Medicine

Alex Mirnezami

BSc BM PhD PCME FRCS (England)

Primary position:
Senior Lecturer in Surgery
Other positions:
Cancer Research UK Clinician Scientist

Background

The University of Southampton

Alex Mirnezami is a Senior Lecturer and Consultant Surgeon in the department of surgery, with a specialist interest in the field of colorectal surgery. 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 doctor posts 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, working within the laboratory group headed by Professor Graham Packham. His work is divided between the laboratory and the main hospital. 

Qualifications

BSc (First Class Honours), Biomedical Sciences, University of Southampton 1994
BM, University of Southampton 1995
PhD, University of Southampton 2004
PCME, University of Wales College of Medicine 2007
FRCS, Royal College of Surgeons of England, 2009

Appointments held

Cancer Research UK Clinician Scientist in Surgery
Senior Lecturer and Consultant Colorectal Surgeon
Southampton University Hospital NHS Trust

ACPGBI Colorectal Fellowship - Leeds General Infirmary

Clinical Lecturer in Surgery
University of Southampton
2006-2009

Wessex Higher Surgical Training Programme
- Basingstoke Hospital
- Southampton General Hospital
- Portsmouth Hospital
- Poole Hospital
2003-2006

MRC Clinical Research Training Fellowship
2000-2003

Wessex Basic Surgical Training Programme
- Bournemouth Hospital
- Poole Hospital
- Southampton Hospital
1997-2000

Anatomy Demonstrator
University of Southampton
1996-1997

Mr Alex Mirnezami's photo

Publications

The University of Southampton's electronic library (e-prints)

