Jennifer Morton - Preclinical Precision Pancreas

Introduction

morton j

Every year around 340,000 people die of pancreatic cancer worldwide, and by 2030 pancreatic cancer is predicted to be the second commonest cause of cancer death in the western world. Most patients present too late for surgery with aggressive invasive or metastatic disease. Current chemotherapies offer little benefit, however, so we urgently need to better understand the disease and identify better options for clinicians and patients.

To do this, we model different genetic subsets of the disease in genetically engineered models. These models mimic human tumours in terms of genes altered, and also because they develop a dense desmoplastic stroma of fibroblasts, stellate cells, immune cells, and extracellular matrix proteins such as collagen.

By studying our models, we can determine the importance of specific genetic and transcriptomic changes identified in human tumours, identify novel targets for therapy, both in tumour cells and in the microenvironment, and test new therapies pre-clinically.

See the following CRUK blogs for more details about Dr Morton's work:

Other funding:

Precision Panc logoPancreatic Cancer UK logo

   CRUK Glasgow Centre

Lab Report

icon Preclinical Precision Pancreas Report

Key Publications

Steele CW, Karim SA, Leach JD, Bailey P, Upstill-Goddard R, Rishi L, Foth M, Bryson S, McDaid K, Wilson Z, Eberlein C, Candido JB, Clarke M, Nixon C, Connelly J, Jamieson N, Carter CR, Balkwill F, Chang DK, Evans TR, Strathdee D, Biankin AV, Nibbs RJ, Barry ST, Sansom OJ & Morton JP (2016) CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. 29, 832-45.

Driscoll DR, Karim SA, Sano M, Gay DM, Jacob W, Yu J, Mizukami Y, Gopinathan A, Jodrell DI, Evans TR, Bardeesy N, Hall MN, Quattrochi BJ, Klimstra DS, Barry ST, Sansom OJ, Lewis BC & Morton JP (2016) mTORC2 Signaling Drives the Development and Progression of Pancreatic Cancer. Cancer Res. 76, 6911-23.

Steele CW, Karim SA, Foth M, Rishi L, Leach JD, Porter RJ, Nixon C, Jeffry Evans TR, Carter CR, Nibbs RJ, Sansom OJ & Morton JP (2015) CXCR2 inhibition suppresses acute and chronic pancreatic inflammation. J Pathol. 237, 85-97.

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 (2015) 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.

Morran DC, Wu J, Jamieson NB, Mrowinska A, Kalna G, Karim SA, Au AY, Scarlett CJ, Chang DK, Pajak MZ, Australian Pancreatic Cancer Genome I, Oien KA, McKay CJ, Carter CR, Gillen G, Champion S, Pimlott SL, Anderson KI, Evans TR, Grimmond SM, Biankin AV, Sansom OJ & Morton JP (2014) Targeting mTOR dependency in pancreatic cancer. Gut. 63, 1481-9.

Biography

Education and qualifications

2001: PhD, Veterinary Pathology, University of Glasgow
1998: BSc (Hons. 1st), Medical Biochemistry, University of Glasgow

Appointments

2015-present: Preclinical trials coordinator, Cancer Research UK Glasgow Centre
2010-present: Associate Scientist, Cancer Research UK Beatson Institute, Glasgow, UK
2007-2010: Postdoctoral Research Associate, Institute of Cancer Sciences, University of Glasgow, UK
2004-2007: Postdoctoral Research Fellow, University of Massachusetts Medical School, Worcester, USA
2001-2004: Postdoctoral Research Assistant, Institute of Biomedical & Life Sciences, University of Glasgow, UK

Recent Publications

2018

Godfrey JD, Morton JP, Wilczynska A, Sansom OJ, Bushell MD. MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus. Cell Death Dis. 2018;9: 644.

