Alan McIntyre

Contact

• workC209a, Biodiscovery Institute, Science Road, University of Nottingham, NG7 2RD
  University Park
  Nottingham
  NG7 2RD
  UK
• work0115 823 1547
• Alan.Mcintyre@nottingham.ac.uk

Expertise Summary

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

Epigenetics

Transcription

Metabolism

Acidosis

Translation

Angiogenesis

miRNAs

Invasion and metastasis

Functional shRNA/siRNA screens - Induced essentiality

Biomarkers

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.

Selected Publications

• 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

• View all publications

• HANI CHOUDHRY, ADRIAN L. HARRIS and ALAN MCINTYRE, 2016. The tumour hypoxia induced non-coding transcriptome Molecular Aspects of Medicine. 47-48, 35-53
• 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
• 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 A and HARRIS AL, 2016. The Role of pH Regulation in Cancer Progression. Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer. 207, 93-134
• 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
• LEEK R, GRIMES DR, HARRIS AL and MCINTYRE A, 2016. Methods: Using Three-Dimensional Culture (Spheroids) as an In Vitro Model of Tumour Hypoxia. Advances in experimental medicine and biology. 899, 167-96
• GRIMES DR, KANNAN P, MCINTYRE A, KAVANAGH A, SIDDIKY A, WIGFIELD S, HARRIS A and PARTRIDGE M, 2016. The Role of Oxygen in Avascular Tumor Growth. PloS one. 11(4), e0153692
• MCINTYRE A and HARRIS AL, 2015. Metabolic and hypoxic adaptation to anti-angiogenic therapy: a target for induced essentiality. EMBO molecular medicine. 7(4), 368-379
• TAPMEIER, THOMAS T., MOSHNIKOVA, ANNA, BEECH, JOHN, ALLEN, DANNY, KINCHESH, PAUL, SMART, SEAN, HARRIS, ADRIAN, MCINTYRE, ALAN, ENGELMAN, DONALD M., ANDREEV, OLEG A., RESHETNYAK, YANA K. and MUSCHEL, RUTH J., 2015. The pH low insertion peptide pHLIP Variant 3 as a novel marker of acidic malignant lesions PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 112(31), 9710-9715
• GALLAGHER FA, SLADEN H, KETTUNEN MI, SERRAO EM, RODRIGUES TB, WRIGHT A, GILL A, MCGUIRE S, BOOTH TC, BOREN J, MCINTYRE A, MILLER JL, LEE S, HONESS D, DAY SE, HU D, HOWAT WJ, HARRIS AL and BRINDLE KM, 2015. Carbonic anhydrase activity monitored in vivo by hyperpolarized 13C-magnetic resonance spectroscopy demonstrate its importance for pH regulation in tumors. Cancer research.
• IOANNA LEDAKI*, ALAN MCINTYRE*, SIMON WIGFIELD, FRANCESCA BUFFA, SIMON MCGOWAN, DILAIR BABAN and JI-LIANG LI, 2015. Carbonic anhydrase IX induction defines a heterogeneous cancer cell response to hypoxia and mediates stem cell-like properties and sensitivity to HDAC inhibition. Oncotarget. 6(23), 19413-19427
• SNELL, C. E., TURLEY, H., MCINTYRE, A., LI, D., MASIERO, M., SCHOFIELD, C. J., GATTER, K. C., HARRIS, A. L. and PEZZELLA, F., 2014. Proline-hydroxylated hypoxia-inducible factor 1alpha (HIF-1alpha) upregulation in human tumours: PLoS One PLoS One. 9(2), e88955
• HARJES, U., BRIDGES, E., MCINTYRE, A., FIELDING, B. A. and HARRIS, A. L., 2014. Fatty acid-binding protein 4, a point of convergence for angiogenic and metabolic signaling pathways in endothelial cells: J Biol Chem J Biol Chem. 289(33), 23168-76
