ILS toxicogenomic studies assess mode-of-action (MOA) by integrating state-of-the-art gene expression profiling via next-generation sequencing technology into traditional in vitro and in vivo toxicology studies.
ILS toxicogenomics studies are a powerful tool for the safety assessment of pre-clinical candidates, as well as novel small molecule and commodity chemicals. Data can be used to:
- Establish mode-of-action for target and off-target effects
- Identify early potential liabilities of pre-clinical candidates in pharmaceutical development
- Identify common response pathway(s) for development of gene signature biomarkers
- Enable early safety assessment in discovery toxicology using high-throughput targeted gene expression
- Determine quantitative bench mark dose (BMD) relationships between-dose and gene-expression based pathway responses for use in risk assessments
Our experimental designs for toxicogenomic studies employ dose-response studies — from human-relevant levels to exposure levels used in regulatory studies — with a focus on identifying NOEL and benchmark doses useful in risk assessments, and determining thresholds of toxicological concern.
With a deep background in toxicogenomics and genetic and molecular toxicology, our team conducts studies aimed at identifying cellular and genomic response pathways to xenobiotic exposures. ILS studies can provide data in a timely manner to boost understanding of potential adverse effects and relevance to humans and facilitate informed decision-making.
With our fully integrated capabilities, ILS can deliver turnkey toxicology solutions that include gene expression profiling integrated into traditional studies. We will design studies for optimal downstream statistical evaluation, run in vivo or in vitro studies, process samples by next-generation sequencing, and offer bioinformatics support to determine biological relevance and significance of the data.
ILS staff have the scientific expertise to provide a comprehensive investigative toxicology approach to assess MOA by integrating genomic profiling into traditional toxicology studies and applying computational tools using a broad spectrum of in vitro and animal model test systems. ILS can assess and integrate traditional apical endpoints, histopathology and state-of-the-art novel approaches to assist clients in decision making. ILS has published many findings related to mode-of-action (MOA) in the peer reviewed literature and include OECD test guideline compliant regulatory testing, mechanistic studies on pathways of detoxication and use of genotoxic versus nongenotoxic MOA biomarkers. The ILS toxicogenomics team has worked with a broad spectrum of test articles, tissues and archival formalin fixed paraffin blocks (FFPE). The team is led by internationally recognized scientists with MOA and regulatory toxicology expertise, who currently serve on three scientific journal editorial boards.