Expand existing and develop new systems biology and systems pharmacology research programs to build multiscale models of disease that will lead to the identification of networks/sub-networks as drug targets and readouts of therapeutic activity and advance the validation of existing and novel targets, rational drug repositioning and rational development of combination therapy.
Launch at least 6 cross-disciplinary research programs that bring together experts in translational bioinformatics, computational biology, genetics, epidemiology, drug discovery and clinical research to develop a predictive model of the disease. Efforts should support:
- development of computational tools and infrastructure to allow basic and clinical researchers to query model in silico and validate it by using it for patient stratification, predictions of efficacy, on- and off-target adverse effects.
- identification of quantitative methods to access synergy between (1) multiple therapeutic agents and (2) pharmacologic/non-pharmacologic perturbations.
- development of phenotypic screens (in cell based and/or animal models) to advance rational drug repositioning and data-driven development of combination therapy based on the ability of individual or combinations of therapeutic agents to shift the network state away from disease.
- Research Implementation Area
- Drug Repurposing and Combination Therapy Development
- PAR-17-032: Translational Bioinformatics Approaches to Advance Drug Repositioning and Combination Therapy Development for Alzheimer’s Disease (R01)
- PAS-19-393: Small Research Grant Program for the Next Generation of Researchers in AD/ADRD Research: Area of Focus Systems Biology (Reissue of RFA-AG-19-003)
Research Programs and Resources
- Translational Bioinformatics Approaches to Advance Drug Repositioning and Combination Therapy Development for Alzheimer’s Disease