• WAGHORN, PHILIP A., JONES, MICHAEL W., MCINTYRE, ALAN, INNOCENTI, ALESSIO, VULLO, DANIELA, HARRIS, ADRIAN L., SUPURAN, CLAUDIU T. and DILWORTH, JONATHAN R., 2012. Targeting Carbonic Anhydrases with Fluorescent BODIPY-Labelled Sulfonamides: European Journal of Inorganic Chemistry European Journal of Inorganic Chemistry. 2012(17), 2898-2907
• TONELLI, R., MCINTYRE, A., CAMERIN, C., WALTERS, Z. S., DI LEO, K., SELFE, J., PURGATO, S., MISSIAGLIA, E., TORTORI, A., RENSHAW, J., ASTOLFI, A., TAYLOR, K. R., SERRAVALLE, S., BISHOP, R., NANNI, C., VALENTIJN, L. J., FACCINI, A., LEUSCHNER, I., FORMICA, S., REIS-FILHO, J. S., AMBROSINI, V., THWAY, K., FRANZONI, M., SUMMERSGILL, B., MARCHELLI, R., HRELIA, P., CANTELLI-FORTI, G., FANTI, S., CORRADINI, R., PESSION, A. and SHIPLEY, J., 2012. Antitumor activity of sustained N-myc reduction in rhabdomyosarcomas and transcriptional block by antigene therapy: Clin Cancer Res Clin Cancer Res. 18(3), 796-807
• MCINTYRE, A., PATIAR, S., WIGFIELD, S., LI, J. L., LEDAKI, I., TURLEY, H., LEEK, R., SNELL, C., GATTER, K., SLY, W. S., VAUGHAN-JONES, R. D., SWIETACH, P. and HARRIS, A. L., 2012. Carbonic anhydrase IX promotes tumor growth and necrosis in vivo and inhibition enhances anti-VEGF therapy: Clin Cancer Res Clin Cancer Res. 18(11), 3100-11
• FAVARO, E., BENSAAD, K., CHONG, M. G., TENNANT, D. A., FERGUSON, D. J., SNELL, C., STEERS, G., TURLEY, H., LI, J. L., GUNTHER, U. L., BUFFA, F. M., MCINTYRE, A. and HARRIS, A. L., 2012. Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells: Cell Metab Cell Metab. 16(6), 751-64
• GILBERT, D. C., MCINTYRE, A., SUMMERSGILL, B., MISSIAGLIA, E., GODDARD, N. C., CHANDLER, I., HUDDART, R. A. and SHIPLEY, J., 2011. Minimum regions of genomic imbalance in stage I testicular embryonal carcinoma and association of 22q loss with relapse: Genes Chromosomes Cancer Genes Chromosomes Cancer. 50(3), 186-95
• GILBERT, D. C., CHANDLER, I., SUMMERSGILL, B., MCINTYRE, A., MISSIAGLIA, E., GODDARD, N. C., HUDDART, R. A. and SHIPLEY, J., 2011. Genomic gain and over expression of CCL2 correlate with vascular invasion in stage I non-seminomatous testicular germ-cell tumours: Int J Androl Int J Androl. 34(4 Pt 2), e114-21; discussion e121
• DUBOIS, L., PEETERS, S., LIEUWES, N. G., GEUSENS, N., THIRY, A., WIGFIELD, S., CARTA, F., MCINTYRE, A., SCOZZAFAVA, A., DOGNE, J. M., SUPURAN, C. T., HARRIS, A. L., MASEREEL, B. and LAMBIN, P., 2011. Specific inhibition of carbonic anhydrase IX activity enhances the in vivo therapeutic effect of tumor irradiation: Radiother Oncol Radiother Oncol. 99(3), 424-31
• NOEL, E. E., YESTE-VELASCO, M., MAO, X., PERRY, J., KUDAHETTI, S. C., LI, N. F., SHARP, S., CHAPLIN, T., XUE, L., MCINTYRE, A., SHAN, L., POWLES, T., OLIVER, R. T., YOUNG, B. D., SHIPLEY, J., BERNEY, D. M., JOEL, S. P. and LU, Y. J., 2010. The association of CCND1 overexpression and cisplatin resistance in testicular germ cell tumors and other cancers: Am J Pathol Am J Pathol. 176(6), 2607-15
• GODDARD, N. C., MCINTYRE, A., GILBERT, D., KITAZAWA, S. and SHIPLEY, J., 2010. No evidence for V600E BRAF mutation in the seminoma cell line TCam-2: Genes, Chromosomes and Cancer Genes, Chromosomes and Cancer. 49(10), 963-966
• GILBERT, D. C., CHANDLER, I., MCINTYRE, A., GODDARD, N. C., GABE, R., HUDDART, R. A. and SHIPLEY, J., 2009. Clinical and biological significance of CXCL12 and CXCR4 expression in adult testes and germ cell tumours of adults and adolescents: J Pathol 217(1), 94-102
