Trevor Littlewood

littlewood

Oncogenic signalling in cancer.

Understanding the molecular activities of oncogenes and how they interact functionally to drive and maintain tumours is central to the identification of plausible anti-cancer therapeutic interventions. Despite the fact that the myc oncogene was discovered over thirty years ago, its nature as a pleiotropic transcription factor has complicated analysis of its precise functions. The Littlewood Group are currently investigating the mechanism of cooperation between Myc and oncogenic Ras proteins, both in cultured cells and in genetically modified animals, using reversible systemic or tissue-specific switching of oncogene expression or oncoprotein activity. Moreover, Myc exists in an interacting network of related proteins and we are trying to determine whether Myc's tumourigenic function depends on its ability to influence the activity of the proteins in this network.

Research objectives

  • What is the nature of the cooperation between Myc and Ras protein functions?

  • What are the Myc-dependent signals that instruct the tumour microenvironment?

  • How does deregulation of Myc during tumourigenesis influence the activity of the Myc network of interacting proteins?

Key publications

Bywater MJ, Burkhart DL, Straube J, Sabò A, Pendino V, Hudson JE, Quaife-Ryan GA, Porrello ER, Rae J, Parton RG, Kress TR, Amati B, Littlewood TD, Evan GI, Wilson CH (2020). Reactivation of Myc transcription in the heart unlocks its proliferative capacity. Nat. Commun., 11(1):1827. doi: 10.1038/s41467-020-15552-x

Sodir NM, Kortlever RM, Barthet VJA, Campos T, Pellegrinet L, Kupczak S, Anastasiou P, Swigart LB, Soucek L, Arends MJ, Trevor D, Littlewood TD, Evan GI (2020). Myc instructs and maintains pancreatic adenocarcinoma phenotype. Cancer Discov., 10(4):588-607. doi: 10.1158/2159-8290.CD-19-0435

Kreuzaler P, Clarke MA, Brown EJ, Wilson CH, Kortlever RM, Piterman N, Littlewood TD, Evan GI, Fisher J (2019). Heterogeneity of Myc expression in breast cancer exposes pharmacological vulnerabilities revealed through executable mechanistic modeling. Proc. Natl. Acad. Sci. U.S.A., 116(44):22399-22408. doi: 10.1073/pnas.1903485116

Kortlever RM, Sodir NM, Wilson CH, Burkhart DL, Pellegrinet L, Brown Swigart L, Littlewood TD, Evan GI (2017). Myc cooperates with Ras by programming inflammation and immune suppression. Cell, 171(6):1301-1315. doi: 10.1016/j.cell.2017.11.013

Evan GI, Hah N, Littlewood TD, Sodir NM, Campos T, Downes M, Evans RM (2017). Re-engineering the pancreas tumor microenvironment: A "regenerative program" hacked. Clin. Cancer Res., 23(7):1647-1655. doi: 10.1158/1078-0432.CCR-16-3275