BM, MA, DPhil, FRCP(UK)
Professor of Renal Medicine
- Group Head / PI
- Consultant Physician
- Assistant Director of Graduate Studies
- Deputy Director of Graduate Entry Medicine
Research interest: transcriptional responses to hypoxia in cancer biology
My group works on the mechanisms by which cells sense and respond to reduced oxygen (hypoxia) and their role in the development of cancer. These pathways are activated both by the tumour microenvironment and by oncogenic mutation, regulate many of Hanahan and Weinberg’s hallmarks of cancer, and promote tumour growth and resistance to treatment. Working alongside Nobel Prize winner Sir Peter Ratcliffe, I helped elucidate the oxygen sensing and signalling pathways that link the transcriptional regulator, hypoxia inducible factor (HIF) to the availability of oxygen. Importantly, these involve the VHL tumour suppressor, which is mutated in clear cell kidney cancer, and which in turn provides a paradigm for studying the role of hypoxia pathways in cancer.
We are currently focussed on using high throughput sequencing and bioinformatic approaches to study the transcriptional and epigenetic responses to hypoxia in cancer, using kidney cancer as a model tumour type. Specifically, technologies such as RNA-seq, ChIP-seq, ATAC-seq, and capture-C (to study chromatin looping) have allowed us to characterise widespread transcriptional and epigenetic responses to hypoxia and VHL loss across the genome. These responses include changes that help drive cancer progression, as well as many that have neutral effects, but are simply co-acquired during activation of the pathways. Combining these analyses with WGS, WES, GWAS and single cell RNA-seq, has allowed us to distinguish key components that are driving the cancer and to separate them from bystander events. These, in turn, provide attractive novel therapeutic strategies, either as new candidate targets or by indicating new combinations of existing therapies.
Pan-Cancer Analysis of Tissue and Single-Cell HIF-Pathway Activation Using a Conserved Gene Signature
Lombardi O. et al, (2023), SSRN Electronic Journal
Pan-cancer analysis of tissue and single-cell HIF-pathway activation using a conserved gene signature.
Lombardi O. et al, (2022), Cell reports, 41
Re-activation of HIF signalling pathway in the epicardium improves heart regeneration after myocardial infarction
Gamen E. et al, (2022), CARDIOVASCULAR RESEARCH, 118
Epicardial re-activation of HIF signalling pathway improves heart regeneration in a neonatal mouse model of myocardial infarction
Gamen EE. et al, (2022), EUROPEAN JOURNAL OF HEART FAILURE, 24, 10 - 10
Altered regulation of DPF3, a member of the SWI/SNF complexes, underlies the 14q24 renal cancer susceptibility locus.
Colli LM. et al, (2021), American journal of human genetics, 108, 1590 - 1610