Project description:The study analyses the effect of multiple drugs on transcriptomic profile of Drosophila melanogaster. At the end of treatment, the head tissues were collected and homogenized in trizol for RNA extraction. The transcriptomic profiling was done using Affymetrix Drosophila Genome 2.0 array.
Project description:IPF is a pathological condition resulting from injury to the lungs and an ensuing fibrotic response leading to thickening of the alveolar walls and the obliteration of the alveolar space. The etiology of IPF and the role of the microenvironment in disease progression are largely unknown. We first used the repurposing pipeline to explore disease biology for the identification of relevant cell populations and then applied the screening pipeline to discover novel compounds. Using various types of RNAseq data from multiple datasets, we constructed signatures that capture different aspects of IPF biology, such as those related to cell type-specific transcriptional changes and those associated with disease development in animal models. We predicted and tested drugs targeting various IPF signatures and identified Pyrithyldione as our top candidate for reduction of fibrosis in the human precision-cut lung slices PCLS model and RNAseq was conducted on treated and untreated paired adjacent patient samples to determine its the effects on gene expression.
Project description:Clinical trials of novel therapeutics for Alzheimer's Disease (AD) have consumed a large amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA) for another indication is a more rapid and less expensive option. In this study, we profile 80 FDA-approved and clinically tested drugs in neural cell cultures, with the goal of producing a ranked list of possible repurposing candidates.
Project description:we present a novel path to drug repurposing to identify new immunotherapies for ASCVD. The integration of time of-flight mass cytometry (CyTOF) and RNA-sequencing identified unique inflammatory signatures in peripheral blood mononuclear cells (PBMCs) stimulated with ASCVD plasma. By comparing these inflammatory signatures to large-scale gene expression data from the LINCS L1000 dataset, we identified drugs that could reverse this inflammatory response. In conclusion, a systems immunology-driven drug repurposing with pre- clinical validation strategy can aid the development of new cardiovascular immunotherapies.
Project description:we present a novel path to drug repurposing to identify new immunotherapies for ASCVD. The integration of time of-flight mass cytometry (CyTOF) and RNA-sequencing identified unique inflammatory signatures in peripheral blood mononuclear cells (PBMCs) stimulated with ASCVD plasma. By comparing these inflammatory signatures to large-scale gene expression data from the LINCS L1000 dataset, we identified drugs that could reverse this inflammatory response. In conclusion, a systems immunology-driven drug repurposing with pre- clinical validation strategy can aid the development of new cardiovascular immunotherapies.
Project description:we present a novel path to drug repurposing to identify new immunotherapies for ASCVD. The integration of time of-flight mass cytometry (CyTOF) and RNA-sequencing identified unique inflammatory signatures in peripheral blood mononuclear cells (PBMCs) stimulated with ASCVD plasma. By comparing these inflammatory signatures to large-scale gene expression data from the LINCS L1000 dataset, we identified drugs that could reverse this inflammatory response. In conclusion, a systems immunology-driven drug repurposing with pre- clinical validation strategy can aid the development of new cardiovascular immunotherapies.
Project description:The discovery of effective senolytics offers a promising approach for treating many age-related diseases. In this study, we employed a phenotypic drug discovery approach, combining drug screening and drug design, to identify and develop novel senolytic agents based on the flavonoid fisetin. We successfully developed two novel flavonoid analogs, SR29384 and SR31133, which demonstrated significantly enhanced senolytic activities compared to fisetin. These analogs showed broad-spectrum efficacy in eliminating various senescent cell types, reducing tissue senescence, extending healthspan in mice, and prolonging lifespan in Drosophila. Through RNA sequencing, machine learning, and computational screening, our mechanistic studies suggest that these novel flavonoid senolytics may target PARP1, BCL2L1, and CDK2 to induce senescent cell death.