Dr Colin Steele - Advanced Colorectal Cancer
Introduction
Research Fellow, Senior Clinical Lecturer in Colorectal Surgery
Honorary Consultant Surgeon, Glasgow Royal Infirmary
Colorectal cancer patients die as a result of metastatic progression or disease recurrence following surgery. Though surgery can cure some patients of colorectal cancer with liver limited disease, the vast majority cannot be treated effectively. Current systemic therapies offer modest survival benefits. Understanding the mechanisms of metastatic progression in the most aggressive forms of colorectal cancer will permit therapeutic targeting in the future alongside surgery to improve outcomes for my patients.
My current research interests focus on the immune microenvironment of locally advanced and metastatic colorectal cancer. We have identified the importance of common white blood cells – neutrophils – in driving metastatic progression in models of cancer. Using state-of-the-art in vivo models and human specimens, I am currently seeking to understand the interactions between neutrophil populations, other immune cells and tumour cells in driving progression of colorectal cancer. This work will help to identify vulnerabilities in the immune system that may be harnessed with immunotherapies to target more aggressive colorectal cancer. My clinical work at Glasgow Royal Infirmary operating on patients with locally advanced rectal cancer provides an opportunity to interact with this patient group, obtain relevant clinical samples and help prioritise my research.
Other funding:
Biography
Education and qualifications
2019: Intercollegiate FRCS.
2015: PhD: Investigating the role of CXCR2 signalling in pancreatic inflammation and cancer. College of Medical, Veterinary and Life Sciences. University of Glasgow. Supervisor: Professor Owen Sansom.
2009: Intercollegiate MRCS (RCPSG)
2004: BSc Med Sci, Clinical Medicine, University of Glasgow. Supervisor: Dr Ann-Marie McNicol
1996: MBChB,University of Glasgow.
Appointments
2017-present: NES/CSO Clinical Lectureship
2011–2014: Wellcome Trust Clinical Research Fellow
2010–2011: Lister Fellow Glasgow Royal Infirmary August
Recent Publications
2024
Fetit R, McLaren A, White M, Mills ML, Falconer J, Cortes-Lavaud X, Gilroy K, Lannagan TR, Ridgway RA, Nixon C, Naiker V, Njunge R, Clarke CJ, Whyte D, Kirschner K, Jackstadt R, Norman JC, Carlin LM, Campbell AD, Sansom OJ, Steele CW. Characterising neutrophil subtypes in cancer using scRNA sequencing demonstrates the importance of IL-1β/CXCR2 axis in generation of metastasis specific neutrophils. Cancer Res Commun. 2024.
Pennel KAF, Hatthakarnkul P, Wood CS, Lian GY, Al-Badran SSF, Quinn JA, Legrini A, Inthagard J, Alexander PG, van Wyk H, Kurniawan A, Hashmi U, Gillespie MA, Mills M, Ammar A, Hay J, Andersen D, Nixon C, Rebus S, Chang DK, Kelly C, Harkin A, Graham J, Church D, Tomlinson I, Saunders M, Iveson T, Lannagan TRM, Jackstadt R, Maka N, Horgan PG, Roxburgh CSD, Sansom OJ, McMillan DC, Steele CW, Jamieson NB, Park JH, Roseweir AK, Edwards J. JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors. J Exp Clin Cancer Res. 2024;43(1):64.
Whyte D, Voorde JV, Sumpton D, Dhayade S, Dornier E, Moore M, Novo D, Peters J, Wiesheu R, Mackey JBG, McFarlane AJ, Fercoq F, Fisher S, Caballero CD, Gilroy K, Redmond KL, Mitchell LE, Anderson E, Thomson G, Dzierozynski LN, Saab JJA, Lewis CA, Muir A, Halbrook CJ, Strathdee D, Jackstadt R, Nixon C, Dunne P, Steele CW, Carlin LM, Macpherson IR, Roberts EW, Coffelt SB, Blyth K, Sansom OJ, Norman JC, Clarke CJ. Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung. bioRxiv. 2024:2024.2007.2002.601676.
2023
Fetit R, White M, Mills ML, Cortes-Lavaud X, McLaren A, Falconer J, Gilroy K, Nixon C, Kirschner K, Jackstadt R, Campbell AD, Sansom OJ, Steele CW. Characterising neutrophil subtypes in cancer using human and murine single-cell RNA sequencing datasets. bioRxiv. 2023;Volume:2023.2007.2013.548820.
McLaren AS, Fetit R, Wood CS, Falconer J, Steele CW. Single cell sequencing of neutrophils demonstrates phenotypic heterogeneity and functional plasticity in health, disease, and cancer. Chin Clin Oncol. 2023;10.21037/cco-22-121.
