High-Content Analysis Resource

Introduction

Head: Emma Shanks

Shanks EThe Screening Facility couples genetic and chemical high throughput screening with multiparametric phenotypic image analysis to support translational cancer research. We employ functional genomics (siRNA, shRNA, CRISPR) tools in both pooled and arrayed approaches to support target identification and target validation in multiple types of cancer. Our state-of-the-art image analysis capabilities, including a machine learning module, support identification of a suite of cellular phenotypes in both 2D and 3D environments.

The Head and Neck Cancer Research Group aims to identify novel therapeutic targets for treating non-HPV associated HNSCC, specifically oral squamous cell carcinomas. We focus on target identification and validation using cell lines derived directly from patient tumours, and a suite of in vitro and in vivo techniques. Central to our approach is the multiplexing of functional genomics and drug screening, genomic characterisation and patient data to identify the strongest candidates for clinical progression: development of radiosensitising agents and those effective under hypoxia is a key focus. We are supported by external collaborations with a number of HNSCC radiobiologists, surgeons and oncologists.

 
Other funding:
 
                   CRUK Glasgow Centre

Lab Report

icon Functional Screening Report

Key Publications

Shanks E, Ketteler R, Ebner D. Academic drug discovery within the United Kingdom: a reassessment. Nat Rev Drug Discov 14: 510, 2015

Shanks EJ, Ong HB, Robinson DA, Thompson S, Sienkiewicz N, Fairlamb AH, Frearson JA. Development and validation of a cytochrome c-coupled assay for pteridine reductase 1 and dihydrofolate reductase. Analytical Biochemistry 396, 194–203, 2010

Recent Publications

2018

Lee JS, Das A, Jerby-Arnon L, Arafeh R, Auslander N, Davidson M, McGarry L, James D, Amzallag A, Park SG, Cheng K, Robinson W, Atias D, Stossel C, Buzhor E, et al. Harnessing synthetic lethality to predict the response to cancer treatment. Nat Commun 2018;9(1):2546. doi: 10.1038/s41467-018-04647-1

2017

Cairney CJ, Godwin LS, Bilsland AE, Burns S, Stevenson KH, McGarry L, Revie J, Moore JD, Wiggins CM, Collinson RS, Mudd C, Tsonou E, Sadaie M, Bennett DC, Narita M, Torrance CJ, Keith WN. A 'synthetic-sickness' screen for senescence re-engagement targets in mutant cancer backgrounds. PLoS Genet 2017; 13: e1006942

Mitchell R, Hopcroft LEM, Baquero P, Allan EK, Hewit K, James D, Hamilton G, Mukhopadhyay A, O'Prey J, Hair A, Melo JV, Chan E, Ryan KM, Maguer-Satta V, Druker BJ, Clark RE, Mitra S, Herzyk P, Nicolini FE, Salomoni P, Shanks E, Calabretta B, Holyoake TL, Helgason GV. Targeting BCR-ABL-Independent TKI Resistance in Chronic Myeloid Leukemia by mTOR and Autophagy Inhibition. J Natl Cancer Inst. 2017 Nov 20. doi: 10.1093/jnci/djx236. [Epub ahead of print]

Davidson MA, Shanks EJ. 3q26-29 Amplification in head and neck squamous cell carcinoma: a review of established and prospective oncogenes. FEBS J 2017; 284: 2705-31

2016

Peck B, Schug ZT, Zhang Q, Dankworth B, Jones DT, Smethurst E, Patel R, Mason S, Jiang M, Saunders R, Howell M, Mitter R, Spencer-Dene B, Stamp G, McGarry L, James D, Shanks E, Aboagye EO, Critchlow SE, Leung HY, Harris AL, Wakelam MJO, Gottlieb E, Schulze A. Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments. Cancer Metab 2016; 4: 6

2015

Mardilovich K, Baugh M, Crighton D, Kowalczyk D, Gabrielsen M, Munro J, Croft DR, Lourenco F, James D, Kalna G, McGarry L, Rath O, Shanks E, Garnett MJ, McDermott U, Brookfield J, Charles M, Hammonds T, Olson MF. LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation. Oncotarget 2015. doi: 10.18632/oncotarget.6288. Epub 2015 Nov 3

Mardilovich K, Gabrielsen M, McGarry L, Orange C, Patel R, Shanks E, Edwards J, Olson MF. Elevated LIM kinase 1 in non-metastatic prostate cancer reflects its role in facilitating androgen receptor nuclear translocation. Mol Cancer Ther 14: 246-58, 2015

Miller BW, Morton JP, Pinese M, Saturno G, Jamieson NB, McGhee E, Timpson P, Leach J, McGarry L, Shanks E, Bailey P, Chang D, Oien K, Karim S, Au A, Steele C, Carter CR, McKay C, Anderson K, Evans TR, Marais R, Springer C, Biankin A, Erler JT, Sansom OJ. Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy. EMBO Mol Med 7: 1063-76, 2015

Schug ZT, Peck B, Jones DT, Zhang Q, Grosskurth S, Alam IS, Goodwin LM, Smethurst E, Mason S, Blyth K, McGarry L, James D, Shanks E, Kalna G, Saunders RE, Jiang M, Howell M, Lassailly F, Thin MZ, Spencer-Dene B, Stamp G, van den Broek NJ, Mackay G, Bulusu V, Kamphorst JJ, Tardito S, Strachan D, Harris AL, Aboagye EO, Critchlow SE, Wakelam MJ, Schulze A, Gottlieb E. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell  27: 57-71, 2015

Shanks E, Ketteler R, Ebner D. Academic drug discovery within the United Kingdom: a reassessment. Nat Rev Drug Discov 14: 510, 2015

2014

Jerby-Arnon L, Pfetzer N, Waldman YY, McGarry L, James D, Shanks E, Seashore-Ludlow B, Weinstock A, Geiger T, Clemons PA, Gottlieb E, Ruppin E. Predicting cancer-specific vulnerability via data-driven detection of synthetic lethality. Cell 158: 1199-209, 2014

Shanks EJ. Strategic siRNA screening approaches to target cancer at the Cancer Research UK Beatson Institute. Comb Chem High Throughput Screen 17: 328-32, 2014

Group Members

Shanks lab 046 cropped

Principal Scientific Officer

Lynn McGarry

Post-doc

Grant A. McGregor

Data Manager

Daniel James

Technician

Eric Kalkman (CRUK Glasgow Centre)

PhD Student

Matthew Davidson

Research

At the bench 3 160

Read more about the Research Groups working at the Beatson Institute.

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Seminars

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Find out more about our seminars including our Distinguished Seminar Programme.

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