Medicine

Alex Mirnezami

BSc BM PhD PCME FRCS (England)

Primary position:
Professor of Surgical Oncology
Other positions:
Consultant General and Colorectal Surgeon

Background

The University of Southampton

Alex Mirnezami is Professor of Surgical Oncology and Consultant Surgeon in the Department of Surgery, with a specialist interest in the field of Colorectal Surgery, and in particular advanced and recurrent colorectal cancer.

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.

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

Professor of Surgical Oncology and Consultant General and Colorectal Surgeon
University of Southampton and University Hospital Southampton Foundation Trust
2015

Associate Professor in Surgery and Consultant General and Colorectal Surgeon
University of Southampton and University Hospital Southampton Foundation Trust
2014-2015

Cancer Research UK Clinician Scientist in Surgery
Senior Lecturer and Consultant Colorectal Surgeon
University of Southampton and University Hospital Southampton Foundation Trust
2009-2014

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

Professor Alex Mirnezami's photo

Publications

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

Article

Chand, Manish, Siddiqui, Muhammed R.S., Gupta, Ashish, Rasheed, Shahnawaz, Tekkis, Paris, Parvaiz, Amjad, Mirnezami, Alex H. and Qureshi, Tahseen (2014) Systematic review of emergent laparoscopic colorectal surgery for benign and malignant disease. World Journal of Gastroenterology, 20, (45), 16956-16963. (doi:10.3748/wjg.v20.i45.16956). (PMID:25493008).
Mirnezami, Reza, Moran, Brendan J., Harvey, Kate, Cecil, Tom, Chandrakumaran, Kandiah, Carr, Norman, Mohamed, Faheez and Mirnezami, Alexander H. (2014) Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases. World Journal of Gastroenterology, 20, (38), 14018-14032. (doi:10.3748/wjg.v20.i38.14018). (PMID:25320542).
Mirnezami, R., Mehta, A.M., Chandrakumaran, K., Cecil, T., Moran, B.J., Carr, N., Verwaal, V.J., Mohamed, F. and Mirnezami, A.H. (2014) Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone. British Journal of Cancer, 111, (8), 1500-1508. (doi:10.1038/bjc.2014.419). (PMID:25225906).
Bullock, Marc D., Mellone, Max, Pickard, Karen M., Sayan, Abdulkadir Emre, Mitter, Richard, Primrose, John N., Packham, Graham K., Thomas, Gareth and Mirnezami, Alexander H. (2014) Molecular profiling of the invasive tumor microenvironment in a 3-dimensional model of colorectal cancer cells and ex vivo fibroblasts. Journal of Visualized Experiments, 86 (doi:10.3791/51475). (PMID:24836208).
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 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.

Academic unit:  Cancer Sciences Academic Unit

Affiliate academic units:  Clinical and Experimental Sciences Academic Units

Responsibilities

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

Genomics England local lead for colorectal cancer.

Peer review and Editorial service for a variety of Clinical and Scientific Journals.

Grant review service for national and international award bodies.

Expert committee member for clinical and scientific review panels.

Specialist Adviser to NICE and CQC.

Clinical practice focused on colorectal surgery, and colorectal cancer in particular.

Supervisor and examiner for:

  • Undergraduate 4th year student BMedSci and MMedSci projects
  • Postgraduate MD and PhD students

Third year students Surgery attachment co-coordinator.

Teaching Responsibilities

Undergraduate teaching:

Years 1-2:

  • Medicine in Practice year 1 hospital teacher.
  • Think tank poster assessor and small group tutorials on the GIT for 2nd year students and BM4 students.
  • Large group seminars on General Surgical topics,

Year 3:

  • Year 3 General Surgery Course Co-coordinator for the region
  • Year 3 Steering group member
  • BM Intermediate Examination Working group
  • Administration and organisation of Suturing skills workshop for third year students.
  • End of attachment examiner for 3rd year Medical students.
  • Year 3 Assignment marker.
  • Organisation and delivery of teaching in colorectal surgery to final year students.

Year 4:

  • Project supervisor and examiner for 4th year students' projects – 6 students supervised in last two academic years, with one achieveing a first class and award for best project report.

Year 5:

  • Ward based teaching for final year medical students.
  • Clinical Supervision of final year students.
  • Mini CEX examiner for attachment students.

All Years:

  • Part of the revalidation steering group for development and implementation of the new medical curriculum for the University of Southampton.

Postgraduate teaching:

Small group seminars for Foundation Year trainees and more informal teaching prior to examinations on the wards. Supervision of Academic foundation year and academic clinical fellows in surgery.

Contact

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

Email: A.H.Mirnezami@soton.ac.uk