Mirnezami, Alex - University of Southampton

个人简介

He completed his medical degree at the University of Southampton in 1995, having previously obtained a first class BSc as an intercalated student in 1994. His medical training involved various junior surgical positions within the Wessex region and he obtained his membership of The Royal College of Surgeons of England in 1999. He re-joined the University in 2000 as an MRC Clinical Research Training Fellow working in Dr Jeremy Blaydes’ lab, and was awarded his PhD in 2004. He was appointed to a Cancer Research UK Clinician Scientist position in 2008 and commenced as Consultant Surgeon and Senior Lecturer in 2009. He became an Associate Professor in Surgery in 2014 and was appointed to a personal chair in Surgical Oncology in 2015. He has been a visiting fellow at a number of Comprehensive Cancer Centres including the Mayo Clinic in Rochester; The MD Anderson Cancer Centre; and the City of Hope Comprehensive Cancer Centres in the USA; and The Catharina Ziekenhuis Hospital, Eindhoven, in the Netherlands. His work is divided between the laboratory and the main hospital.

研究领域

Colorectal cancer (CRC) is a major public health issue and represents the second most common cause of cancer related death in Europe. Metastases are the principle cause of death in CRC and occur in up to 1 in 4 patients at initial presentation and additionally affect 50% of patients who undergo “curative” surgical resection. The vast majority of patients with CRC metastases remain incurable and can expect a median survival of less than 2 years even with the most advanced biological therapies available. These results highlight the pressing need to identify new molecular targets for the inhibition and treatment of metastases in CRC. Our goal is to identify novel molecular targets in colorectal cancer initiation and progression through a molecular dissection of pathogenic pathways operating in cancer cells. One pathway identified previously involves regulation of the p53 tumour suppressor protein in epithelial cancers. Working in Dr Blaydes’ group, I was able to demonstrate that the transcriptional co-repressor CtBP2 interacts with the Hdm2 onco-protein. Recruitment of the CtBP2 co-repressor by Hdm2 results in a promoter selective repression of p53 dependent transcription. This effect is diminished under hypoxic conditions through a presumed NADH-induced conformational change in the CtBP2 molecule, preventing the Hdm2-CtBP2 interaction. Current work is focused on the identification of microRNAs (miRNAs) involved in colorectal carcinogenesis both within the cancer cells and more importantly within the Tumour microenvironment. MiRNAs represent a fascinating class of small regulatory RNA molecules that play important roles in key cellular processes such as differentiation, metabolism, proliferation, and survival. Several lines of evidence currently indicate an involvement of miRNAs in human carcinogenesis. MiRNA expression is deregulated in several human cancers, and over 50% of miRNA genes are located within or close to chromosomally fragile sites, regions of loss of heterozygosity, amplification, and breakpoints associated with carcinogenesis. Many oncogenes and tumour suppressor genes are believed to be regulated by miRNAs, and it is likely that a fuller dissection of the cellular and molecular pathways controlled by miRNAs will provide new insights into tumorigenic mechanisms in colorectal cancer. In addition, we also undertake clinical research into focused aspects of colorectal cancer disease behaviour and management, including being Chief investigator and local Principal investigator for several national studies on the NCRI portfolio.

近期论文

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Translational aspects in targeting the stromal tumour microenvironment: from bench to bedside - Bhome, Rahul, Al Saihati, Hajir, Goh, Rebecca, Bullock, Marc, Primrose, John, Thomas, Gareth, Sayan, Abdulkadir and Mirnezami, Alexander Published:2016Publication:New Horizons in Translational MedicineVolume:3, (1)Page Range:9-21doi:10.1016/j.nhtm.2016.03.001PMID:27275004 A subset of myofibroblastic cancer-associated fibroblasts regulate collagen fiber elongation, which is prognostic in multiple cancers - Hanley, Christopher J., Noble, Fergus, Ward, Matthew, Bullock, Marc, Drifka, Cole, Mellone, Massimiliano, Manousopoulou, Antigoni, Johnston, Harvey E., Hayden, Annette, Thirdborough, Stephen, Liu, Yuming, Smith, David M., Mellows, Toby, Kao, W. John, Garbis, Spiros D., Mirnezami, Alexander, Underwood, Tim J., Eliceiri, Kevin W and Thomas, Gareth J. Published:2015Publication:OncotargetVolume:7, (5)Page Range:6159-6174doi:10.18632/oncotarget.6740PMID:26716418 A top-down view of the tumor microenvironment: structure, cells and signaling - Bhome, Rahul, Bullock, Marc D., Al Saihati, Hajir A., Goh, Rebecca W., Primrose, John N., Sayan, A. Emre and Mirnezami, Alex H. Published:2015Publication:Frontiers in Cell and Developmental BiologyVolume:3Page Range:33-[9pp]doi:10.3389/fcell.2015.00033PMID:26075202 miR-19-mediated inhibition of transglutaminase-2 leads to enhanced invasion and metastasis in colorectal cancer - Cellura, D., Pickard, K., Quaratino, S., Parker, H., Strefford, J.C., Thomas, G.J., Mitter, R., Mirnezami, A.H. and Peake, N.J. Published:2015Publication:Molecular Cancer ResearchVolume:13, (7)Page Range:1095-1105doi:10.1158/1541-7786.MCR-14-0466PMID:25934693