The implementation of effective treatment modalities relies on the ability to identify the appropriate and physiologically-relevant disease targets and pathways. This will greatly facilitate the translation of research discoveries into the clinical setting, as well as produce a trove of important targets for drug development and disease control.
Our research foci and infrastructure are designed to understand the genomic basis of human diseases and identify intervention points. We work in close collaboration with our clinical partners and the genome medicine group to analyse human disease samples with an emphasis on the local population. We are developing and improving genetic models of human disease ranging from stem cells and organoids to mouse models for functional genomic screens. Through functional genomics approaches, we can unravel the mechanisms behind disease initiation and progression and work towards pinpointing therapeutic targets for disease intervention and prevention in the true sense of regenerative medicine. Our models are being developed further to serve as technological platforms, enabling industry partners to do high-throughput analyses and screening.
ADVANCED “ORGANOID” MODELLING FOR NEUROGENERATIVE DISEASE AND METABOLIC SYNDROME
In the region, neurodegenerative diseases and metabolic syndrome, including Parkinson’s disease and fatty liver disease, are diseases with an increasing socio-economic impact in light of an ageing population and the increasing incidence of diabetes in Asia. Here at GIS, we are equipped with state-of-the-art technologies and research groups covering these disease entities.
For example, our researchers at GIS have developed highly complex brain organoids from stem cells that can be grown in petri dishes; they closely recapitulate the disease biology which we observe in Parkinson’s disease patients. Working together with the genomics and genome analytics groups, these models have enabled us to identify new disease targets as well as implement potential interventions that can help delay or reverse the disease state.
From donated patient tissues, we have also developed advanced liver organoids that faithfully mirror fatty liver disease in patients. This has enabled researchers at GIS to deeply understand how fatty liver disease arises in the Asian populations, how it can be prevented, and the type of treatment approaches clinicians can implement to control the progression of the disease.
DEVELOPING GENETIC TOOLS FOR MODELLING HUMAN DISEASES
Apart from this, we have also built sophisticated genetic tools to very precisely model the diseases that are relevant to the local and Asian populations. We have developed genetic mouse models bearing gene mutations for the various liver diseases. This has enabled us to understand how liver diseases originate and how one can intervene.
We further take advantage of recent advances in genetic editing and genome engineering technologies. Using CRISPR gene editing approaches, we are able to precisely introduce mutations into the stem cells and organoids we develop. This allows us to model disease in a petri dish. Combining these with screening platforms, we are equipped to identify new pathways implicated in the diseases, as well as discover new drugs that may be useful for patients.