2017

Chou A, Froio D, Nagrial AM, Parkin A, Murphy KJ, Chin VT, Wohl D, Steinmann A, Stark R, Drury A, Walters SN, Vennin C, Burgess A, Pinese M, Chantrill LA, Cowley MJ, Molloy TJ, Australian Pancreatic Cancer Genome I, Waddell N, Johns A et al. Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer. Gut 2017 Oct 28. pii: gutjnl-2017-315144. doi: 10.1136/gutjnl-2017-315144. [Epub ahead of print]

Chuvin N, Vincent DF, Pommier RM, Alcaraz LB, Gout J, Caligaris C, Yacoub K, Cardot V, Roger E, Kaniewski B, Martel S, Cintas C, Goddard-Leon S, Colombe A, Valantin J, Gadot N, Servoz E, Morton J, Goddard I, Couvelard A et al. Acinar-to-Ductal Metaplasia Induced by Transforming Growth Factor Beta Facilitates KRAS(G12D)-driven Pancreatic Tumorigenesis. Cell Mol Gastroenterol Hepatol 2017; 4: 263-82

Conway JRW, Vennin C, Cazet AS, Herrmann D, Murphy KJ, Warren SC, Wullkopf L, Boulghourjian A, Zaratzian A, Da Silva AM, Pajic M, Morton JP, Cox TR, Timpson P (2017) Three-dimensional organotypic matrices from alternative collagen sources as pre-clinical models for cell biology. Sci Rep 7: 16887

Farrell AS, Joly MM, Allen-Petersen BL, Worth PJ, Lanciault C, Sauer D, Link J, Pelz C, Heiser LM, Morton JP, Muthalagu N, Hoffman MT, Manning SL, Pratt ED, Kendsersky ND, Egbukichi N, Amery TS, Thoma MC, Jenny ZP, Rhim AD et al. MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance. Nat Commun 2017; 8: 1728

Gundry C, Marco S, Rainero E, Miller B, Dornier E, Mitchell L, Caswell PT, Campbell AD, Hogeweg A, Sansom OJ, Morton JP, Norman JC. Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion. Nat Commun 2017; 8: 14646

Harris NL, Vennin C, Conway JR, Vine KL, Pinese M, Cowley MJ, Shearer RF, Lucas MC, Herrmann D, Allam AH, Pajic M, Morton JP, Australian Pancreatic Cancer Genome I, Biankin AV, Ranson M, Timpson P, Saunders DN. SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer. Oncogene 2017; 36: 4288-98

Humphris JL, Patch AM, Nones K, Bailey PJ, Johns AL, McKay S, Chang DK, Miller DK, Pajic M, Kassahn KS, Quinn MC, Bruxner TJ, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Stone A, Wilson PJ et al. Hypermutation In Pancreatic Cancer. Gastroenterology 2017; 152: 68-74.e2

Nobis M, Herrmann D, Warren SC, Kadir S, Leung W, Killen M, Magenau A, Stevenson D, Lucas MC, Reischmann N, Vennin C, Conway JRW, Boulghourjian A, Zaratzian A, Law AM, Gallego-Ortega D, Ormandy CJ, Walters SN, Grey ST, Bailey J et al. A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts. Cell Rep 2017; 21: 274-88

Rath N, Morton JP, Julian L, Helbig L, Kadir S, McGhee EJ, Anderson KI, Kalna G, Mullin M, Pinho AV, Rooman I, Samuel MS, Olson MF. ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth. EMBO Mol Med 2017; 9: 198-218

Rice AJ, Cortes E, Lachowski D, Cheung BCH, Karim SA, Morton JP, Del Rio Hernandez A. Matrix stiffness induces epithelial-mesenchymal transition and promotes chemoresistance in pancreatic cancer cells. Oncogenesis 2017; 6: e352

Ritschka B, Storer M, Mas A, Heinzmann F, Ortells MC, Morton JP, Sansom OJ, Zender L, Keyes WM. The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev 2017; 31: 172-83

Rosenfeldt MT, O'Prey J, Flossbach L, Nixon C, Morton JP, Sansom OJ, Ryan KM. PTEN deficiency permits the formation of pancreatic cancer in the absence of autophagy. Cell Death Differ 2017; 24: 1303-4

Vennin C, Chin VT, Warren SC, Lucas MC, Herrmann D, Magenau A, Melenec P, Walters SN, Del Monte-Nieto G, Conway JR, Nobis M, Allam AH, McCloy RA, Currey N, Pinese M, Boulghourjian A, Zaratzian A, Adam AA, Heu C, Nagrial AM et al. Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci Transl Med 2017; 9: pii: eaai8504

Leach JDG, Morton JP, Sansom OJ. Neutrophils: homing in on the myeloid mechanisms of metastasis. Mol Immunol 2017; 9: 832-45

Morton JP, Sansom OJ. CXCR2 inhibition in pancreatic cancer: opportunities for immunotherapy? Immunotherapy 2017; 9: 9-12

Vennin C, Murphy M, Morton JP, Cox TR, Pajic M, Timpson P. Reshaping the Tumor Stroma as a New Approach for Treatment of Pancreatic Cancer. Gastroenterology 2017 Dec 26. pii: S0016-5085(17)36738-0. doi: http://dx.doi.org/10.1053/j.gastro.2017.11.280. [Epub ahead of print]

2016

Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grutzmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM, Australian Pancreatic Cancer Genome Initiative, Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV & Grimmond SM (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 531, 47-52.

