The impact of AP – 1 on ALK dependent tumorigenesis in vivo

University of Veterinary Medicine, Vienna

Prof. Lukas Kenner

Supervisor

Publication Link

AP-1 in Lymphoma formation

Research Interest

Lukas Kenner is board certified pathologist and an internationally acknowledged expert in comparative pathology. His research interest is the exploration of molecular mechanisms in neoplastic disease, their functional relevance for tumor progression and potential for clinical i8mprovements through diagnostic and prognostic measures. He has generated several transgenic mouse models for investigating the roles of AP-1 and PDGFRB in NPM-ALK transgenic mice.

Ines Garces de los Fayos Alonso

Research student

 

Research Interest

I have always been fascinated by cell biology and the complexity of cancer. During my undergraduate at Durham University, I studied various facets of Biomedicine, ranging from Biochemistry to Haematology. These theoretical courses, alongside laboratory placements, confirmed my passion for oncological research and provided me with the foundations for my Cancer Biology Research Masters. Altogether, my experiences were critical in understanding the importance of a healthy collaborative environment in order to fuel innovative and creative research.
I hope to be able to draw on my linguistic skills, gained from living in Jordan, Lithuania, Belgium and the United Kingdom, to help me research in an inter-disciplinary and multinational manner, two founding factors promoted by the ALKATRAS programme. Under Prof. Kenner’s supervision, I will investigate the impact of AP-1 proteins on ALK–dependent tumorigenesis in vivo. I am eager to examine the communication between the tumour and its microenvironment, which has exciting “bench-to-bedside” impact potential. Therefore, as Marie Sklodowska-Curie once stated “Now is the time to understand more, so that we may fear less”.
Research description

The AP-1 transcription factors cJun and JunB are downstream effectors of ALK signalling and can directly target PDGRFB. We propose that the ALK/AP-1/PDGFRB signalling axis plays an essential part in interactions between tumours, inflammatory and stromal cells in ALK+ tumours.

Using transgenic NPM-ALK lymphoma and EML4-ALK NSCLC mouse models with conditionally deleted PDGFRB in stromal cells, in vitro 3D co-culture and primary patient samples we aim to: Investigate the crosstalk between the tumour and microenvironment of ALK+ tumours; identify transcriptional targets regulated by the tumour-stroma interaction; validate the functional contribution of selected gene products; assess the clinical relevance of selected targets

Expected Results:
To elucidate the biological function of PDGFRB for the tumour-stroma crosstalk in ALK+ tumours; to develop novel biomarkers for tumour dissemination; to refine therapy regimes for ALK+ tumours including PDGFRB inhibitors

Planned secondment(s):
Year 2: Roche (PO#3) – high throughput screen for inhibitors of selected clinical targets – 2 months; Charite, Berlin (B#8) – analysis of tumours for tumour-stroma interactions – 2 months

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