Prof Jen Morton - Preclinical Pancreatic Cancer
Introduction
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. Furthermore, current chemotherapies offer little benefit, 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 the 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.
EmailSee the following CRUK blogs for more details about Prof Morton's work:
- New trick for 'old' drug brings hope for pancreatic cancer patients
- Scientists tear down pancreatic cancer's defences
Other funding:
Lab Report
pdf Morton Lab Report (1.41 MB)
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
2019-present: Professor, School of Cancer Sciences, University of Glasgow, Glasgow, UK
2019-present: Senior Staff Scientist, Cancer Research UK Scotland Institute, Glasgow, UK
2015-present: Preclinical trials coordinator, Cancer Research UK Glasgow Centre
2010-2019: 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
2024
Astuti Y, Raymant M, Quaranta V, Clarke K, Abudula M, Smith O, Bellomo G, Chandran-Gorner V, Nourse C, Halloran C, Ghaneh P, Palmer D, Jones RP, Campbell F, Pollard JW, Morton JP, Mielgo A, Schmid MC. Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis. Nat Cancer. 2024.
Go S, Demetriou C, Valenzano G, Hughes S, Lanfredini S, Ferry H, Arbe-Barnes E, Sivakumar S, Bashford-Rogers R, Middleton MR, Mukherjee S, Morton J, Jones K, O’Neill E. Tissue-resident NK cells support survival in pancreatic cancer through promotion of cDC1-CD8T activity. bioRxiv. 2024:2023.2010.2014.562332.
Salvador-Barbero B, Alatsatianos M, Morton JP, Sansom OJ, Hogan C. Oncogenic KRAS cells use Wnt signalling and cell dormancy to override homeostatic cell elimination mechanisms in adult pancreas. bioRxiv. 2024:2024.2002.2013.579930.
Tesson M, Stevenson K, Karim SA, Nixon C, Chalmers AJ, Sansom OJ, O'Neil E, Jones K, Morton JP. Targeted irradiation in an autochthonous mouse model of pancreatic cancer. Dis Model Mech. 2024.
2023
Coetzee AS, Carter EP, Rodríguez-Fernández L, Heward J, Wang Q, Karim SA, Boughetane L, Milton C, Uyulur F, Morton JP, Kocher HM, Grose RP. Nuclear FGFR1 promotes pancreatic stellate cell-driven invasion through up-regulation of Neuregulin 1. Oncogene. 2023; 42: 491-500
Conway JRW, Warren SC, Lee YK, McCulloch AT, Magenau A, Lee V, Metcalf XL, Stoehr J, Haigh K, Abdulkhalek L, Guaman CS, Reed DA, Murphy KJ, Pereira BA, Mélénec P, Chambers C, Latham SL, Lenthall H, Deenick EK, Ma Y, Phan T, Lim E, Joshua AM, Walters S, Grey ST, Shi YC, Zhang L, Herzog H, Croucher DR, Philp A, Scheele C, Herrmann D, Sansom OJ, Morton JP, Papa A, Haigh JJ, Nobis M, Timpson P. Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse. Sci Adv. 2023;9:eadf9063.
Fey SK, Najumudeen AK, Ford C, Gilroy K, Upstill-Goddard R, Chang DK, Clark W, Nixon C, Barry ST, Morton JP, Campbell AD, Sansom OJ. Kras loss of heterozygosity promotes MAPK dependent pancreatic ductal adenocarcinoma and induces therapeutic sensitivity. bioRxiv. 2023:2023.2008.2029.552598.
Go S, Demetriou C, Hughes S, Lanfredini S, Valenzano G, Ferry H, Arbe-Barnes E, Sivakumar S, Bashford-Rogers R, Middleton MR, Mukherjee S, Morton J, Jones K, O’Neill E. Tissue-resident NK cells support survival in pancreatic cancer through promotion of cDC1-CD8T activity. bioRxiv. 2023:2023.2010.2014.562332.