• STOOP, H., HONECKER, F., VAN DE GEIJN, G. J. M., GILLIS, A. J. M., COOLS, M. C., DE BOER, M., BOKEMEYER, C., WOLFFENBUTTEL, K. P., DROP, S. L. S., DE KRIJGER, R. R., DENNIS, N., SUMMERSGILL, B., MCINTYRE, A., SHIPLEY, J., OOSTERHUIS, J. W. and LOOIJENGA, L. H. J., 2008. Stem cell factor as a novel diagnostic marker for early malignant germ cells: The Journal of Pathology The Journal of Pathology. 216(1), 43-54
• MCINTYRE, A., GILBERT, D., GODDARD, N., LOOIJENGA, L. and SHIPLEY, J., 2008. Genes, chromosomes and the development of testicular germ cell tumors of adolescents and adults: Genes Chromosomes Cancer Genes Chromosomes Cancer. 47(7), 547-57
• MCINTYRE, A., SUMMERSGILL, B., LU, Y. J., MISSIAGLIA, E., KITAZAWA, S., OOSTERHUIS, J. W., LOOIJENGA, L. H. and SHIPLEY, J., 2007. Genomic copy number and expression patterns in testicular germ cell tumours: Br J Cancer Br J Cancer. 97(12), 1707-12
• GODDARD, N. C., MCINTYRE, A., SUMMERSGILL, B., GILBERT, D., KITAZAWA, S. and SHIPLEY, J., 2007. KIT and RAS signalling pathways in testicular germ cell tumours: new data and a review of the literature: Int J Androl Int J Androl. 30(4), 337-48; discussion 349
• LOOIJENGA, L. H., HERSMUS, R., GILLIS, A. J., PFUNDT, R., STOOP, H. J., VAN GURP, R. J., VELTMAN, J., BEVERLOO, H. B., VAN DRUNEN, E., VAN KESSEL, A. G., PERA, R. R., SCHNEIDER, D. T., SUMMERSGILL, B., SHIPLEY, J., MCINTYRE, A., VAN DER SPEK, P., SCHOENMAKERS, E. and OOSTERHUIS, J. W., 2006. Genomic and expression profiling of human spermatocytic seminomas: primary spermatocyte as tumorigenic precursor and DMRT1 as candidate chromosome 9 gene: Cancer Res Cancer Res. 66(1), 290-302
• MCINTYRE, A., SUMMERSGILL, B., GRYGALEWICZ, B., GILLIS, A. J., STOOP, J., VAN GURP, R. J., DENNIS, N., FISHER, C., HUDDART, R., COOPER, C., CLARK, J., OOSTERHUIS, J. W., LOOIJENGA, L. H. and SHIPLEY, J., 2005. Amplification and overexpression of the KIT gene is associated with progression in the seminoma subtype of testicular germ cell tumors of adolescents and adults: Cancer Res Cancer Res. 65(18), 8085-9
• MCINTYRE, ALAN, SUMMERSGILL, BRENDA, SPENDLOVE, HAYLEY E., HUDDART, ROBERT, HOULSTON, RICHARD and SHIPLEY, JANET, 2005. Activating Mutations and/or Expression Levels of Tyrosine Kinase Receptors GRB7, RAS, and BRAF in Testicular Germ Cell Tumors: Neoplasia Neoplasia. 7(12), 1047-1052
• LU, YONG-JIE, YANG, JINSHU, NOEL, ELODIE, SKOULAKIS, SPYROS, CHAPLIN, TRACY, RAGHAVAN, MANOJ, PURKIS, TRISHA, MCINTYRE, ALAN, KUDAHETTI, SAKUNTHALA C., NAASE, MAHMOUD, BERNEY, DAN, SHIPLEY, JANET, OLIVER, R. TIMOTHY D. and YOUNG, BRYAN D., 2005. Association between Large-scale Genomic Homozygosity without Chromosomal Loss and Nonseminomatous Germ Cell Tumor Development: Cancer Res Cancer Res. 65(20), 9137-9141
• MCINTYRE, A., SUMMERSGILL, B., JAFER, O., RODRIGUEZ, S., ZAFARANA, G., OOSTERHUIS, J. W., GILLIS, A. J., LOOIJENGA, L., COOPER, C., HUDDART, R., CLARK, J. and SHIPLEY, J., 2004. Defining minimum genomic regions of imbalance involved in testicular germ cell tumors of adolescents and adults through genome wide microarray analysis of cDNA clones: Oncogene Oncogene. 23(56), 9142-7