Driscoll DR, Karim SA, Sano M, Gay DM, Jacob W, Yu J, Mizukami Y, Gopinathan A, Jodrell DI, Evans TR, Bardeesy N, Hall MN, Quattrochi BJ, Klimstra DS, Barry ST, Sansom OJ, Lewis BC & Morton JP (2016) mTORC2 Signaling Drives the Development and Progression of Pancreatic Cancer. Cancer Res. 76, 6911-23.

Erami Z, Herrmann D, Warren SC, Nobis M, McGhee EJ, Lucas MC, Leung W, Reischmann N, Mrowinska A, Schwarz JP, Kadir S, Conway JR, Vennin C, Karim SA, Campbell AD, Gallego-Ortega D, Magenau A, Murphy KJ, Ridgway RA, Law AM, Walters SN, Grey ST, Croucher DR, Zhang L, Herzog H, Hardeman EC, Gunning PW, Ormandy CJ, Evans TR, Strathdee D, Sansom OJ, Morton JP, Anderson KI & Timpson P (2016) Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue. Cell Rep. 14, 152-67.

Guest RV, Boulter L, Dwyer BJ, Kendall TJ, Man TY, Minnis-Lyons SE, Lu WY, Robson AJ, Gonzalez SF, Raven A, Wojtacha D, Morton JP, Komuta M, Roskams T, Wigmore SJ, Sansom OJ & Forbes SJ (2016) Notch3 drives development and progression of cholangiocarcinoma. Proc Natl Acad Sci U S A. 113, 12250-5.

Matzke-Ogi A, Jannasch K, Shatirishvili M, Fuchs B, Chiblak S, Morton J, Tawk B, Lindner T, Sansom O, Alves F, Warth A, Schwager C, Mier W, Kleeff J, Ponta H, Abdollahi A & Orian-Rousseau V (2016) Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling. Gastroenterology. 150, 513-25.

Lesina M, Wormann SM, Morton J, Diakopoulos KN, Korneeva O, Wimmer M, Einwachter H, Sperveslage J, Demir IE, Kehl T, Saur D, Sipos B, Heikenwalder M, Steiner JM, Wang TC, Sansom OJ, Schmid RM & Algul H (2016) RelA regulates CXCL1/CXCR2-dependent oncogene-induced senescence in murine Kras-driven pancreatic carcinogenesis. J Clin Invest. 126, 2919-32.

Steele CW, Karim SA, Leach JD, Bailey P, Upstill-Goddard R, Rishi L, Foth M, Bryson S, McDaid K, Wilson Z, Eberlein C, Candido JB, Clarke M, Nixon C, Connelly J, Jamieson N, Carter CR, Balkwill F, Chang DK, Evans TR, Strathdee D, Biankin AV, Nibbs RJ, Barry ST, Sansom OJ & Morton JP (2016) CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. Cancer Cell. 29, 832-45.

2015

Dikovskaya D, Cole JJ, Mason SM, Nixon C, Karim SA, McGarry L, Clark W, Hewitt RN, Sammons MA, Zhu J, Athineos D, Leach JD, Marchesi F, van Tuyn J, Tait SW, Brock C, Morton JP, Wu H, Berger SL, Blyth K & Adams PD (2015) Mitotic Stress Is an Integral Part of the Oncogene-Induced Senescence Program that Promotes Multinucleation and Cell Cycle Arrest. Cell Rep. 12, 1483-96.

Gopinathan A, Morton JP, Jodrell DI & Sansom OJ (2015) GEMMs as preclinical models for testing pancreatic cancer therapies. Dis Model Mech. 8, 1185-200.

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 (2015) 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.