Graziano V, Dannhorn A, Hulme H, Williamson K, Buckley H, Karim SA, Wilson M, Lee SY, Kaistha BP, Islam S, Thaventhiran JED, Richards FM, Goodwin R, Brais R, Morton JP, Dovedi SJ, Schuller AG, Eyles J, Jodrell DI. Defining the spatial distribution of extracellular adenosine revealed a myeloid-dependent immunosuppressive microenvironment in pancreatic ductal adenocarcinoma. J Immunother Cancer. 2023;11.
Najumudeen AK, Fey SK, Millett LM, Ford C, Gilroy K, Gunduz N, Ridgway RA, Anderson E, Strathdee D, Clark W, Nixon C, Morton JP, Campbell AD, Sansom OJ. KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo. bioRxiv. 2023:2023.2008.2029.555396.
Perurena N, Lock R, Davis RA, Raghavan S, Pilla NF, Ng R, Loi P, Guild CJ, Miller AL, Sicinska E, Cleary JM, Rubinson DA, Wolpin BM, Gray NS, Santagata S, Hahn WC, Morton JP, Sansom OJ, Aguirre AJ, Cichowski K. USP9X mediates an acute adaptive response to MAPK suppression in pancreatic cancer but creates multiple actionable therapeutic vulnerabilities. Cell Rep Med. 2023;10.1016/j.xcrm.2023.101007:101007.
Whyte D, Skalka G, Walsh P, Wilczynska A, Paul NR, Mitchell C, Nixon C, Clarke W, Bushell M, Morton JP, Murphy DJ, Muthalagu N. NUAK1 governs centrosome replication in pancreatic cancer via MYPT1/PP1β and GSK3β-dependent regulation of PLK4. Mol Oncol. 2023;17:1212-1227
Barry ST, Gabrilovich DI, Sansom OJ, Campbell AD, Morton JP. Therapeutic targeting of tumour myeloid cells. Nat Rev Cancer. 2023; 23: 216–237
Coffelt SB, Morton JP. LOXL2 in pancreatic tumourigenesis: the complexity of tumour-stromal crosstalk exemplified. Gut. 2023;72:221-222.
2022
Ali A, Jamieson NB, Khan IN, Chang D, Giovannetti E, Funel N, Frampton AE, Morton J, Sansom O, Evans TRJ, Duthie F, McKay CJ, Samra J, Gill AJ, Biankin A, Oien KA. Prognostic implications of microRNA-21 overexpression in pancreatic ductal adenocarcinoma: an international multicenter study of 686 patients. Am J Cancer Res. 2022;12:5668-5683.
Bellomo G, Rainer C, Quaranta V, Astuti Y, Raymant M, Boyd E, Stafferton R, Campbell F, Ghaneh P, Halloran CM, Hammond DE, Morton JP, Palmer D, Vimalachandran D, Jones R, Mielgo A, Schmid MC. Chemotherapy-induced infiltration of neutrophils promotes pancreatic cancer metastasis via Gas6/AXL signalling axis. Gut. 2022;
Below CR, Kelly J, Brown A, Humphries JD, Hutton C, Xu J, Lee BY, Cintas C, Zhang X, Hernandez-Gordillo V, Stockdale L, Goldsworthy MA, Geraghty J, Foster L, O'Reilly DA, Schedding B, Askari J, Burns J, Hodson N, Smith DL, Lally C, Ashton G, Knight D, Mironov A, Banyard A, Eble JA, Morton JP, Humphries MJ, Griffith LG, Jørgensen C. A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids. Nat Mater. 2022;21:110-119.
Freckmann EC, Sandilands E, Cumming E, Neilson M, Román-Fernández A, Nikolatou K, Nacke M, Lannagan TRM, Hedley A, Strachan D, Salji M, Morton JP, McGarry L, Leung HY, Sansom OJ, Miller CJ, Bryant DM. Traject3d allows label-free identification of distinct co-occurring phenotypes within 3D culture by live imaging. Nat Commun. 2022;13:5317.
