POST-DOCTORAL POSITION IN PARIS, FRANCE

Role of the integrated stress response in alcoholic liver disease

A post-doctoral position is available at the Inserm Unit 747, in the center of Paris . Research in our group is focused on the identification of the adaptative response developed by hepatocytes upon ethanol exposure, and particularly the role played by CYP2E1 in this process. The « Integrated Stress Response », ISR, is a response pathway shared by various stress signals such as endoplasmic reticulum stress (ER stress), viral infection, amino-acid and heme deprivation.

We recently showed that ethanol and CYP2E1 induce the integrated stress response in human hepatoblastoma HepG2 cells and in a primary culture of human hepatocytes (manuscript in preparation). Indeed, synthesis of CYP2E1 (using a recombinant adenovirus expressing human CYP2E1) in HepG2 cells in combination with ethanol treatment increase both the pro-survival and the pro-apopotic programs of ISR. This study showed for the first time that CYP2E1 and ethanol lead to the activation of the integrated stress response and identified two unknown pro-apoptotic targets of ethanol and CYP2E1 : activating transcription factor 3 (ATF3) and growth arrest and DNA damage 34 (GADD34). These pathways may play an important role in hepatocyte cell death observed during alcoholic liver disease. Our project is to study :

- the molecular mechanisms involved in the induction of the integrated stress pathway by CYP2E1 and ethanol.

- the apoptosis pathways induced by ATF3 and GADD34 upon CYP2E1 and ethanol treatment.

- the expression of the ISR genes in liver biopsies samples and the correlation with CYP2E1 levels and the degree of the liver alcoholic pathology.

The position is open for up to three years; monthly gross salary is about 3200€.

Candidates should have a PhD degree. Applications, including a CV, a list of publications, and the names and e-mails of two referees, should be sent by mail or e-mail to:

Peggy Murray
Senior Advisor
Office of the Director
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
5635 Fishers Lane Room 2013
Rockville, MD 20852-7003
301-443-2594
pmurray@mail.nih.gov

Prepared:  December 11, 2007