transcriptomic approaches, I have characterised chromatin accessibility changes in response to changes in oxygen availability (Batie et al., Biochemical Journal 2022) (10.1042/bcj20220008). This has shed light on the basic molecular mechanisms underpinning gene expression regulation in hypoxia, and revealed that chromatin accessibility is dynamically controlled by oxygen levels.
I have also investigated molecular crosstalk between hypoxia and inflammation, and, in collaboration with Dilem Shakir, defined the contribution of NF-kappaB to hypoxia-inducible changes in gene expression (Shakir et al., EMBO reports 2025) (10.1038/s44319-025-00651-x).