Halbrook CJ, Thurston G, Boyer S, Anaraki C, Jiménez JA, McCarthy A, Steele NG, Kerk SA, Hong HS, Lin L, Law FV, Felton C, Scipioni L, Sajjakulnukit P, Andren A, Beutel AK, Singh R, Nelson BS, Van Den Bergh F, Krall AS, Mullen PJ, Zhang L, Batra S, Morton JP, Stanger BZ, Christofk HR, Digman MA, Beard DA, Viale A, Zhang J, Crawford HC, Pasca di Magliano M, Jorgensen C, Lyssiotis CA. Differential integrated stress response and asparagine production drive symbiosis and therapy resistance of pancreatic adenocarcinoma cells. Nat Cancer. 2022;3:1386-1403.
Kidger AM, Saville MK, Rushworth LK, Davidson J, Stellzig J, Ono M, Kuebelsbeck LA, Janssen KP, Holzmann B, Morton JP, Sansom OJ, Caunt CJ, Keyse SM. Suppression of mutant Kirsten-RAS (KRAS(G12D))-driven pancreatic carcinogenesis by dual-specificity MAP kinase phosphatases 5 and 6. Oncogene. 2022;41:2811–2823
Vaziri-Gohar A, Cassel J, Mohammed FS, Zarei M, Hue JJ, Hajihassani O, Graor HJ, Srikanth YVV, Karim SA, Abbas A, Prendergast E, Chen V, Katayama ES, Dukleska K, Khokhar I, Andren A, Zhang L, Wu C, Erokwu B, Flask CA, Zarei M, Wang R, Rothermel LD, Romani AMP, Bowers J, Getts R, Tatsuoka C, Morton JP, Bederman I, Brunengraber H, Lyssiotis CA, Salvino JM, Brody JR, Winter JM. Limited nutrient availability in the tumor microenvironment renders pancreatic tumors sensitive to allosteric IDH1 inhibitors. Nat Cancer. 2022;3:852-865.
2021
Below CR, Kelly J, Brown A, Humphries JD, Hutton C, Xu J, Lee BY, Cintas C, Zhang X, Hernandez-Gordillo V, Stockdale L, Goldsworthy MA, Geraghty J, Foster L, O'Reilly DA, Schedding B, Askari J, Burns J, Hodson N, Smith DL, Lally C, Ashton G, Knight D, Mironov A, Banyard A, Eble JA, Morton JP, Humphries MJ, Griffith LG, Jørgensen C. A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids. Nat Mater. 2021;21:110–119
Dreyer SB, Upstill-Goddard R, Paulus-Hock V, Paris C, Lampraki E-M, Dray E, Serrels B, Caligiuri G, Rebus S, Plenker D, Galluzzo Z, Brunton H, Cunningham R, Tesson M, Nourse C, Bailey U-M, Jones M, Moran-Jones K, Wright DW, Duthie F, Oien K, Evers L, McKay CJ, McGregor GA, Gulati A, Brough R, Bajrami I, Pettitt S, Dziubinski ML, Candido J, Balkwill F, Barry ST, Grützmann R, Rahib L, Johns A, Pajic M, Froeling FEM, Beer P, Musgrove EA, Petersen GM, Ashworth A, Frame MC, Crawford HC, Simeone DM, Lord C, Mukhopadhyay D, Pilarsky C, Tuveson DA, Cooke SL, Jamieson NB, Morton JP, Sansom OJ, Bailey PJ, Biankin AV, Chang DK. Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer. Gastroenterology. 2021; 160:362-377
Falcomata C, Barthel S, Ulrich A, Diersch S, Veltkamp C, Rad L, Boniolo F, Solar M, Steiger K, Seidler B, Zukowska M, Madej J, Wang M, Ollinger R, Maresch R, Barenboim M, Eser S, Tschurtschenthaler M, Mehrabi A, Roessler S, Goeppert B, Kind A, Schnieke A, Robles MS, Bradley A, Schmid RM, Schmidt-Supprian M, Reichert M, Weichert W, Sansom OJ, Morton JP, Rad R, Schneider G, Saur D. Genetic screens identify a context-specific PI3K/p27Kip1 node driving extrahepatic biliary cancer. Cancer Discov. 2021;11: 3158–3177
Floerchinger A, Murphy KJ, Latham SL, Warren SC, McCulloch AT, Lee YK, Stoehr J, Mélénec P, Guaman CS, Metcalf XL, Lee V, Zaratzian A, Da Silva A, Tayao M, Rolo S, Phimmachanh M, Sultani G, McDonald L, Mason SM, Ferrari N, Ooms LM, Johnsson AE, Spence HJ, Olson MF, Machesky LM, Sansom OJ, Morton JP, Mitchell CA, Samuel MS, Croucher DR, Welch HCE, Blyth K, Caldon CE, Herrmann D, Anderson KI, Timpson P, Nobis M. Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging. Cell Rep. 2021;36(11):109689.
