The goal of the Cancer and Developmental Biology Research Group is to study how aberrant activation of embryonic signalling pathways contributes to the initiation, growth, and self-renewal of cancer. This work is based on the idea that a very limited number of signalling pathways, which are highly conserved in evolution, is required for self-renewal in development, organ repair, and cancer.

The primary focus of the laboratory is investigating the mechanisms underlying the development and progression of paediatric solid tumours, brain tumours and lung cancer, leading to the development of novel therapies, or repurposing of existing therapies, for maximal anti-tumorigenic effect and minimal associated patient side-effects. Using a broad range of developmental, molecular and cancer biology techniques in combination with in vivo mouse models, the laboratory is specifically interested in tumours associated with poor outcomes including malignancies of the brain (diffuse midline gliomas and atypical teratoid rhabdoid tumour), bone (osteosarcoma) and lung adenocarcinoma.

The team has played a part in understanding the significance of normal and abnormal Hedgehog signalling (Hh) and epigenetic regulation in development and cancer. The clinical focus of the laboratory is the application of Hh pathway inhibitors or pharmacological epigenetic regulators to childhood malignancies and lung cancer.

The team’s experimental work includes

• Paediatric solid tumours (including brain tumours and sarcomas)
• Non-small cell lung cancer
• Hedgehog signalling biology
• Epigenetics
• Preclinical models of cancer (including genetic, allograft and xenograft mouse models)

Collaborators
Professor Neil Watkins (CancerCare Manitoba)
Professor Alejandro Sweet-Cordero (UCSF)
A/Professor Javad Nazarian (DIPG Research Institute)
A/Professor Matt Dun (University of Newcastle)
Professor David Ashley (Duke)
Dr Pouya Faridi (Monash University)

For information on available projects and positions within the Development and Cancer Biology Research group please contact Dr Jason Cain.

Research Group

• Dr Nataliya Zhukova, VPCC PhD Student, Research Scientist
• Dr Vijesh Vaghjiani, Postdoctoral Scientist
• Dr Lakshmi (Priya) Sundaravel, Research Assistant - Volunteer, Research Support Staff
• Shaye Game, PhD Student
• Sukhpreet Singh, PhD Student
• Christie Sun, PhD Student
• Dr Nataliya Zhukova, VPCC PhD Student, PhD Student
• Yee Farn Goh, Masters Student

Selected publications

• Cochrane CR, Vaghjiani V, Szczepny A, Jayasekara WSN, Gonzalez-Rajal A, Kikuchi K, McCaughan GW, Burgess A, Gough DJ, Watkins DN, Cain JE (2020) Trp53 and Rb1 Regulate Autophagy and Ligand-Dependent Hedgehog Signaling. J Clin Invest 130:4006-4018.

• Cain JE, Watkins DN (2020) p53 and RB1 regulate Hedgehog responsiveness via autophagy-mediated ciliogenesis. Mol Cell Oncol 7:1805095.

• Chong WC, Cain JE (2020) Lessons learned from the developmental origins of childhood renal cancer. Anat Rec (Hoboken), 303:2561-2577.

• Zhou T, Khan S, Downie P, Cain JE (2019) Diffuse intrinsic pontine gliomas: translation of genomic knowledge to clinical practice. OBM Neurobiology, doi:21926/obm.neurobiol.1901022

• Marini KD, Croucher DR, McCloy RA, Gonzalez-Rajal A, Hastings JF, Jayasekara WSN, Alamgeer M, Boolell V, Vaghjiani V, Szczepny A, Han JZR, Waugh T, Lee HC, Oakes SR, Kumar B, Harrison CA, Lorensuhewa N, Kita B, Barrow R, Robinson BW, deKretser DM, Wu J, Ganju V, Burgess A, Martelotto LG, Rosello FJ, Cain JE*, Watkins DN* (2018) Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy. Sci Trans Med 10:eaat3504. *Co-corresponding authors.

