P1 – CASA – Chemicals Altering Steroid Homone Action
We are daily exposed to hundreds of xenobiotics (environmental pollutants, industrial and occupationally relevant chemicals, body care products, food additives, supplements, recreational drugs, pharmaceuticals) that may contribute to the development and progression of diseases. Steroids essentially regulate endocrine, metabolic and immune functions, and their impaired actions are contributing to several major diseases. Thus, it is crucial to identify hazardous substances that can disrupt steroid hormone action and understand the underlying mechanisms.
This project focusses on generating experimental data that can serve as a basis to start filling existing knowledge gaps and to help establishing regulatory test systems for the characterization of EDCs. The currently available regulatory tests for EDCs mainly focus on effects on estrogen, androgen, and thyroid receptor signaling, and on sex steroid production. Therefore, we aim to address a knowledge gap and investigate whether such chemicals interfere with glucocorticoid and mineralocorticoid hormone action, in the context of immune and cardio-metabolic diseases, or whether they alter adrenal and/or gonadal steroidogenesis and might contribute to steroid modulated diseases. These represent so far neglected areas of research on endocrine active substances. For this purpose, we aim to develop and apply computational methods (WP1, led by Martin Smiesko, Uni Basel), enzyme- and cell-based models (WP2, led by Alex Odermatt, Uni Basel), steroid biosynthesis models (WP3, led by Jamal Bouitbir, Uni Basel), animal models (WP4, led by Claudia Cavelti-Weder, Uni Hospital Zürich), and analytical methods (led by Serge Rudaz, Isabel Meister and Julien Boccard). Furthermore, we aim to test certain steroid ratios as potential biomarkers for whether they can provide information on altered activities of specific enzymes and/or receptors by analyzing samples from exposed animals and/or humans. In our project, we will focus on chemicals that are also of interest for the regulators such as phthalates and bisphenol-A and their derivatives and substitutes, parabens, UV-filters, per- and polyfluorinated alkylates substances (PFAS), food additives and food contact materials, and other chemicals contained in body care and household products, and pesticides and fungicides.
Project Lead: Alex Odermatt – Universität Basel