Hill W, Zaragkoulias A, Salvador-Barbero B, Parfitt GJ, Alatsatianos M, Padilha A, Porazinski S, Woolley TE, Morton JP, Sansom OJ, Hogan C. EPHA2-dependent outcompetition of KRASG12D mutant cells by wild-type neighbors in the adult pancreas. Curr Biol. 2021;31:2550-2560
Hutton C, Heider F, Blanco-Gomez A, Banyard A, Kononov A, Zhang X, Karim S, Paulus-Hock V, Watt D, Steele N, Kemp S, Hogg EKJ, Kelly J, Jackstadt RF, Lopes F, Menotti M, Chisholm L, Lamarca A, Valle J, Sansom OJ, Springer C, Malliri A, Marais R, Pasca di Magliano M, Zelenay S, Morton JP, Jørgensen C. Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity. Cancer Cell. 2021; 39: 1227-1244
Latif AL, Newcombe A, Li S, Gilroy K, Robertson NA, Lei X, Stewart HJS, Cole J, Terradas MT, Rishi L, McGarry L, McKeeve C, Reid C, Clark W, Campos J, Kirschner K, Davis A, Lopez J, Sakamaki JI, Morton JP, et al. BRD4-mediated repression of p53 is a target for combination therapy in AML. Nat Commun. 2021;12:241.
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.
Murphy KJ, Reed DA, Vennin C, Conway JRW, Nobis M, Yin JX, Chambers CR, Pereira BA, Lee V, Filipe EC, Trpceski M, Ritchie S, Lucas MC, Warren SC, Skhinas JN, Magenau A, Metcalf XL, Stoehr J, Major G, Parkin A, Bidanel R, Lyons RJ, Zaratzian A, Tayao M, Da Silva A, Abdulkhalek L, Gill AJ, Johns AL, Biankin AV, Samra J, Grimmond SM, Chou A, Goetz JG, Samuel MS, Lyons JG, Burgess A, Caldon CE, Horvath LG, Daly RJ, Gadegaard N, Wang Y, Sansom OJ, Morton JP, Cox TR, Pajic M, Herrmann D, Timpson P. Intravital imaging technology guides FAK-mediated priming in pancreatic cancer precision medicine according to Merlin status. Sci Adv. 2021;7:eabh0363.
Nacke M, Sandilands E, Nikolatou K, Román-Fernández Á, Mason S, Patel R, Lilla S, Yelland T, Galbraith LCA, Freckmann EC, McGarry L, Morton JP, Shanks E, Leung HY, Markert E, Ismail S, Zanivan S, Blyth K, Bryant DM. An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism. Nat Commun. 2021;12:1623.
Nielsen SR, Strøbech JE, Horton ER, Jackstadt R, Laitala A, Bravo MC, Maltese G, Jensen ARD, Reuten R, Rafaeva M, Karim SA, Hwang CI, Arnes L, Tuveson DA, Sansom OJ, Morton JP, Erler JT. Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade. Nat Commun. 2021;12(1):3414.
