News

29 June 2017

PD position available at Institut Pasteur de Lille, France

Post-doctoral position in hepatic metabolism, senescence and fatty liver disease (NAFLD)

Duration: 2 years

Location: Inserm UMR1011. Institut Pasteur de Lille, France

Website: http://www.u1011.lille.inserm.fr/presentation-unite/equipe/3689-2/

Contact: rejane.paumelle-lestrelin@univ-lille2.fr

Job description

A new postdoctoral position is immediately available in non-alcoholic fatty liver disease (NAFLD) research team in the laboratory of Pr. Bart Staels at Inserm UMR1011 in Lille, France. Non-alcoholic fatty liver disease (NAFLD) is a chronic liver condition which evolves, at a high rate, especially in ederly and obese patients, from simple steatosis into non-alcoholic steatohepatitis (NASH), an aggressive form of NAFLD predisposing to an increased risk of cardiovascular and progressive liver diseases, including fibrosis, cirrhosis and hepatocellular carcinoma. The natural history of age and obesity-driven NAFLD is poorly understood. However, recent studies suggested a potential role of cellular senescence in hepatocyte dysfunction, fibrosis development and adverse liver outcome. In our project, we will investigate the contribution of hepatocyte senescence to lipid metabolism and NAFLD development during aging using primary hepatocytes and distinct models of NASH development in mice. The results obtained will be validated in human by performing correlation studies between genes involved in senescence, lipid metabolism, aging and NASH using two liver cohorts of obese patients with biopsy proven NASH.

Our team received a grant from the transdisciplinary research center of longevity – contract state-region plan (CPER-CTRL) to complete this project with a 2-years post-doctoral grant

Post-doctoral profile

Postdoctoral applicant should have a PhD in cell biology, biochemistry, or a related field. Practical expertise in hepatic metabolism and NAFLD fields (preferably both) and a theoretical expertise in senescence and aging is recommended. Experiments will involve animal models of NAFLD, cell biology, transcriptomic and bio-informatic analyses. Holding a valid authorization for animal experimentation issue in an EU country is an additional asset. Motivation and ability to function autonomously is required. Applicants should send the following in a PDF: curriculum vitae, statements of research interests, a brief description of career goals, and the names and contact information of two references to rejane.paumelle-lestrelin@univ-lille2.fr.

 

 

8 November 2016

PhD student Yvonne won best poster award at EASyM

Yvonne Rozendaal, PhD student at the TU/e won the prize for the best poster at the EASyM conference in Berlin, Germany.

best-poster-award-easym

 

20 July 2016

Happy Summer!

A nice summer to all RESOLVE participants!

 

5 July 2016

PD position available

 

7 June 2016

Clara John about her research

Worldwide 1.7 billion people are affected by supernutrition and its repercussion, outpacing the global burden caused by malnutrition (Haslam and James 2005; Rosen and Spiegelman 2014). In many cases obesity (BMI > 30 kg/m2), a consequence of overnutrition, is accompanied by a disturbance of the cellular and systemic cholesterol homeostasis. According to the National Institute of Health, USA this accounts for one of the ten major risk factors for cardiovascular diseases. One of the causes leading to atherosclerosis involves impairments in vascular metabolism of cholesterol rich lipoproteins (Lewington, Whitlock et al. 2007; Ference, Yoo et al. 2012).

Due to the high metabolic activity of brown adipose tissue (BAT) and the possibility to induce the browning of different white adipose tissue-depots, the activation of BAT is considered as a therapeutic target to treat or prevent metabolic diseases. One of the main functions of BAT is the non-shivering thermogenesis (Cannon and Nedergaard 2004) leading to an increase in energy expenditure, which is paralleled by a robust stimulation of appetite and food intake including cholesterol. Whereas glucose and fatty acids serve as fuels for energy production and can be metabolized directly (Cannon and Nedergaard 2004; Bartelt, Bruns et al. 2011, an excess of cholesterol intake needs to be disposed by alternative routes to avoid the systemic accumulation of potentially cytotoxic cholesterol.

The underlying hypothesis of my work is that cold induced BAT-activation results in a dynamic adaption of vascular lipoprotein- as well as cellular sterol metabolism to maintain the general regulation of systemic cholesterol handling.

Our studies showed that the BAT-activation resulted in an increased HDL-turnover as well as reverse cholesterol transport (RCT), the movement of cholesterol from peripheral tissues back to the liver via HDL. Those results support the‘HDL-Flux-Hypothesis’proposed by Rader and Tall (2012). The hypothesis suggests that therapeutic interventions to promote HDL-mediated cholesterol efflux to the liver will reduce cardiovascular risk, regardless of whether it affects plasma cholesterol levels (Khera, Cuchel et al. 2011; Rohatgi, Khera et al. 2014). Additionally, we could observe that activated BAT induces the hepatobiliary disposal of cholesterol in form of bile acids.

These findings lead to the assumption that the activation of BAT contributes to preserve systemic cholesterol homeostasis. Future studies should therefore address the question of whether the activation of brown and beige adipocytes in humans could serve as a therapeutic target to prevent cardiovascular diseases.

 

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