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Toxicity Mode-of-Action Discovery (ToxMAD) Platform

DermatotoxicologyModels for Organ Specific, Developmental & Genetic ToxicityPBTK & Exposure ModellingAllergen PredictionToxicity Mode-of-Action Discovery (ToxMAD) Platform

ToxMAD is a chemical safety assessment platform based on mechanistic reasoning without relying on animal experiments. It uses novel in vitro and in silico molecular and phenotypic profiling technologies developed in A*STAR, including high-throughput image-based phenotypic profiling, proteomic profiling, transcriptomic profiling, virtual docking, 3D-structure analysis, and bioinformatics analysis.

ToxMAD can be used to rapidly and efficiently identify the modes-of-action (MoAs) of chemicals, especially key molecular initiating events and cellular events that may lead to adverse outcomes. The platform is especially useful for identifying safer replacements for chemicals of concerns, or perform rapid potency evaluations for chemicals without any safety data.


High-throughput In-vitro Phenotypic Profiling (HIPPTox) Platform

Protein allergenicity

HIPPTox is a high-throughput cellular imaging platform for performing broad bioactivity detection or cell-type-specific toxicity tests. One of the key advantages of HIPPTox over existing in vitro assays is that no assumption about toxicity mechanisms is required, and thus the platform can be used to discover new in vitro endpoints that may reflect previously unknown toxicity modes of action or mechanisms. HIPPTox has been applied to build highly-predictive assays for proximal-tubule-cell and bronchial-epithelial-cell toxicities.

Key Team Members

Dr. Lit-Hsin Loo
Ms. Jia-Ying Joey Lee
Dr. James Miller
Dr. Sreetama Basu
Dr. Su Su Htwe
Mr. Paul Cain
Ms. Jia-Wen Carmen Kong
Mr. Shufeng Oscar Fu


Computational Toxicology

Computational Toxicology

We use and develop computational methods for chemical read-across and cellular target prediction based on:

• High-throughput 2D and 3D chemical similarity including QSAR

• Binding pocket similarity searches for on- and off-target binding site prediction

• Detailed compound-target docking, including AI scoring function enhancements

• Integrative target pathway analysis

• SNP analysis for inter-individual variability

Key Team Members

Dr. Hao FAN
Dr. Minh Nguyen
Dr. Michael Sullivan
Dr. Vachiranee Limviphuvadh
Dr. Sebastian Maurer-Stroh


Protein-Protein/Chemical Interaction Profiling

Protein-Protein/Chemical Interaction Profiling

Chemicals can perturb proteins and rewire interaction networks leading to diseased phenotypes but they can also be used to alter cellular behaviours for therapeutic or industrial purposes. Our lab deploys existing and develops novel cellular biophysical techniques to study the intracellular interaction of proteins with drugs, chemicals and metabolites. We further combine these techniques with protein mass spectrometry for identifying unknown targets of drugs and chemicals in mechanism-of-action studies.

key Team members

Dr. Chris Soon Heng Tan
Mr. Hong Yun Chang


Chemogenomic Profiling

Protein-Protein/Chemical Interaction Profiling

Our platform uses chemogenomic profiling, a fitness-based assay in Saccharomyces cerevisiae, to determine targets of bioactive compounds, side-targets of drugs and delineate pathways that buffer resistance to the target pathway. Being the only platform in Asia to offer chemogenomic profiling as a service, we work with a wide spectrum of researchers across Singapore.

We have elucidated the MoA of natural compounds and synthetic drugs and boosted flavor production in yeast. We are also establishing chemogenomic profiling in mammalian cells using the Genome scale CRISPR-Cas9 Knockout (GECKO) assay which will widen the scope of our research.

key Team members

Dr. Prakash Arumugam
Dr. Alfatah Mohammad
Ms. Jin Huei Wong
Ms. Corinna Goh


 

Agency for Science, Technology and Research (A*STAR)

1 Fusionopolis Way, #20-10 Connexis North Tower, Singapore 138632

 

contact@a-star.edu.sg

 

(65) 6826 6111


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