Race AM, Sutton D, Hamm G, Maglennon G, Morton JP, Strittmatter N, Campbell A, Sansom OJ, Wang Y, Barry ST, Takáts Z, Goodwin RJA, Bunch J. Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration. Anal Chem. 2021;93(6):3061-3071.
Sharbeen G, McCarroll JA, Akerman A, Kopecky C, Youkhana J, Kokkinos J, Holst J, Boyer C, Erkan M, Goldstein D, Timpson P, Cox TR, Pereira BA, Chitty JL, Fey SK, Najumudeen AK, Campbell AD, Sansom OJ, Ignacio RMC, Naim S, Liu J, Russia N, Lee J, Chou A, Johns A, Gill AJ, Gonzales-Aloy E, Gebski V, Guan YF, Pajic M, Turner N, Apte MV, Davis TP, Morton JP, Haghighi KS, Kasparian J, McLean BJ, Setargew YFI, Apgi A, Phillips PA. Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma determine response to SLC7A11 inhibition. Cancer Res. 2021; 81:3461–79
Heinrich MA, Mostafa A, Morton JP, Hawinkels L, Prakash J. Translating complexity and heterogeneity of pancreatic tumor: 3D in vitro to in vivo models. Adv Drug Deliv Rev. 2021;174:265-293.
Watt DM, Morton JP. Heterogeneity in Pancreatic Cancer Fibroblasts-TGFβ as a Master Regulator? Cancers (Basel). 2021; 13:4984
2020
Ahmed AA, Angell R, Oxenford S, Worthington J, Williams N, Barton N, Fowler TG, O'Flynn DE, Sunose M, McConville M, Vo T, Wilson WD, Karim SA, Morton JP, Neidle S. Asymmetrically Substituted Quadruplex-Binding Naphthalene Diimide Showing Potent Activity in Pancreatic Cancer Models. ACS Med Chem Lett. 2020;11(8):1634-1644.
Blagih J, Zani F, Chakravarty P, Hennequart M, Pilley S, Hobor S, Hock AK, Walton JB, Morton JP, Gronroos E, Mason S, Yang M, McNeish I, Swanton C, Blyth K, Vousden KH. Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses. Cell reports. 2020;30:481-496.e486.
Brunton H, Caligiuri G, Cunningham R, Upstill-Goddard R, Bailey UM, Garner IM, Nourse C, Dreyer S, Jones M, Moran-Jones K, Wright DW, Paulus-Hock V, Nixon C, Thomson G, Jamieson NB, McGregor GA, Evers L, McKay CJ, Gulati A, Brough R, Bajrami I, Pettitt SJ, Dziubinski ML, Barry ST, Grutzmann R, Brown R, Curry E, Glasgow Precision Oncology L, Australian Pancreatic Cancer Genome I, Pajic M, Musgrove EA, Petersen GM, Shanks E, Ashworth A, Crawford HC, Simeone DM, Froeling FEM, Lord CJ, Mukhopadhyay D, Pilarsky C, Grimmond SE, Morton JP, Sansom OJ, Chang DK, Bailey PJ, Biankin AV. HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer. Cell reports. 2020;31(6):107625.
