Developmental and Cancer Biology

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handsDevelopmental and Cancer Biology

Research Group Head: Dr Jason Cain

The goal of the Cancer and Developmental Biology Research Group directed by Professor Watkins 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 the Hedgehog (Hh) pathway. The team has played a part in understanding this pathway’s biological role in cancer and repair, and helped in the development of new ways of inhibiting the pathway in cancer. The clinical focus of the laboratory is small cell lung cancer (SCLC), with the goal of inhibiting the regeneration of tumours following chemotherapy.

The team’s experimental work includes:

– Mouse models of cancer
– Chemoresistance
– Epigenetics
– Stem cell biology
– Neural development
– Preclinical models of cancer

Research Group
Dr Jason Cain (Research Group Head)

Selected publications

Wang DH, Clemons NJ, Miyashita T, Dupuy, AJ, Zhang, W, Szczepny A, Corcoran-Schwartz IM, Wilburn DL, Montgomery EA, Wang JS, Jenkins NA, Copeland N, Harmon JW, Phillips WA, Watkins DN. Aberrant Epithelial-Mesenchymal Hedgehog Signalling Characterizes Barrett’s Metaplasia. Gastroenterology, 2010; 138:1810–1822.

O’Toole SA, Machalek DA, Shearer RF, Millar EKA, Nair R, Schofield P, McLeod D, Cooper CL, McNeil CM, McFarland A, Nguyen A, Ormandy CJ, Qiu MR, Rabinovich B, Martelotto LG, Vu D, Hannigan GE, Musgrove EA, Christ D, Sutherland RL, Watkins DN*, Swarbrick A* (2011) Hedgehog overexpression is associated with stromal interactions and predicts for poor outcome in breast cancer. Cancer Res 71:4002-4014. *Co-corresponding authors.

Park KS, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR, Bernard K, Conklin JF, Szczepny A, Yuan J, Guo R, Ospina B, Falzon J, Bennett S, Brown TL, Markovic A, Devereux WL, Ocasio CA, Chen JK, Stearns T, Thomas RK, Dorsch M, Buonamici S, Watkins DN, Peacock CD, Sage J  (2011) A crucial requirement for Hedgehog signaling in small cell lung cancer.  Nat Med 17:1504-1508.

Rossello F, Tothill R, Britt K, Marini K, Falzon J, Thomas D, Peacock C, Marchionni L, Li J, Bennett S, Tantoso E, Brown T, Chan P, Martelotto L, Watkins DN. Next-Generation Sequence Analysis of Cancer Xenografts. PLoS One, 2013; 8(9):e74432.

Alamgeer M, Ganju V, Szczepny A, Russell PA, Prodanovic Z, Kumar B, Wainer Z, Brown T, Schneider-Kosky M, Conron M, Wright G, Watkins DN. The prognostic significance of ALDEHYDE DEHYDROGENASE 1A1 (ALDH1A1) and CD133 expression in early-stage non-small cell lung cancer. Thorax, 2013; 68(12):1095-104.