Schins research group: particles, inflammation and genome integrity

Head of research group:
Dr. Roel Schins tl_files/bilder/mail.gif

Senior Researcher:

Dr. med. vet. Catrin Albrecht tl_files/bilder/mail.gif

Postdocs:

Dr. rer. nat. Tina Wahle tl_files/bilder/mail.gif

PhD student:

Adriana Sofranko, doctoral student tl_files/bilder/mail.gif
Waluree Thongkam, doctoral student tl_files/bilder/mail.gif

Master student:
Jonas Tigges tl_files/bilder/mail.gif


Technical assistance:

Gabriele Wick, TA tl_files/bilder/mail.gif

Guest Researcher:

Dr. Yolanda Irasema Chirino tl_files/bilder/mail.gif

Research profile

It is nowadays well accepted that inhalation exposure to ambient particulate matter (PM) can lead to or exacerbate various age-related diseases, including chronic obstructive pulmonary disease (COPD) and cardiovascular diseases. Long-term exposure to excessive concentrations of poorly soluble dusts are also implicated in the development of lung fibrosis and lung cancer. More recently, the gastrointestinal tract has been recognised as a potentially important uptake organ system as well target for the effects of engineered nanoparticles. A growing number of epidemiological studies also indicates that inhaled particles may be involved in the development and progression of neurodegenerative diseases like Alzheimer’s disease. In this context, the AG Schins, investigates the molecular mechanisms of toxicity of inhaled and ingested (nano)particles. The group’s previous research has substantially contributed to the identification of sustained inflammation as a key driver of the pathogenesis of particle-induced diseases including fibrosis and lung cancer. Meanwhile, this mode of action is well-established in the particle toxicology field including risk assessment, and is presently also in the centre of discussion regarding the potential genotoxicity and carcinogenicity of specific types of engineered nanomaterials. Current projects of the AG focus on the elaboration of mechanisms of direct effects of particles as well as of the effect of particle-induced inflammation on genome integrity and tissue remodelling in the respiratory tract and the central nervous system.

Projects

The project „Effects of inhaled ambient particulate matter on the mouse brain“ addresses the impact of long term inhalation exposure to ambient (ultrafine) particles on the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease in various mouse models. The project was initiated through a grant from the Research Committee of the Medical Faculty at the Heinrich Heine University and meanwhile continued upon initiation of the international Leibniz-Research Project AIRBAG (Air Pollutants and Brain Aging Research Group) by the IUF in cooperation with the Netherlands National Institute for Public Health and the Environment (RIVM) in Bilthoven.

The project “Engineered nanomaterials mechanisms of interaction with living systems and the environment (nanoMILE)” is supported by the EU Seventh Framework Programme. The project intends to establish a fundamental understanding of the mechanisms of nanomaterial interactions with living systems and the environment, across the entire life cycle of nanomaterials and in a wide range of target species. The project consortium consists of 29 partners and is coordinated by the University of Birmingham. The main role of the AG in the project involves the evaluation of neurotoxic effects of engineered nanoparticles following inhalation and oral exposure (cooperation with the working group von Mikecz).

Link nanoMILE

The project „Shape-engineered TiO2 nanoparticles for metrology of functional properties: setting design rules from material synthesis to nanostructured devices (SETNanoMetro)“ is also funded through the EU 7th framework project. The aim of the project is the development and validation of standards for the design and measurement of TiO2-based nanomaterials and nanotechnological applications. The project consortium is composed of 16 academic and industry partners and is coordinated by the Italian National Institute of Metrological Research (INRIM) in Turin. The AG addresses the nanosafety aspects in the project by using innovative in vitro toxicity testing approaches associated with inhalation and oral exposure to these nanoparticles.

Link SETNanoMetro

The project „3R-systems biology strategy for human neurotoxicity hazard risk and safety assessment (N3RvousSystem)“ has been awarded within the Dutch-German bilateral project call InnoSysTox: (Innovative systems toxicology for alternatives to animal testing), and is funded on the German part by the BMBF. The aim of this research project is the development of a strategy to detect adverse effects on the brain resulting from chemical exposure on the basis of a systems biology-based 3R-testing approach. A major goal of the project involves the evaluation of the applicability of such novel approach towards hazard and risk assessment of engineered nanomaterials. The project is carried out in cooperation with three partners in the Netherlands, i.e. Utrecht University (coordination), the RIVM in Bilthoven and PamGene in ‘s-Hertogenbosch as well as two further German partners, i.e. the IUTA in Duisburg and Tascon GmbH in Münster.

The project „MiTyrAGE“ (Nutritional targeting of the mitochondria-tyr-kinase axis to prevent age-associated neuronal decline) has been awarded within the Joint Program Initiative „A healthy diet for healthy life”(JPI HDHL), and is supported by the Federal Ministry of Education and Research (BMBF). The aim of the project is to identify and characterize nutritional interventions with possible preventive effects against age-associated cognitive decline. The project is carried out by AG Schins, AG Schikowski and the Liaison Group Ventura (project coordinator), in cooperation with the University Tor Vergata in Rome and the CSIC in Madrid. The specific role of the AG within the project is to identify and investigate nutritional factors associated with age-associated neuronal changes and to determine the underlying molecular mechanisms.

Cooperations

IUF internal:
Fritsche research group
Haendeler research group
Krutmann reserach group / team Unfried
von Mikecz research group
Schikowski research group


National:
IUTA, Institute of Energy and Environmental Technology, Duisburg

International:
RIVM, National institute for public health and the environment, The Netherlands
Maastricht University & Maastricht University Medical Centre, The Netherlands
Utrecht University, The Netherlands
Adolphe Merkle Institute, Fribourg, Switzerland
University of Turin, Italy
Paris VII University, France

Selected publications

Peeters PM, Eurlings IMJ, Perkins TN, Wouters EF, Schins RPF, Borm PJA, Drommer W, Reynaert NL, Albrecht C: Silica-Induced NLRP3 Inflammasome Activation In vitro and in Rat Lungs. Part Fibre Toxicol 11(1): 58, 2014. [pubmed] (open access)


Van Berlo D*, Hullmann M*, Wessels A, Scherbart AM, Cassee FR, Gerlofs-Nijland ME, Albrecht C, Schins RPF: Investigation of the effects of short-term inhalation of carbon nanoparticles on brains and lungs of C57BL/6J and p47phox-/- mice. Neurotoxicology 43: 65-72, 2014. (* equal contribution) [pubmed]

Gerloff K, Pereira DIA, Faria N, Boots AW, Kolling J, Förster I, Albrecht C, Powell JJ, Schins RPF: Influence of simulated gastro-intestinal conditions on particle-induced cytotoxicity and interleukin-8 regulation in differentiated and undifferentiated Caco-2 cells, Nanotoxicol  7: 353-366, 2013. [pubmed]