Dreyer SB, Jamieson NB, Morton JP, Sansom OJ, Biankin AV, Chang DK. Pancreatic Cancer: From Genome Discovery to PRECISION-Panc. Clinical oncology (Royal College of Radiologists (Great Britain)). 2020; 32: 5-8
Michalopoulou E, Auciello FR, Bulusu V, Strachan D, Campbell AD, Tait-Mulder J, Karim SA, Morton JP, Sansom OJ, Kamphorst JJ. Macropinocytosis Renders a Subset of Pancreatic Tumor Cells Resistant to mTOR Inhibition. Cell reports. 2020; 30: 2729 - 2742.e4
Muthalagu N, Monteverde T, Raffo-Iraolagoitia X, Wiesheu R, Whyte D, Hedley A, Laing S, Kruspig B, Upstill-Goddard R, Shaw R, Neidler S, Rink C, Karim SA, Gyuraszova K, Nixon C, Clark W, Biankin AV, Carlin LM, Coffelt SB, Sansom OJ, Morton JP, Murphy DJ. Repression of the Type I Interferon pathway underlies MYC & KRAS-dependent evasion of NK & B cells in Pancreatic Ductal Adenocarcinoma. Cancer discovery. 2020;
2019
Auciello FR, Bulusu V, Oon C, Tait-Mulder J, Berry M, Bhattacharyya S, Tumanov S, Allen-Petersen BL, Link J, Kendsersky ND, Vringer E, Schug M, Novo D, Hwang RF, Evans RM, Nixon C, Dorrell C, Morton JP, Norman JC, Sears RC, Kamphorst JJ, Sherman MH. A stromal lysolipid-autotaxin signaling axis promotes pancreatic tumor progression. Cancer Discov. 2019; doi: 10.1158/2159-8290.Cd-18-1212
Bott AJ, Shen J, Tonelli C, Zhan L, Sivaram N, Jiang YP, Yu X, Bhatt V, Chiles E, Zhong H, Maimouni S, Dai W, Velasquez S, Pan JA, Muthalagu N, Morton J, Anthony TG, Feng H, Lamers WH, Murphy DJ, Guo JY, Jin J, Crawford HC, Zhang L, White E, Lin RZ, Su X, Tuveson DA, Zong WX. Glutamine Anabolism Plays a Critical Role in Pancreatic Cancer by Coupling Carbon and Nitrogen Metabolism. Cell reports. 2019;29:1287-1298.e1286
Conway JR, Herrmann D, Evans TJ, Morton JP, Timpson P. Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine. Gut. 2019; 68: 742-58.
Halbrook CJ, Pontious C, Kovalenko I, Lapienyte L, Dreyer S, Lee HJ, Thurston G, Zhang Y, Lazarus J, Sajjakulnukit P, Hong HS, Kremer DM, Nelson BS, Kemp S, Zhang L, Chang D, Biankin A, Shi J, Frankel TL, Crawford HC, Morton JP, Pasca di Magliano M, Lyssiotis CA. Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer. Cell Metab. 2019; 29:P1390-1399.e6
Hari P, Millar FR, Tarrats N, Birch J, Quintanilla A, Rink CJ, Fernandez-Duran I, Muir M, Finch AJ, Brunton VG, Passos JF, Morton JP, Boulter L, Acosta JC. The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype. Science advances. 2019;5 doi:10.1126/sciadv.aaw0254
Leach J, Morton JP, Sansom OJ. Neutrophils: Homing in on the myeloid mechanisms of metastasis. Molecular immunology. 2019;110:69-76.
Liko D, Mitchell L, Campbell KJ, Ridgway RA, Jones C, Dudek K, King A, Bryson S, Stevenson D, Blyth K, Strathdee D, Morton JP, Bird TG, Knight JRP, Willis AE, Sansom OJ. Brf1 loss and not overexpression disrupts tissues homeostasis in the intestine, liver and pancreas. Cell Death Differ. 2019; 26: 2535–2550
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 alphavbeta6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy. The Journal of pathology. 2019; 249:332–342
Pereira BA, Vennin C, Papanicolaou M, Chambers CR, Herrmann D, Morton JP, Cox TR, Timpson P. CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer. Trends in cancer. 2019;5:724-741.
Vennin C, Melenec P, Rouet R, Nobis M, Cazet AS, Murphy KJ, Herrmann D, Reed DA, Lucas MC, Warren SC, Elgundi Z, Pinese M, Kalna G, Roden D, Samuel M, Zaratzian A, Grey ST, Da Silva A, Leung W, Mathivanan S, Wang Y, Braithwaite AW, Christ D, Benda A, Parkin A, Phillips PA, Whitelock JM, Gill AJ, Sansom OJ, Croucher DR, Parker BL, Pajic M, Morton JP, Cox TR, Timpson P. CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan. Nature communications. 2019;10:3637.
