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:

Lab 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

2017

Gundry C, Marco S, Rainero E, Miller B, Dornier E, Mitchell L, Caswell P, Campbell A, Hogeweg A, Sansom OJ, Morton JP & Norman JC (2017) Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion. Nat Commun. Epub. 15 March 2017.

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, Anderson M, Fink JL, Holmes O, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Mead RS, Xu Q, Wu J, Pinese M, Cowley MJ, Jones MD, Nagrial AM, Chin VT, Chantrill LA, Mawson A, Chou A, Scarlett CJ, Pinho AV, Rooman I, Giry-Laterriere M, Samra JS, Kench JG, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, McKay CJ, Carter CR, Dickson EJ, Graham JS, Duthie F, Oien K, Hair J, Morton JP, Sansom OJ, Grutzmann R, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Schulick RD, Wolfgang CL, Morgan RA, Lawlor RT, Rusev B, Corbo V, Salvia R, Cataldo I, Tortora G, Tempero MA, Australian Pancreatic Cancer Genome I, Hofmann O, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Gill AJ, Pearson JV, Grimmond SM, Waddell N & Biankin AV (2017) Hypermutation In Pancreatic Cancer. Gastroenterology. 152, 68-74.

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

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 (2017) ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth. EMBO Mol Med. 9, 198-218.

Ritschka B, Storer M, Mas A, Heinzmann F, Ortells MC, Morton JP, Sansom OJ, Zender L & Keyes WM (2017) The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes Dev. 1, 172-183.

Rosenfeldt MT, O'Prey J, Flossbach L, Nixon C, Morton JP, Sansom OJ & Ryan KM (2017) PTEN deficiency permits the formation of pancreatic cancer in the absence of autophagy. Cell Death Differ. 24, 1303-1304.

Harris NL, Vennin C, Conway JR, Vine KL, Pinese M, Cowley MJ, Shearer RF, Lucas MC, Herrmann D, Allam AH, Pajic M, Morton JP, APGI, Biankin AV, Ranson M, Timpson P & Saunders DN (2017) SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer. Oncogene. 36, 4288-4298.

Vennin C, Chin VT, Warren SC, Lucas MC, Herrmann D, Magenau A, Melenec P, Walters SN, del Monte-Nieto G, Conway JRW, Nobis M, Allam AH, McCloy RA, Currey N, Pinese M, Boulghourjian A, Zaratzian A, Adam AAS, Heu C, Nagrial AM, Chou A, Steinmann A,
 Drury A, Froio D, Giry-Laterriere M, Harris NLE, Phan T, Jain R, Weninger W, McGhee EJ, Whan R, Johns AL, Samra JS, Chantrill L, Gill AJ, Kohonen-Corish M, Harvey RP, Biankin AV, Australian Pancreatic Cancer Genome Initiative (APGI), Evans TRJ, Anderson KI, Grey ST, Ormandy CJ, Gallego-Ortega D, Wang Y, Samuel MS, Sansom OJ, Burgess A, Cox TRMorton JP, Pajic M & Timpson P. (2017) Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis. Sci Transl Med. 9, 384.

Rice AJ, Cortes E, Lachowski D, Cheung BCH, Karim SA, Morton JP & Del Río Hernández A. (2017) Matrix stiffness induces epithelial-mesenchymal transition and promotes chemoresistance in pancreatic cancer cells. Oncogenesis 6, e352.

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-Léon S, Colombe A, Valantin J, Gadot N, Servoz E, Morton J, Goddard I, Couvelard A, Rebours V, Guillermet J, Sansom OJ, Treilleux I, Valcourt U, Sentis S, Dubus P & Bartholin L. (2017) Acinar-to-Ductal Metaplasia Induced by Transforming Growth Factor Beta Facilitates KRASG12D-driven Pancreatic Tumorigenesis. Cell Mol Gastroenterol Hepatol. 4, 263-282.

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.

