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: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.
Project description:We combined a mechanism-based and a cell-based drug screening coupled to a computational analysis, which allowed to identify potential drugs and metabolic pathways relevant for the pathophysiology of nephropathic cystinosis. This result was achieved by comparing gene-expression signature of lead compounds that share common mechanisms of action or that involve similar pathways with the disease gene-expression signature revealed by RNA-seq.
Project description:Drug repurposing is an attractive strategy for therapy development, particularly in rare diseases where traditional drug development approaches may be challenging due to high cost and small numbers of patients. Here we used a novel drug identification and repurposing pipeline to identify candidate targetable drivers of disease and corresponding therapies through application of causal reasoning using a combination of open-access resources and transcriptomics data. We optimized our approach on psoriasis as a disease model, demonstrating the ability to identify known and novel molecular drivers of psoriasis and link them to current and emerging therapies. Application of our approach to a cohort of tissue samples of necrobiosis lipoidica, an unrelated, rare, and to date molecularly poorly characterized cutaneous inflammatory disorder, identified a unique set of upstream regulators, particularly highlighting the role of IFNG and the JAK-STAT pathway as a likely driver of disease pathogenesis and linked it to JAK inhibitors as potential therapy. Analysis of an independent cohort of NL samples validated these findings with the overall agreement of drug matched upstream regulators above 96%. These data highlight utility of our approach in rare diseases and offer a novel opportunity for drug discovery in other rare diseases in dermatology and beyond.