BioMediTech Research Groups

Toxicology and Pharmacology

Group Leader: Associate Professor Dario Greco

About Us

GrecoLab is interested in studying the effects of various types of chemical exposure on biological systems, and their primary mechanism of action. While classical toxicology tries to associate intrinsic properties of the exposures with their biological outcomes, systems toxicology models the complex chem-bio interactions by considering also the molecular alterations happening in the exposed biological systems.

GrecoLab primarily focuses on modelling the effects of a new class of compounds, the engineered nanomaterials (ENMs), by interrogating multiple molecular districts of the exposed systems, using omics technologies. We then systematically integrate these layers of information with exposure outcomes and the intrinsic properties of the exposures. Advanced bioinformatics analysis is used to achieve two goals:

  1. infer the complex underlying molecular networks, relating intrinsic exposure properties and phenotypic effects, to define pathways of toxicity;
  2. find robust predictive integrated models that can help to predict the toxicity of the exposure.

GrecoLab also uses well established approaches in modern toxicology, namely the QSAR (quantitative structure-activity relationship) models, and the read across. In addition, chem-bio interactions are also modelled by novel approaches, where both the intrinsic signature and the biosignature of the exposures are considered. Further, the intrinsic and molecular signatures of the exposures are systematically exploited in two directions:

  • to explain mechanisms of human pathogenicity, explored in the frame of molecular epidemiology;
  • to predict novel therapeutic possibilities, in the field of precision and personalized medicine.

Systems toxicology approaches offer great promise to overcome the burden related to the very slow and laborious classical toxicology assessment and, at the same time, it opens unprecedented possibilities to design safer and more effective drugs, chemicals, and materials.

Achievements

GrecoLab has:

  • Developed the first systems toxicology based classifier to predict the effects of engineered nanomaterials based on a combination of intrinsic and mechanism of action properties.
  • Defined new hybrid approaches, based on omics data modelling and classical toxicology testing, to replace in vivo studies with in vitro assays to model the effects of engineered nanomaterials.
  • Established strategies of multi-omics data modelling to define adverse outcome pathways (AOP) of engineered nanomaterials (ENMs).
  • Developed the first biosignature-based read-across computational framework to link chemical exposures to human diseases.
  • Discovered new key epigenomic motifs as potential therapeutic targets of cancers.
  • Developed user-friendly software for omics data analysis and modelling to facilitate the integration of omics-derived evidence in chemical risk assessment.

Collaboration offer and requests

GrecoLab is immerged in a rich network of collaborations in Finland and abroad. Topics related to the focus areas of the group, such as systems toxicology, predictive pharmacology, (multi)-omics data analysis, integration and modelling, DNA microarray data generation, are positively considered for new collaborations.

Major Publications

  1. Kinaret P, et al. Network Analysis Reveals Similar Transcriptomic Responses to Intrinsic Properties of Carbon Nanomaterials in Vitro and in Vivo. ACS Nano. 2017 Apr 25;11(4):3786-3796. doi: 10.1021/acsnano.6b08650.
  2. Kinaret P, et al. Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs. ACS Nano. 2017 Jan 24;11(1):291-303. doi: 10.1021/acsnano.6b05652.
  3. Rydman EM, et al. A Single Aspiration of Rod-like Carbon Nanotubes Induces Asbestos-like Pulmonary Inflammation Mediated in Part by the IL-1 Receptor. Toxicol Sci. 2015 Sep;147(1):140-55.
  4. Palomäki J, et al. A secretomics analysis reveals major differences in the macrophage responses towards different types of carbon nanotubes. Nanotoxicology. 2014 Oct 17:1-10.
  5. Rydman EM, et al. Inhalation of Rod-Like Carbon Nanotubes Causes Unconventional Allergic Airway Inflammation. Part Fibre Toxicol. 2014 Oct 16;11:48.
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