Article

Zhang, L., Pickard, K., Bullock, M.D., Jenei, V., Strefford, J., Mitter, R., Kelly, G., Primrose, J.N., Thomas, G., Packham, G.K. and Mirnezami, A.H. (2013) miR-153 supports colorectal cancer progression via pleiotropic effects that enahance invasion and chemotherapeutic resistance. Cancer Research, 73, 6435-6447. (doi:10.1158/0008-5472.CAN-12-3308). (PMID:23950211).
Bullock, M.D., Bruce, A., Sreekumar, R., Curtis , N, Cheung, T., Reading, Isabel, Primrose, J.N., Ottensmeier, C., Packham, G.K., Thomas, G. and Mirnezami, A.H. (2013) FOXO3 expression during colorectal cancer progression: Biomarker potential reflects a tumour suppressor role. British Journal of Cancer, 109, (2), 387-394. (doi:10.1038/bjc.2013.355). (PMID:23828518).
Bullock, M.D., Pickard, Karen M., Nielsen, B.S, Sayan, A.E., Jenei, Veronika, Mellone, Max, Mitter, R., Primrose, J.N., Thomas, Gareth J., Packham, Graham and Mirnezami, Alex H. (2013) Pleiotropic actions of mIR-21 highlight the critical role of deregulated stromal microRNA's during colorectal cancer progression. Cell Death and Disease, 4, e684. (doi:10.1038/cddis.2013.213). (PMID:23788041).
Bullock, M.D., Pickard, K.M., Nielsen, B.S., Sayan, A.E., Jenei, V., Mellone, M., Mitter, B., Primrose, J.N., Thomas, G.J., Packham, G.K. and Mirnezami, A.H. (2013) Pleiotropic actions of miR-21 highlight the critical role of deregulated stromal microRNAs during colorectal cancer progression. Cell Death and Disease, 4, e684. (doi:10.1038/cddis.2013.213). (PMID:23788041).
Zhang, L., Pickard, Karen M., Thomas, Gareth J., Packham, Graham and Mirnezami, A.H. (2013) miR-153 supports colorectal cancer progression via pleiotropic effects that enhance invasion and chemotherapy resistance. Cancer Research, 73, 6435. (doi:10.1158/0008-5472.CAN-12-3308 ).
Curtis, N. J., Primrose, J. N., Thomas, G. J., Mirnezami, A. H. and Ottensmeier, C. H. (2012) The adaptive immune response to colorectal cancer: from the laboratory to clinical practice. European Journal of Surgical Oncology, 38, (10), 889-896. (doi:10.1016/j.ejso.2012.05.011). (PMID:22721580).
Vaughan-Shaw, P.G., Cheung, T., Knight, J.S., Nichols, P.H., Pilkington, S.A. and Mirnezami, A.H. (2012) A prospective case–control study of extralevator abdominoperineal excision (ELAPE) of the rectum versus conventional laparoscopic and open abdominoperineal excision: comparative analysis of short-term outcomes and quality of life. Techniques in Coloproctology, 16, (5), 355-362. (doi:10.1007/s10151-012-0851-4). (PMID:22777690).
Vaughan-Shaw, P.G., King, A.T., Cheung, T., Beck, N.E., Knight, J.S., Nichols, P.H., Nugent, K.P., Pilkington, S.A., Smallwood, J.A. and Mirnezami, A.H. (2011) Early experience with laparoscopic extralevator abdominoperineal excision within an enhanced recovery setting: analysis of short-term outcomes and quality of life. Annals of The Royal College of Surgeons of England, 93, (6), 451-459. (doi:10.1308/003588411X588621). (PMID:21929915).
Mirnezami, Alexander, Mirnezami, Reza, Chandrakumaran, Kandiah, Sasapu, Kishore, Sagar, Peter and Finan, Paul (2011) Increased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis. Annals of Surgery, 253, (5), 890-899. (doi:10.1097/SLA.0b013e3182128929). (PMID:21394013).
Mirnezami, Reza, Mirnezami, Alexander H., Chandrakumaran, Kandiah, Abu Hilal, Mohammad, Pearce, Neil W., Primrose, John N. and Sutcliffe, Robert P. (2011) Short- and long-term outcomes after laparoscopic and open hepatic resection: systematic review and meta-analysis. HPB, 13, (5), 295-308. (doi:10.1111/j.1477-2574.2011.00295.x). (PMID:21492329).
Mirnezami, A.H., Sagar, P.M., Kavanagh, D., Witherspoon, P., Lee, P. and Winter, D. (2010) Clinical algorithms for the surgical management of locally recurrent rectal cancer. Diseases of the Colon & Rectum, 53, (9), 1248-57.
Mirnezami, A.H., Fenn , C., Phillips, N., Eardley, I. and Sagar , P.M. (2010) Surgery for recurrent rectal cancer: technical notes and management of complications. Techniques in Coloproctology (In Press).
Mirnezami, A.H., Moran, B.J. and Cecil, T.D. (2009) Sugarbaker procedure for Pseudomyxoma Peritonei. Techniques in Coloproctology, 13, (4), 373-374. (doi:10.1007/s10151-009-0513-3).
Bandyopadhyay, D., Sagar, P.M., Mirnezami, A., Lengyel, J., Morrison, C. and Gatt, M. (2009) Laparoscopic resection for recurrent Crohn's disease: safety, feasibility and short-term outcomes. Colorectal Disease, 13, (2), 161-65. (doi:10.1111/j.1463-1318.2009.02100.x).
Mirnezami, A.H., Gonsalves, S., Gatt, M. and Sagar, P.M. (2009) Ileal pouch-vaginal fistula: treatment with the new surgisis biodesign fistula plug. Techniques in Coloproctology, 13, (3), 259-260. (doi:10.1007/s10151-009-0516-0).
Zeidan, Bashar A., Cutress, Ramsey I., Hastie, Claire, Mirnezami, Alex H., Packham, Graham and Townsend, Paul A. (2009) SELDI-TOF MS Proteomics in Breast Cancer. Clinical Proteomics, 5, (3-4), 133-147. (doi:10.1007/s12014-009-9032-5).
Mirnezami, A., Pilkington, S., Monga, A. and Nugent, K.P. (2008) Multidisciplinary team meetings for pelvic floor disorders. Colorectal Disease, 10, (4), 413pp. (doi:10.1111/j.1463-1318.2008.01513.x).
Mirnezami, A. H. F, Pickard, K., Zhang, L., Primrose, J. N. and Packham, G. (2008) MicroRNAs: key players in carcinogenesis and novel therapeutic targets. European Journal of Surgical Oncology, 35, (4), 339-347. (doi:10.1016/j.ejso.2008.06.006).
Bergman, Lee M., Morris, Laila, Darley, Matthew, Mirnezami, Alexander H., Gunatilake, Samal C. and Blaydes, Jeremy P. (2006) Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins. BMC Cell Biology, 7, (35) (doi:10.1186/1471-2121-7-35).
Mirnezami, Alexander H., Campbell, Sandra J., Darley, Matthew, Primrose, John N., Johnson, Peter W.M. and Blaydes, Jeremy P. (2003) Hdm2 recruits a hypoxia-sensitive corepressor to negatively regulate p53-dependent transcription. Current Biology, 13, (14), 1234-1239. (doi:10.1016/S0960-9822(03)00454-8).
Tisi, P.V., Mirnezami, A., Baker, S., Tawn, J., Parvin, S.D. and Darke, S.G. (2002) Role of subintimal angioplasty in the treatment of chronic lower limb ischaemia. European Journal of Vascular and Endovascular Surgery, 24, (5), 417-422. (doi:10.1053/ejvs.2002.1754).
 

Research

Research Interests

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. MiRNAs represent a fascinating and recently identified 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.

Academic unit:  Cancer Sciences

Responsibilities

Supervisor and examiner of 4th year student projects, Intercalated projects, and PhD students.

Third year students Surgery attachment coordinator.

Chief investigator for two NIHR portfolio studies on colorectal cancer and Peritoneal surface malignancies.

Contact

Mr Alex Mirnezami
Phone: (023) 8079 5170
Email: ahm@soton.ac.uk