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Postdoctoral Researcher

Functieomschrijving

Postdoctoral researcher

Vacancy number: 2019/0827 Apply to: November 6 2019 Education: University Employment: Temporary position Full-time/Part-time percentage: 100%

As a postdoc you will participate in dissecting the molecular mechanisms of FXR isoform expression and transcriptional regulation and investigate how these can be targeted for NASH treatment. The salary for this position is dependent on experience and background (salary scale 10). This job is based on a temporary position for 2 years.

Department

We offer a temporary position for a postdoctoral researcher for a period of 2 years. You will be employed at the Center for Molecular Medicine of the University Medical Center Utrecht. Our research program focuses to better understand the underlying cause of human metabolic diseases and associated cancer development, and to spur and contribute to the development of improved diagnostics as well as improved therapeutic approaches. In this project, we will focus on the transcriptional basis of metabolic dysregulations, in particular in non-alcoholic steatohepatitis (NASH), a liver disease associated with the obesity and type 2 diabetes pandemic. Current estimates of NASH in the global population range between 1.5% and 6.45%, with an alarming forecasted increase in the number of patients with cirrhosis and hepatocellular carcinoma. Therefore, there is a great unmet medical need to develop drugs for NASH. We seek to identify the core transcriptional mechanisms underlying the NASH, validating physiological significance, and to identify novel therapeutic interventions. In this project, we focus on the transcriptional functions of the Farnesoid X Receptor, a ligand-activated transcription factor that is activated by endogenous bile acids. We apply multiple traditional wet lab techniques and global profiling approaches in vitro and in vivo.

Profile

The candidate will be appointed in the UMC Utrecht Center for Molecular Medicine (http://cmm.umcutrecht.nl/). A major focus of the CMM is understanding the molecular mechanisms of cancer. The candidate will be embedded in the research group of Prof. Saskia van Mil at the Center for Molecular Medicine. In the van Mil group, the mechanisms by which disrupted metabolism drives cancer initiation are investigated, in order to prevent tumor initiation. Dysregulation of the interactions between diet, microbiome and host metabolism lead to non-alcoholic steatohepatitis (NASH), associated with increased risks for developing hepatocellular carcinoma. Knowledge on the molecular drivers of tumor initiation in these diseases will dictate novel cancer prevention strategies. We make use of state-of-the art proteomics, sequencing and metabolomics equipment for understanding the molecular basis of metabolism (dys)function, using liver organoids, cell lines and in vivo models. The van Mil group has a strong background in liver and intestinal physiology and extensive expertise in the analysis of transcriptional and metabolic functions of the ligand-activated transcription factor FXR. The Farnesoid X Receptor (FXR) is a promising therapeutic target for NASH because it regulates fat, sugar and amino acid homeostasis, and protects against HCC development. Indeed, the first clinical trials suggest that FXR agonists significantly ameliorate NASH severity, however, only a minority of patients experienced a complete cure, and the treatment itself induced pruritus and dyslipidemia. Our recent data on FXR isoform functions give new insights to potentially improve treatment efficacy.

The maximum salary for this position (100%) is € 4.481,00 gross per month based on full-time employment (work week 36 hours). This job is based on a temporary position for 2 years.

In addition, we offer an annual benefit of 8.3%, holiday allowance, travel expenses and career opportunities. The terms of employment are in accordance with the Cao University Medical Centers (UMC).

For more information feel free to contact Prof Saskia van Mil (; ). Please send applications including your CV with a letter of motivation, a list of publications, and contact details of at least two references.

If you have any questions about this vacancy, please contact , , phone number: , e‑mail adress: .

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