My research focuses on understanding the molecular and cell biology of the hypoxic microenvironment. Hypoxia (low oxygen) is key in many pathological settings including wound healing, inflammation, ischemia and cancer. Regions of hypoxia in tumours are associated with worse survival, chemotherapy and radiotherapy resistance. Tumour hypoxia arises from the combination of high metabolic and proliferative rates and aberrant vascularisation. The hypoxic tumour microenvironment is also acidic as metabolic acid accumulates in poorly-vascularised areas. Hypoxia induces a transcriptome shift under the regulation of the transcription factors HIF1α and HIF2α, which are stabilised in hypoxia. HIFs regulate genes in key "hallmarks of cancer" processes that enable adaptation to the hypoxic tumour microenvironment. In many cases anti-angiogenic therapy, such as bevacizumab, increases tumour hypoxia and hypoxic adaptation is a major mechanism of resistance to anti-angiogenic therapies. Understanding the molecular consequences of hypoxia and how to target hypoxic regions of tumours is key in improving tumour patient survival.
My research interests are:
Tumour Microenvironment Stress
Molecular Adaptive Responses
Invasion and metastasis
Functional shRNA/siRNA screens - Induced essentiality
Cancer stem cells
Our work is generously funded by: The Medical Research Council, Breast Cancer Now and Bowel & Cancer Research.
I have a self-funded PhD studentship available for October 2020 start please contact me directly to find out more details.
HAIDER S, MCINTYRE A, VAN STIPHOUT RG, WINCHESTER LM, WIGFIELD S, HARRIS AL and BUFFA FM, 2016. Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia. Genome biology. 17(1), 140 DA MOTTA, L. L., LEDAKI, I., PURSHOUSE, K., HAIDER, S., DE BASTIANI, M. A., BABAN, D., MOROTTI, M., STEERS, G., WIGFIELD, S., BRIDGES, E., LI, J. L., KNAPP, S., EBNER, D., KLAMT, F., HARRIS, A. L. and MCINTYRE, A., 2016. The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer: Oncogene Oncogene. MCINTYRE, ALAN, HULIKOVA, ALZBETA, LEDAKI, IOANNA, SNELL, CAMERON, SINGLETON, DEAN, STEERS, GRAHAM, SEDEN, PETER, JONES, DYLAN, BRIDGES, ESTHER, WIGFIELD, SIMON, LI, JI-LIANG, RUSSELL, ANGELA, SWIETACH, PAWEL and HARRIS, ADRIAN L., 2016. Disrupting hypoxia-induced bicarbonate transport acidifies tumor cells and suppresses tumor growth: Cancer Research
HANI CHOUDHRY, ADRIAN L. HARRIS and ALAN MCINTYRE, 2016. The tumour hypoxia induced non-coding transcriptome Molecular Aspects of Medicine. 47-48, 35-53