Steele CW, Karim SA, Foth M, Rishi L, Leach JD, Porter RJ, Nixon C, Jeffry Evans TR, Carter CR, Nibbs RJ, Sansom OJ & Morton JP (2015) CXCR2 inhibition suppresses acute and chronic pancreatic inflammation. J Pathol. 237, 85-97.

2014

Herrmann D, Conway JR, Vennin C, Magenau A, Hughes WE, Morton JP & Timpson P (2014) Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment. Carcinogenesis. 35, 1671-9.

Ali A, Brown V, Denley S, Jamieson NB, Morton JP, Nixon C, Graham JS, Sansom OJ, Carter CR, McKay CJ, Duthie FR & Oien KA (2014) Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel. BMC Clin Pathol. 14, 35.

Arjonen A, Kaukonen R, Mattila E, Rouhi P, Hognas G, Sihto H, Miller BW, Morton JP, Bucher E, Taimen P, Virtakoivu R, Cao Y, Sansom OJ, Joensuu H & Ivaska J (2014) Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis. J Clin Invest. 124, 1069-82.

Hamilton G, Abraham AG, Morton J, Sampson O, Pefani DE, Khoronenkova S, Grawenda A, Papaspyropoulos A, Jamieson N, McKay C, Sansom O, Dianov GL & O'Neill E (2014) AKT regulates NPM dependent ARF localization and p53mut stability in tumors. Oncotarget. 5, 6142-67.

Johnsson AK, Dai Y, Nobis M, Baker MJ, McGhee EJ, Walker S, Schwarz JP, Kadir S, Morton JP, Myant KB, Huels DJ, Segonds-Pichon A, Sansom OJ, Anderson KI, Timpson P & Welch HC (2014) The Rac-FRET mouse reveals tight spatiotemporal control of Rac activity in primary cells and tissues. Cell Rep. 6, 1153-64.

Li A, Morton JP, Ma Y, Karim SA, Zhou Y, Faller WJ, Woodham EF, Morris HT, Stevenson RP, Juin A, Jamieson NB, MacKay CJ, Carter CR, Leung HY, Yamashiro S, Blyth K, Sansom OJ & Machesky LM (2014) Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes. Gastroenterology. 146, 1386-96.

Morran DC, Wu J, Jamieson NB, Mrowinska A, Kalna G, Karim SA, Au AY, Scarlett CJ, Chang DK, Pajak MZ, Australian Pancreatic Cancer Genome I, Oien KA, McKay CJ, Carter CR, Gillen G, Champion S, Pimlott SL, Anderson KI, Evans TR, Grimmond SM, Biankin AV, Sansom OJ & Morton JP (2014) Targeting mTOR dependency in pancreatic cancer. Gut. 63, 1481-9.

Muthalagu N, Junttila MR, Wiese KE, Wolf E, Morton J, Bauer B, Evan GI, Eilers M & Murphy DJ (2014) BIM is the primary mediator of MYC-induced apoptosis in multiple solid tissues. Cell Rep. 8, 1347-53.

Nobis M, McGhee EJ, Herrmann D, Magenau A, Morton JP, Anderson KI & Timpson P (2014) Monitoring the dynamics of Src activity in response to anti-invasive dasatinib treatment at a subcellular level using dual intravital imaging. Cell Adh Migr. 8, 478-86.

Tan EH*, Morton JP*, Timpson P, Tucci P, Melino G, Flores ER, Sansom OJ, Vousden KH & Muller PA (2014) Functions of TAp63 and p53 in restraining the development of metastatic cancer. Oncogene. 33, 3325-33.

Walz S, Lorenzin F, Morton J, Wiese KE, von Eyss B, Herold S, Rycak L, Dumay-Odelot H, Karim S, Bartkuhn M, Roels F, Wustefeld T, Fischer M, Teichmann M, Zender L, Wei CL, Sansom O, Wolf E & Eilers M (2014) Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles. Nature. 511, 483-7.

Lab Members

Post-docs

Karen Pickering (CRUK PRECISION-Panc)
Loveena Rishi Delori
Mathias Tesson (CRUK PRECISION-Panc)

Senior Scientific Officers

Saadia Karim
Viola Paulus-Hock (CRUK PRECISION-Panc)

Scientific Officer

Curtis Rink (CRUK Glasgow Centre)

PhD Students

Laura Lapienyte (Pancreatic Cancer UK Future Leaders Academy)
Dale Watt (CRUK Glasgow Centre)

morton group 2

Research

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Seminars

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

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