Developmental and Cancer Biology

Developmental and Cancer Biology Research Group

Research Group Head

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 and 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 intrinsic pontine glioma, medulloblastoma, atypical teratoid rhabdoid tumour), bone (osteosarcoma) and non-small cell lung cancer.

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 sarcoma’s)
  • Non-small cell lung cancer
  • Hedgehog signalling biology
  • Epigenetics
  • Preclinical models of cancer (including genetic, allograft and xenograft mouse models)

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

Research Group

Selected publications

  • Zhou T, Khan S, Firestein R, Downie P, Cain JE (2019) Diffuse Intrinsic Pontine Glioma: Translation of Genomic Knowledge to Clinical Practice. OBM Neurobiology 3:8.

  • Saad MI, Alhayyani S, McLeod L, Yu L, Alanazi M, Deswaerte V, Tang K, Jarde T, Smith JA, Prodanovic Z, Tate MD, Balic JJ, Watkins DN, Cain JE, Bozinovski S, Algar E, Kohmoto T, Ebi H, Ferlin W, Garbers C, Ruwanpura S, Sagi I, Rose-John S, Jenkins BJ (2019) ADAM17 selectively activates the IL-6 trans-signaling/ERK MAPK axis in KRAS-addicted lung cancer. EMBO Mol Med Apr;11(4). pii: e9976.

  • Leong TL, Gayevskiy V, Steinfort DP, De Massy MR, Gonzales-Rajal A, Marini KD, Stone E, Chin V, Havryk A, Plit M, Irving LB, Jennings BR, McCloy RA, Jayasekara WSN, Alamgeer M, Boolell V, Field A, Russell PA, Kumar B, Gough DJ, Szczepny A, Ganju V, Rossello FJ, Cain JE, Papenfuss AE, Asselin-Labat ML, Cowley MJ, Watkins DN (2019) Deep multi-region whole-genome sequencing reveals heterogeneity and gene-by-environment interactions in treatment-naive, metastatic lung cancer. Oncogene 38:1661-1675. Epub 2018 Oct 22.

  • Sun X, Vaghjiani V, Jayasekara WSN, Cain JE, St John JC (2018) The degree of mitochondrial DNA methylation in tumor models of glioblastoma and osteosarcoma.  Clin Epigenetics 10:157.

  • Lim CH, Sun Q, Ratti K, Lee SH, Zheng Y, Takeo M, Lee W, Rabbani P, Plikus MV, Cain JE, Wang DH, Watkins DN, Millar S, Taketo MM, Myung P, Cotsarelis G, Ito M (2018) Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing. Nature Communications 9:4903.

  • 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 activing signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy. Science Translational Medicine 10(451). *Co-corresponding authors. AbstractReprintFull text.

  • 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

  • Szczepny A, Rogers S, Jayasekara WSN, Park K, McCloy RA, Cochrane CR, Ganju V, Cooper WA, Sage J, Peacock CD, Cain JE, Burgess A, Watkins DN. The Role of Canonical and Non-Canonical Hedgehog Signaling in Tumor Progression in a Mouse Model of Small Cell Lung Cancer. Oncogene, 2017, 36(39):5544-5550.

  • Muscat A, Popovski D, Jayasekara WS, Rossello FJ, Ferguson M, Marini KD, Alamgeer M, Algar EM, Downie P, Watkins DN, Cain JE*, Ashley DM* (2016) Low-Dose Histone Deacetylase Inhibitor Treatment Leads to Tumor Growth Arrest and Multi-Lineage Differentiation of Malignant Rhabdoid Tumors. Clin Cancer Res 22(14):3560-3570. *co-senior and corresponding authors.

  • 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.

  • Leong TL, Marini KD, Rossello FJ, Jayasekara SN, Russell PA, Prodanovic Z, Kumar B, Ganju V, Alamgeer M, Irving LB, Steinfort DP, Peacock CD, Cain JE, Szczepny A, Watkins DN (2014) Genomic characterisation of small cell lung cancer patient-derived xenografts generated from endobronchial ultrasound-guided transbronchial needle aspiration specimens. PLoS ONE 9:e106862.

  • 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. *Corresponding author