2018
Allen-Petersen BL, Risom T, Feng Z, Wang Z, Jenny ZP, Thoma MC, Pelz KR, Morton JP, Sansom OJ, Lopez CD, Sheppard B, Christensen DJ, Ohlmeyer M, Narla G, Sears RC. Activation of PP2A and inhibition of mTOR synergistically reduce MYC signaling and decrease tumor growth in pancreatic ductal adenocarcinoma. Cancer Res 2018; 79
Besray Unal E, Kiel C, Benisty H, Campbell A, Pickering K, Bluthgen N, Sansom OJ, Serrano L. Systems level expression correlation of Ras GTPase regulators. Cell Commun Signal 2018; 16(1): 46.
Candido JB, Morton JP, Bailey P, Campbell AD, Karim SA, Jamieson T, Lapienyte L, Gopinathan A, Clark W, McGhee EJ, Wang J, Escorcio-Correia M, Zollinger R, Roshani R, Drew L, et al. CSF1R(+) Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype. Cell Rep 2018;23(5):1448-60.
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, et al. Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer. Gut 2018; 67: 2142-55.
Conway JRW, Warren SC, Herrmann D, Murphy KJ, Cazet AS, Vennin C, Shearer RF, Killen MJ, Magenau A, Melenec P, Pinese M, Nobis M, Zaratzian A, Boulghourjian A, Da Silva AM, et al. Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer. Cell Rep 2018;23(11):3312-3326
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, et al. MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance. Nat Commun 2017; 8(1): 1728.
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(6):644.
Mackay HL, Moore D, Hall C, Birkbak NJ, Jamal-Hanjani M, Karim SA, Phatak VM, Pinon L, Morton JP, Swanton C, Le Quesne J, Muller PAJ. Genomic instability in mutant p53 cancer cells upon entotic engulfment. Nat Commun 2018;9(1):3070.
Marchetti C, Zyner KG, Ohnmacht SA, Robson M, Haider SM, Morton JP, Marsico G, Vo T, Laughlin-Toth S, Ahmed AA, Di Vita G, Pazitna I, Gunaratnam M, Besser RJ, Andrade ACG, et al. Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G-Quadruplex-Binding Small Molecule. J Med Chem 2018;61(6):2500-17.
Meiser J, Schuster A, Pietzke M, Vande Voorde J, Athineos D, Oizel K, Burgos-Barragan G, Wit N, Dhayade S, Morton JP, Dornier E, Sumpton D, Mackay GM, Blyth K, Patel KJ, et al. Increased formate overflow is a hallmark of oxidative cancer. Nat Commun 2018;9(1):1368.
Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, Charlton L, Knight J, Calka M, McGhee E, Dornier E, Sumpton D, Mason S, Echard A, Klinkert K, et al. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels. Nat Commun 2018; 9: 5069.
Schofield HK, Zeller J, Espinoza C, Halbrook CJ, Del Vecchio A, Magnuson B, Fabo T, Daylan AEC, Kovalenko I, Lee HJ, Yan W, Feng Y, Karim SA, Kremer DM, Kumar-Sinha C, et al. Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma. JCI Insight 2018;3(2).
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 2018;154: 820-838
Warren SC, Nobis M, Magenau A, Mohammed YH, Herrmann D, Moran I, Vennin C, Conway JR, Melenec P, Cox TR, Wang Y, Morton JP, Welch HC, Strathdee D, Anderson KI, et al. Removing physiological motion from intravital and clinical functional imaging data. Elife 2018;7.
Conway JR, Herrmann D, Evans TJ, Morton JP, Timpson P. Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine. Gut 2018.
2017
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
Morton JP, Sansom OJ. CXCR2 inhibition in pancreatic cancer: opportunities for immunotherapy? Immunotherapy 2017; 9: 9-12
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.
