Edinburgh Research Explorer

Prof Mark Arends

Chair of Pathology

Biography

Mark Arends trained in Medicine (MBChB with Honours) and Pathology (BSc with Honours and PhD) at the University of Edinburgh, becoming a Senior Lecturer in 1995 in the Edinburgh University Department of Pathology and Honorary Consultant at the Royal Infirmary of Edinburgh (MRCPath & FRCPath).

He moved to the University of Cambridge (MA) in January 1999, where he was a University Reader in Histopathology and an Honorary Consultant at Addenbrooke's Hospital, Cambridge. There he was a specialist gastrointestinal and gynaecological pathologist, was lead pathologist in colorectal pathology, gynaecological pathology and bowel cancer screening pathology for Cambridge and East of England.

In July 2013 he moved to University of Edinburgh as Professor of Pathology, Head of the Division of Pathology and co-director of the Centre for Comparative Pathology. His research includes the genomic, genetic and epigenetic mechanisms of colorectal cancer and gynaecological cancer development and progression, including inherited susceptibility to colorectal and endometrial carcinogenesis and in vivo models of intestinal and other tumour formation.

Research Interests

My research interests include identification and validation of new genes involved in formation and progression of cancers, particularly colorectal cancer and the gynaecological cancers as well as other neoplasms. This involves analysis of human cancer samples, cultured cells and in vivo model systems using both comparative pathology and systems pathology approaches. Carcinogenesis involves cellular transit from normal via precursor lesions to malignant neoplasms. These transitions are usually associated with characteristic genetic changes, in the bowel these include alterations to APC (>80%), the DNA mismatch repair genes MLH1 & MSH2 (~15%), KRAS (~40%), and TP53 (~60%) amongst others, and these genes also influence the regulation of proliferation, differentiation and apoptosis.

High throughput array and DNA sequencing analyses have identified genes that consistently show loss or gain of copy number in colorectal tumours including BRUNOL4, PARK2 and IRS2 as new genes in colorectal cancer development and progression. Sleeping Beauty transposition studies have been used to identify new tumour-related genes, including those that cooperate with mutated APC in intestinal tumour formation. DNA methylation studies of epigenetic silencing of cancer-related genes demonstrated involvement of MLH1, MGMT, PTEN, DNMT3B and others in the WNT/APC/B-CATENIN signalling pathway. In vivo models of intestinal tumourigenesis were used to determine contributions to tumour formation by mutant KRAS, RASSF1A, GNAS, PARK2, NRBP1 and others. Use of knockout models validated SLX4/FANCP as a new Fanconi Anaemia gene. The Fanconi DNA repair pathway was shown to be critically important in repairing aldehyde-induced DNA damage thus protecting against tumour formation.

 

Websites

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