Project description:A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases [breast cancer validation cohort]
Project description:This work evaluates new and specific therapeutic targets and molecular diagnostic markers connected to the TGF-b response system in chronic fibrotic diseases.
Project description:The functional decline of the vascular niches is linked to several disorders, including neurodegeneration and bone loss. However, the causes of this decline are poorly understood. A key signature of aging is the progressive damage of the microvasculature, but a clear picture of its determinants and therapeutic targets in a human context is lacking. We designed/validated a novel approach based on long-living human microvascular networks to study the age-dependent modulation of the endothelium by microenvironment and serum. Young fibroblasts restored the barrier function of aged endothelial cells, an effect counteracted by old serum. Among the involved factors, ANGPTL4 played a key role in restoring cell-cell junctions and vascular barrier. Once validated, we employed this strategy to identify potential targets involved in the degeneration of the Blood Brain Barrier (BBB) in Alzheimer Disease (AD) patients. Using serum from AD as well as from age-matched healthy donors, we demonstrated that PTP4A3 played a critical role in the regulation of vascular permeability and that its inhibition restored the functionality of the BBB exposed to serum from AD patients. We believe our strategy will be an invaluable tool to identify and therapeutically modulate the aging signature of the endothelium in the context of age-related diseases.
Project description:This work evaluates new and specific therapeutic targets and molecular diagnostic markers connected to the TGF-b response system in chronic fibrotic diseases. Keywords: other
Project description:We provided a comprehensive single-cell transcriptomic atlas of murine liver non-parenchymal cells (NPCs) in different diseases and analyzed the heterogeneity of inter- and intra-group NPCs. Our study offers a valuable resource for better understanding liver physiology and pathology, and bring new directions for the development of clinical diagnostic markers and effective therapeutic targets.
Project description:This study identified informative gene expression signatures in peripheral blood cells that can characterize TAA status and subtypes of TAA. Moreover, a 41-gene classifier based on expression signature can identify TAA patients with high accuracy. The transcriptional programs in peripheral blood leading to the identification of these markers also provide insights into the mechanism of development of aortic aneurysms, and highlight potential targets for therapeutic intervention. The classifier genes identified in this study and validated by TaqMan® real-time PCR assays define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA. Keywords: Gene Expression Signature
Project description:We generated HEK293 cells stably expressing diseases-derived mutants and performed a genome-wide transcriptome analysis using the 60K SurePrint G3 Human gene expression microarray technology. By the analysis of their gene expression profiles, we identified diseases-associated signature genes that may serve as diagnostic markers or therapeutic targets for the diseases.
Project description:With the development of frontier technologies in system biology, traditional omics-drove phenotypic studies are insufficient to decipher the diseases. Therefore, for a thorough understanding of the molecular mechanisms of diseases to investigate novel drug targets, traditional phenotypic studies must be broken through to the functional exploration of molecules. Meanwhile, the intuitive role of small molecule compounds (metabolites) in pathogenesis, precision diagnosis and therapy are gradually recognized compared to macromolecules such as DNA, RNA and proteins. Therefore, we pioneeringly proposed Spatial Temporal Operative Real Metabolomics (STORM) strategy that established a relationship between metabolic phenotypes and functions to accurately character abnormal metabolisms and further identify operative functional molecules as novel therapeutic targets. Here, given the difficulty of pancreatic cancer (PC) treatment and the high resistance of clinical drugs, we were committed to explore new targets and drugs of pancreatic cancer from a small molecular functional perspective via STORM strategy. Fortunately, based on targeted metabolomics, we found that gemcitabine, one of the most effective clinical anti-PC drugs, served as a dual modulator that promote the accumulation of functional metabolic molecules in purine metabolism to activate down-streamed kinases. And the quantitative consequences of related enzymes annotated the unique molecular mechanisms of purine metabolism regulations by gemcitabine. Collectively, we broadened the cognitions of gemcitabine in tumor inhibition, providing potential strategies for treating PC with small molecules modification. Even more importantly, with the integration of multiple frontier technologies, the STORM strategy has proven to be well adapted to the phenotypic era of functional molecules devoted to innovate molecule mechanism annotation and therapeutic discovery.
