Investigation of the nuclear functions of ALK


University of Cambridge

Dr. Suzanne Turner

Supervisor

Publication Link  ORCID Link

Paediatric lymphoma and neuroblastoma

Research Interest

Suzanne D. Turner, PhD is a Senior Lecturer in tumour biology and pathology at the University of Cambridge. She directs a research group investigating mechanisms of ALK-induced malignancies and has contributed significantly to our understanding of the carcinogenic process having created one of the first murine models of ALK-induced tumour formation. In particular, mechanisms relating to the role of the T cell receptor in ALK-induced lymphomagenesis are an interest of the Turner group.

Stephen Ducray

Research student

ORCID Link

 

Research Interest

I am a Biochemistry alumnus of Trinity College, Dublin.  I believe in undertaking purposeful research and have a specific interest in oncology, namely the dysregulation and manipulation of signalling pathways seen in cancerous cells. My project, under the supervision of Dr. Suzanne Turner in the University of Cambridge, involves the investigation of NPM-ALK (Nucleophosmin-anaplastic lymphoma kinase; a chimeric gene which encodes a constitutively activated tyrosine kinase) dependant phosphorylation of histones and their functional consequences to the cells.

Research description

NPM-ALK is located not just in the cytoplasm of ALCL cells but also in the nucleus by virtue of its ability to interact with endogenous NPM. We have shown that in the nucleus, NPM-ALK induces hosphorylation of histone H2B on tyrosine residues 37 and 40, the latter site previously reported as a target of wee1 kinase activity and the former of unknown consequence. In addition, phosphorylated NPM-ALK localizes to nuclear bodies. The functional consequences of these events to the cells in which they occur will be investigated using cell lines, murine models and validating ndings in primary patient tumours by immunohistochemistry.

Specically, we will investigate the NPM-ALK dependent phosphorylation of histones and their functional consequences to the cells; the role of NPM-ALK in the nuclear body; interacting partners of NPM-ALK in the nucleus; the clinical relevance of these ndings.

Expected Results: To elucidate the biological function of histone modications induced by NPM-ALK; to elucidate the biological function of localisation to the nuclear bodies.

Planned secondment(s):
Year 1: Medical University of Vienna – to learn techniques for the analysis of epigenetic modications and ALK analysis in tissues
Year 2: TissueGnostics – analysis of tissue arrays for the presence of nuclear events in patient samples.