McMahon RK, O'Cathail SM, Nair H, Steele CW, Platt JJ, Digby M, McDonald AC, Horgan PG, Roxburgh CSD. The neoadjuvant rectal score and a novel magnetic resonance imaging based neoadjuvant rectal score are stage independent predictors of long-term outcome in locally advanced rectal cancer. Colorectal Dis. 2023;10.1111/codi.16667.
Wood CS, Pennel KAF, Leslie H, Legrini A, Cameron AJ, Melissourgou-Syka L, Quinn JA, van Wyk HC, Hay J, Roseweir AK, Nixon C, Roxburgh CSD, McMillan DC, Biankin AV, Sansom OJ, Horgan PG, Edwards J, Steele CW, Jamieson NB. Spatially Resolved Transcriptomics Deconvolutes Prognostic Histological Subgroups in Patients with Colorectal Cancer and Synchronous Liver Metastases. Cancer Res. 2023;83:1329-1344.
2022
Pennel KA, Quinn JA, Nixon C, Inthagard J, van Wyk HC, Chang D, Rebus S, Hay J, Maka NN, Roxburgh CS, Horgan PG, McMillan DC, Park JH, Roseweir AK, Steele CW, Edwards J. CXCL8 expression is associated with advanced stage, right sidedness, and distinct histological features of colorectal cancer. J Pathol Clin Res. 2022;8:509-520
Persson P, Chong P, Steele CW, Quinn M. Prevention and management of complications in pelvic exenteration. Eur J Surg Oncol. 2022; 48:2277-2283.
Gould LE, Pring ET, Drami I, Moorghen M, Naghibi M, Jenkins JT, Steele CW, Roxburgh CS. A systematic review of the pathological determinants of outcome following resection by pelvic exenteration of locally advanced and locally recurrent rectal cancer. Int J Surg. 2022;104:106738.
2021
Han J, Tao M, Wu X, Li D, Ma Y, Dawood S, Steele CW, Tan KK, Wang Q. Reporting quality of practice guidelines on colorectal cancer: evaluation using the RIGHT reporting checklist. Ann Transl Med. 2021;9(14):1175.
Mackey JBG, McFarlane AJ, Jamieson T, Jackstadt R, Raffo-Iraolagoitia XL, Secklehner J, Cortes-Lavaud X, Fercoq F, Clarke W, Hedley A, Gilroy K, Lilla S, Vuononvirta J, Graham GJ, De Filippo K, Murphy DJ, Steele CW, Norman JC, Bird TG, Mann DA, Morton JP, Zanivan S, Sansom OJ, Carlin LM. Maturation, developmental site, and pathology dictate murine neutrophil function. bioRxiv. 2021.
Galbraith NJ, Wood C, Steele CW. Targeting Metastatic Colorectal Cancer with Immune Oncological Therapies. Cancers (Basel). 2021;13(14).
Gillespie MA, Steele CW, Lannagan TRM, Sansom OJ, Roxburgh CSD. Pre-clinical modelling of rectal cancer to develop novel radiotherapy-based treatment strategies. Oncol Rev. 2021;15:511.
McSorley ST, Steele CW, Anderson JH, McKinlay S. Comment on 'Preoperative intravenous iron therapy and survival after colorectal cancer surgery: long-term results from the IVICA randomized controlled trial'. Colorectal Dis. 2021;23(2):555-556.
2020
Bisset CN, Carter B, Law J, Hewitt J, Parmar K, Moug SJ; ELF Study Group Collaborative Authorship. The influence of social media on recruitment to surgical trials. BMC Med Res Methodol. 2020;20:201.
Carter B, Law J, Hewitt J, Parmar KL, Boyle JM, Casey P, Maitra I, Pearce L, Moug SJ; ELF Study Group. Association between preadmission frailty and care level at discharge in older adults undergoing emergency laparotomy. Br J Surg. 2020;107:218-226.
CRC COVID Research Collaborative. The impact of the COVID-19 pandemic on colorectal cancer service provision. Br J Surg. 2020; 107:e521–e522.
McSorley ST, Anderson JH, Whittle T, Roxburgh CS, Horgan PG, McMillan DC, Steele CW. The impact of preoperative systemic inflammation on the efficacy of intravenous iron infusion to correct anaemia prior to surgery for colorectal cancer. Perioperative Med 2020;9:17
McSorley ST, Tham A, Dolan RD, Steele CW, Ramsingh J, Roxburgh C, Horgan PG, McMillan DC. Perioperative Blood Transfusion is Associated with Postoperative Systemic Inflammatory Response and Poorer Outcomes Following Surgery for Colorectal Cancer. Ann Surg Oncol. 2020 Mar;27(3):833-843
Steele CW, Whittle T, Smith JJ. Review: KRAS mutations are influential in driving hepatic metastases and predicting outcome in colorectal cancer. Chin Clin Oncol. 2019 Oct;8(5):53.
