ABSTRACT: To investigate differential protein and phospho-protein changes in the signaling cascades related to mutant G2019S LRRK2 using peripheral blood mononuclear cells (PBMCs)
Project description:Genome-Scale draft model for Human Peripheral Blood Mononuclear Cells (PBMCs). A GEM for PBMCs was developed by applying the INIT
algorithm on Human Metabolic Reconstruction (HMR 2.0) as a template model. GEMs were contextualised/ constrained for different conditions using expression datasets. The gene/transcript expression data obtained from PBMCs of Type 1 Diabetes progressors, non-progressors, and healthy controls were employed to score each reaction of HMR 2.0. For further detail please refer to Electronic Supplementary Information of Sen et.al, Metabolic alterations in immune cells associate with progression to type 1 diabetes, Diabetologia, 15/01/2020, (https://doi.org/10.1007/s00125-020-05107-6).
Project description:Differential gene expression profiling in peripheral blood mononuclear cells (PBMCs) was performed using Human Transcriptome Array 2 (HTA2)
Project description:We performed a systematic analysis of differential gene expression in a wide set of peripheral human immune cells of MPO-deficient patients using single cell RNA-sequencing (scRNAseq) of peripheral blood mononuclear cells (PBMCs) in stable disease state.
Project description:Supported by the Michael J Fox Foundation we established a biorepository of blood cells from G2019S LRRK2-PD patients recruited at the Hospital Clínic de Barcelona (Barcelona). Using this cohort, we performed a phospho-proteomic pilot study by mass spectrometry and identified a differential combination of phosphorylated proteins associated with the G2019S mutation. Here, we aim to validate and expand these findings using additional G2019S and R1441G cohorts (PMID: 35049090 By state-of-the-art DIA phospho-proteomics we aim to validate and expand our preliminary findings in additional G2019S and R1441G LRRK2 cohorts of similar design, size, and blood cell collection methods collected at additional centers in Spain (Hospital de Valdecilla in Santander, Hospital de Donostia in San Sebastian). We expect to identify differential protein phosphorylation changes in LRRK2-PD patients affected by the G2019S and R1441G mutations that could be useful as LRRK2 pharmacodynamic biomarkers. In asymptomatic LRRK2 mutation carriers, we will explore the presence of these phosphorylation changes and evaluate their applicability as early disease biomarkers.
Project description:Supported by the Michael J Fox Foundation we established a biorepository of blood cells from G2019S LRRK2-PD patients recruited at the Hospital Clínic de Barcelona (Barcelona). Using this cohort, we performed a phospho-proteomic pilot study by mass spectrometry and identified a differential combination of phosphorylated proteins associated with the G2019S mutation. Here, we aim to validate and expand these findings using additional G2019S and R1441G cohorts (PMID: 35049090 By state-of-the-art DIA phospho-proteomics we aim to validate and expand our preliminary findings in additional G2019S and R1441G LRRK2 cohorts of similar design, size, and blood cell collection methods collected at additional centers in Spain (Hospital de Valdecilla in Santander, Hospital de Donostia in San Sebastian). We expect to identify differential protein phosphorylation changes in LRRK2-PD patients affected by the G2019S and R1441G mutations that could be useful as LRRK2 pharmacodynamic biomarkers. In asymptomatic LRRK2 mutation carriers, we will explore the presence of these phosphorylation changes and evaluate their applicability as early disease biomarkers.
Project description:The SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial demonstrated clinical benefit of autologous hematopoietic stem cell transplant (HSCT) compared to cyclophosphamide (CYC) in scleroderma. We analyzed gene expression from peripheral blood mononuclear cells (PBMCs) of SCOT participants to identify those with differential treatment response.
Project description:To investigate the differential expression profile of genes and microRNA (miRNA) in peripheral blood mononuclear cells (PBMCs) from patients infected with Human T-lymphotropic Virus 1 (HTLV-1), as well as their impact on progression to Tropical Spastic Paraparesis /HTLV Associated Myelopathy (PET/HAM)