In vitro studies to characterize the impact of legacy and replacement PFAS and of human-relevant PFAS mixtures on cholesterol homeostasis in human liver cells
ESR //06
Early Stage Researcher: Faezeh Sadrabadi Haghighi
Host: German Federal Institute for Risk Assessment (BfR)
Supervisor: Albert Braeuning (BfR)
Co-supervisor: Pim Leonards (VU), Thorsten Buhrke (BfR)
Duration: 36 months
Scientific deliverables: 2.2, 2.3, 2.4, 2.9
Main WP: 2
Co-WPs: 1, 4
Enrolment in Doctoral degree: Technische Universität Berlin
Objectives
1) Impact of PFOA, PFOS, replacement PFAS, and human-relevant PFAS mixtures on cholesterol homeostasis by using human hepatocyte cell models. 2) A broad set of in vitro bioassays will be employed to identify effects of PFAS on cholesterol synthesis and metabolism including relevant molecular and cellular endpoints such as nuclear receptor activation, gene expression analysis, activity of relevant cholesterol and bile acid transporters, and determination of cholesterol and relevant metabolites. 3) Link the in vitro data to results of ESR9 regarding gene expression and metabolomic profiles altered by PFAS in human blood samples.
Planned secondment(s):
VU (M13, 4w) to get trained in metabolomic techniques.
KI (M31, 4w) to integrate in vitro toxicity profiles into AOPs.
1-day visits to a local wastewater treatment facility: Svenskt Vatten (M12 after ATC3) and UFZ (after ATC6 in M24).