2019
Golder AM, Steele CW, Conn D, MacKay GJ, McMillan DC, Horgan PG, Roxburgh CS, McSorley ST. Effect of preoperative oral antibiotics in combination with mechanical bowel preparation on inflammatory response and short-term outcomes following left-sided colonic and rectal resections. BJS Open. 2019;3:830-839.
Jackstadt R, van Hooff SR, Leach JD, Cortes-Lavaud X, Lohuis JO, Ridgway RA, Wouters VM, Roper J, Kendall TJ, Roxburgh CS, Horgan PG, Nixon C, Nourse C, Gunzer M, Clark W, Hedley A, Yilmaz OH, Rashid M, Bailey P, Biankin AV, Campbell AD, Adams DJ, Barry ST, Steele CW, Medema JP, Sansom OJ. Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis. Cancer Cell. 2019;36:319-336.e7.
McSorley S, Johnstone M, Steele CW, Roxburgh CSD, McMillan D, Horgan P, Mansouri D. Normocytic anaemia is associated with systemic inflammation and poorer survival in patients with colorectal cancer treated with curative intent. International Journal of Colorectal Disease 2019;34:401-408.
McSorley S, Tham A, Steele CW, Dolan R, Horgan P, McMillan D. Quantitative data on red cell measures of iron status and their relation to the magnitude of the systemic inflammatory response and survival in patients with colorectal cancer. EJSO 2019 Feb 27. pii: S0748-7983(19)30300-2.
Parmar KL, Law J, Carter B, Hewitt J, Boyle JM, Casey P, Maitra I, Farrell IS, Pearce L, Moug SJ; ELF Study Group. Frailty in Older Patients Undergoing Emergency Laparotomy: Results From the UK Observational Emergency Laparotomy and Frailty (ELF) Study. Ann Surg. 2019; 273: 709-718
Reader CS, Vallath S, Steele CW, Haider S, Brentnall A, Desai A, Moore KM, Jamieson NB, Chang D, Bailey P, Scarpa A, Lawlor R, Chelala C, Keyse SM, Biankin A, Morton JP, Evans TRJ, Barry ST, Sansom OJ, Kocher HM, Marshall JF. The integrin αvβ6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy. J Pathol. 2019;249:332-342.
2018
McSorley S, Steele CW, McMahon A. Meta-analysis of oral antibiotics in combination with mechanical bowel preparation the day before surgery to reduce surgical site infections in elective colorectal surgery. BJS (Open) 2018; 2:185-194.
Lab Members
Postdoctoral Scientist
Sarah Ressel
S.Ressel@crukscotlandinstitute.ac.uk
I am a postdoctoral researcher in the Steele lab since 2024. My current research focusses on characterising neutrophils subtypes in the metastatic environment in colorectal cancer and how the different subtypes influence disease progression. Before joining the CRUK Scotland institute, I worked on a variety of different projects ranging from the biochemical characterisation of bacterial proteins to small non-coding RNAs in respiratory virus infections. Outside the lab I enjoy exploring the Scottish Highlands.
Senior Scientific Officer
John Falconer
J.Falconer@crukscotlandinstitute.ac.uk
I joined The Steele Lab Group in The CRUK Scotland Institute as a Senior Scientific Officer in 2021. During that time, I have mostly been focusing on the effects of diet and targeted radiotherapy on colorectal cancer outcome. Prior to this appointment, I was involved with research on adaptive immune cell interaction in the context of demyelinating diseases. In my free time I enjoy lawn care, rail timetable compilation and Formula 1.
Clinical Research Fellows
Alistair McLaren
Alistair.McLaren@glasgow.ac.uk
I am a TRACC Clinical Research Fellow currently taking a pause in training in Medical Oncology to pursue a PhD. My interests lie in cancer resistance to immunotherapy, and my PhD focuses on the role of neutrophils in the immune microenvironment of advanced colorectal cancer, particularly in liver metastases, and whether neutrophils can be manipulated to play a positive “anti-tumour” role. Outside of research I enjoy travel, food and watching and playing a variety of sports.
Chia Kong
Ross McMahon
Colin Wood
Liam Henderson
Graduate Students
Lydia Melissourgou-Syka
Natalie Peckett