2013

Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, Athineos D, Kang TW, Lasitschka F, Andrulis M, Pascual G, Morris KJ, Khan S, Jin H, Dharmalingam G, Snijders AP, Carroll T, Capper D, Pritchard C, Inman GJ, Longerich T, Sansom OJ, Benitah SA, Zender L & Gil J (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 15, 978-90.

Denley SM, Jamieson NB, McCall P, Oien KA, Morton JP, Carter CR, Edwards J & McKay CJ (2013) Activation of the IL-6R/Jak/stat pathway is associated with a poor outcome in resected pancreatic ductal adenocarcinoma. J Gastrointest Surg. 17, 887-98.

Karim SA, Creedon H, Patel H, Carragher NO, Morton JP, Muller WJ, Evans TR, Gusterson B, Sansom OJ & Brunton VG (2013) Dasatinib inhibits mammary tumour development in a genetically engineered mouse model. J Pathol. 230, 430-40.

Morton JP & Sansom OJ (2013) MYC-y mice: from tumour initiation to therapeutic targeting of endogenous MYC. Mol Oncol. 7, 248-58.

Muller PA, Trinidad AG, Timpson P, Morton JP, Zanivan S, van den Berghe PV, Nixon C, Karim SA, Caswell PT, Noll JE, Coffill CR, Lane DP, Sansom OJ, Neilsen PM, Norman JC & Vousden KH (2013) Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene. 32, 1252-65.

Nobis M, Carragher NO, McGhee EJ, Morton JP, Sansom OJ, Anderson KI & Timpson P (2013) Advanced intravital subcellular imaging reveals vital three-dimensional signalling events driving cancer cell behaviour and drug responses in live tissue. FEBS J. 280, 5177-97.

Nobis M, McGhee EJ, Morton JP, Schwarz JP, Karim SA, Quinn J, Edward M, Campbell AD, McGarry LC, Evans TR, Brunton VG, Frame MC, Carragher NO, Wang Y, Sansom OJ, Timpson P & Anderson KI (2013) Intravital FLIM-FRET imaging reveals dasatinib-induced spatial control of src in pancreatic cancer. Cancer Res. 73, 4674-86.

Rosenfeldt MT, O'Prey J*, Morton JP*, Nixon C, MacKay G, Mrowinska A, Au A, Rai TS, Zheng L, Ridgway R, Adams PD, Anderson KI, Gottlieb E, Sansom OJ & Ryan KM (2013) p53 status determines the role of autophagy in pancreatic tumour development. Nature. 504, 296-300.

Steele CW, Jamieson NB, Evans TR, McKay CJ, Sansom OJ, Morton JP & Carter CR (2013) Exploiting inflammation for therapeutic gain in pancreatic cancer. Br J Cancer. 108, 997-03.

2012

Blyth K, Morton JP & Sansom OJ (2012) The right time, the right place: will targeting human cancer-associated mutations to the mouse provide the perfect preclinical model? Curr Opin Genet Dev. 22, 28-35.

Dozynkiewicz MA, Jamieson NB, Macpherson I, Grindlay J, van den Berghe PV, von Thun A, Morton JP, Gourley C, Timpson P, Nixon C, McKay CJ, Carter R, Strachan D, Anderson K, Sansom OJ, Caswell PT & Norman JC (2012) Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression. Dev Cell. 22, 131-45.

Jamieson NB, Morran DC, Morton JP, Ali A, Dickson EJ, Carter CR, Sansom OJ, Evans TR, McKay CJ & Oien KA (2012) MicroRNA Molecular Profiles Associated with Diagnosis, Clinicopathologic Criteria, and Overall Survival in Patients with Resectable Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 8, 534-45.

Lab Members

Post-docs

Karen Pickering (Precision Panc)
Mathias Tesson

Scientific Officers

Curtis Rink
Loveena Rishi Delori (CRUK Glasgow Centre)

PhD Students

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

morton group 2

Research

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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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