• Szczepny A, Carey K, McKenzie L, Jayasekara WSN, Rosello F, Gonzalez-Rajal A, McCaw AS, Popovski D, Wang D, Sadler AJ, Mahar A, Russel PA, Wright G, McCloy RA, Garama DJ, Gough DJ, Baylin SB, Burgess A, Cain JE*, Watkins DN* (2018) The tumor suppressor Hic1 maintains chromosomal stability independent of Tp53. Oncogene 37:1939-1948. *Co-corresponding authors

• Muscat A, Popovski D, Jayasekara WSN, Rossello FJ, Alamgeer M, Algar EM, Ferguson M, Watkins DN, Cain JE, Ashley DM (2016) Low-Dose Histone Deacetylase Inhibitor Treatment Leads to Tumour Growth Arrest and Multi-lineage Differentiation of Malignant Rhabdoid Tumours. Clin Cancer Res 22:3560-3570.

• Ramaswamy V, Hielscher T, Mack SC, Lassaletta A, Lin T, Pajtler K, Jones DTW, Luu B, Cavalli FMG, Aldape K, Remke M, Mynarek M, Rutkowski S, Gururangan S, McLendon RE, Lipp ES, Dunham C, Hukin J, Eisenstat DD, Fulton D, van Landeghem FK, Santi M, van Veelen ML, Van Meir EG, Osuka S, Fan X, Muraszko KM, Tirapelli DPC, Oba-Shinjo SM, Marie SK, Carlotti CG, Lee JY, Rao AA, Giannini C, Faria CC, Nunes S, Mora J, Hamilton RL, Hauser P, Jabado N, Petrecca K, Jung S, Massimi L, Zollo M, Cinalli G, Bognár L, Klekner A, Hortobágyi T, Leary S, Ermoian RP, Olson JM, Leonard JR, Gardner C, Grajkowska WA, Chambless LB, Cain J, Eberhart CG, Ahsan S, Massimino M, Giangaspero F, Buttarelli FR, Packer RJ, Emery L, Yong WH, Soto H, Liau LM, Everson R, Grossbach A, Shalaby T, Grotzer M, Karajannis MA, Zagzag D, Wheeler H, von Hoff K, Alonso MM, Tuñon T, Schüller U, Zitterbart K, Sterba J, Chan JA, Guzman M, Elbabaa SK, Colman H, Dhall G, Fisher P, Fouladi M, Gajjar A, Goldman S, Hwang E, Kool M, Ladha H, Vera-Bolanos E, Wani K, Lieberman F, Mikkelsen T, Omuro AM, Pollack IF, Prados M, Robins HI, Soffietti R, Wu J, Metellus P, Tabori U, Bartels U, Bouffet E, Hawkins CE, Rutka JT, Dirks P, Pfister SM, Merchant T, Gilbert MR, Armstrong TS, Korshunov A, Ellison DW, Taylor MD (2016) Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. J Clin Oncol 34:2468-2477.

• Cochrane CR, Szczepny A, Watkins DN, Cain JE (2015) Hedgehog Signaling in the Maintenance of Cancer Stem Cells. Cancers 7:1554-1585.

• Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, Morrison A, Lewis P, Bouffet E, Bartels U, Zuccaro J, Agnihotri S, Ryall S, Barszczyk M, Chornenkyy Y, Bourgey M, Bourque G, Montpetit A, Cordero F, Castelo-Branco P, Mangerel J, Tabori U, Ho KC, Huang A, Taylor KR, Mackay A, Bendel AE, Nazarian J, Fangusaro JR, Karajannis MA, Zagzag D, Foreman NK, Donson A, Hegert JV, Smith A, Chan J, Lafay-Cousin L, Dunn S, Hukin J, Dunham C, Scheinemann K, Michaud J, Zelcer S, Ramsay D, Cain J, Brennan C, Souweidane MM, Jones C, Allis CD, Brudno M, Becher O, Hawkins C (2014) Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet 46:451-456.

• Cain JE, McCaw A, Jayasekara S, Rossello FJ, Marini KD, Irving AT, Kansara M, Thomas DM, Ashley DM, Watkins DN (2013) Sustained Treatment With Low Dose Histone Deacetylase Inhibitor LBH589 Induces Terminal Differentiation of Osteosarcoma Cells. Sarcoma 2013:608964.

• Kelleher FC, Cain JE, Healy JM, Watkins DN, Thomas DM (2012) Prevailing importance of the hedgehog signaling pathway and the potential for treatment advancement in sarcoma.  Pharmacol Ther 136:153-168.

• Cain JE, Islam E, Haxho F, Blake J, Rosenblum ND (2011) GLI3 repressor controls functional development of the mouse ureter.  J Clin Invest 121:1199-1206.