- Advanced Proteomics Techniques and Applications
- Chronic Kidney Disease and Diabetes
- Mass Spectrometry Techniques and Applications
- Renal Diseases and Glomerulopathies
- Advanced Glycation End Products research
- Metabolomics and Mass Spectrometry Studies
- Renal and related cancers
- Dialysis and Renal Disease Management
- Blood Pressure and Hypertension Studies
- Pediatric Urology and Nephrology Studies
- Alzheimer's disease research and treatments
- Diabetes Treatment and Management
- Protein Hydrolysis and Bioactive Peptides
- Pregnancy and preeclampsia studies
- Genetics, Aging, and Longevity in Model Organisms
- Molecular Biology Techniques and Applications
- Retinal Diseases and Treatments
- Birth, Development, and Health
- Amino Acid Enzymes and Metabolism
- Liver Diseases and Immunity
- Bladder and Urothelial Cancer Treatments
- Genetic and Kidney Cyst Diseases
- Genetic Associations and Epidemiology
- Retinal Imaging and Analysis
- Biosensors and Analytical Detection
Mosaiques Diagnostics and Therapeutics (Germany)
2015-2024
University of Toronto
2023
Hospital Universitario Fundación Jiménez Díaz
2023
Skaraborg Hospital
2023
Innsbruck Medical University
2023
Toronto General Hospital
2023
Universidad Autónoma de Madrid
2023
Umeå University
2023
Klinikum St. Georg
2023
Medizinische Hochschule Hannover
2016-2019
Because of its availability, ease collection, and correlation with physiology pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack comparable data sets from large cohorts has greatly hindered development proteomics. Here, we report establishment a reproducible, high resolution method peptidome analysis naturally occurring human urinary peptides proteins, ranging 800 to 17,000 Da, using samples 3,600 individuals analyzed by capillary electrophoresis...
Diabetic nephropathy (DN) is a progressive kidney disease, well-known complication of long-standing diabetes. DN the most frequent reason for dialysis in many Western countries. Early detection may enable development specific drugs and early initiation therapy, thereby postponing/preventing need renal replacement therapy. We evaluated urinary proteome analysis as tool prediction DN. Capillary electrophoresis-coupled mass spectrometry was used to profile low-molecular weight urine. examined...
Progressive CKD is generally detected at a late stage by sustained decline in eGFR and/or the presence of significant albuminuria. With aim early and improved risk stratification patients with CKD, we studied urinary peptides large cross-sectional multicenter cohort 1990 individuals, including 522 follow-up data, using proteome analysis. We validated that previously established multipeptide biomarker classifier performed significantly better detecting predicting progression than current...
Urinary biomarkers for diabetes, diabetic nephropathy, and nondiabetic proteinuric renal diseases were sought. For 305 individuals, defined validated in blinded data sets using high-resolution capillary electrophoresis coupled with electrospray-ionization mass spectrometry. A panel of 40 distinguished patients diabetes from healthy individuals 89% sensitivity 91% specificity. Among 102 urinary differed significantly between normoalbuminuria a model that included 65 these correctly identified...
Urinary proteomics is emerging as a powerful non-invasive tool for diagnosis and monitoring of variety human diseases. We tested whether signatures urinary polypeptides can contribute to the existing biomarkers coronary artery disease (CAD). examined total 359 urine samples from 88 patients with severe CAD 282 controls. Spot was analyzed using capillary electrophoresis on-line coupled ESI-TOF-MS enabling characterization more than 1000 per sample. In first step "training set" biomarker...
Abstract Owing to its availability, ease of collection, and correlation with pathophysiology diseases, urine is an attractive source for clinical proteomics. However, many proteomic studies have had only limited impact, due factors such as modest numbers subjects, absence disease controls, small defined biomarkers, diversity analytical platforms. Therefore, it difficult merge biomarkers from different into a broadly applicable human urinary proteome database. Ideally, the methodology...
Abstract CE‐MS is a successful proteomic platform for the definition of biomarkers in different body fluids. Besides biomarker defining experimental parameters, CE migration time and molecular weight, especially biomarker's sequence identity an indispensable cornerstone deeper insights into pathophysiological pathways diseases or made‐to‐measure therapeutic drug design. Therefore, this report presents detailed discussion peptide sequencing platforms consisting high performance separation...
Telomere dysfunction limits the proliferative capacity of human cells by activation DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in vast majority tissues during aging, and is accelerated chronic diseases that increase rate cell turnover. Yet, functional role aging remains under debate. Here, we identified marker proteins (i.e., CRAMP, stathmin, EF-1α, chitinase) are secreted from telomere-dysfunctional bone-marrow late generation telomerase...
Abstract Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes CC from nonmalignant lesions. used capillary electrophoresis mass spectrometry (CE-MS) identify disease-specific peptide patterns choledocholithiasis (n = 16), PSC 18), 16) training set. A model for...
Abstract Purpose : Urine proteomics is emerging as a powerful tool for biomarker discovery. The purpose of this study the development well‐characterized “real life” sample that can be used reference standard in urine clinical studies. Experimental design We report on generation male and female samples are extensively characterized by different platforms methods (CE‐MS, LC‐MS, LC‐MS/MS, 1‐D gel analysis combination with nano‐LC MS/MS (using LTQ‐FT ultra), 2‐DE‐MS) their proteome peptidome. In...
Only 30% of patients with elevated serum prostate specific antigen (PSA) levels who undergo biopsy are diagnosed cancer (PCa). Novel methods needed to reduce the number unnecessary biopsies. We report on identification and validation a panel 12 novel biomarkers for (PCaP), using CE coupled MS. The could be defined by comparing first void urine 51 men PCa 35 negative biopsy. In contrast, midstream samples did not allow discriminatory molecules, suggesting that prostatic fluids may source...
Preeclampsia is a major determinant of fetal and maternal morbidity mortality. We used proteomic strategy to identify urinary biomarkers that predict preeclampsia before the onset disease. prospectively collected urine samples from women throughout pregnancy. Samples gestational weeks 12 16 (n=45), 20 (n=50), 28 (n=18) who subsequently had develop were matched controls (n=86, n=49, n=17, respectively). performed capillary electrophoresis online coupled micro-time-of-flight mass spectrometry....
Background Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For of diabetic nephropathy (DN), urinary was successfully applied pilot study. The validity the previously established proteomic biomarkers with respect to diagnostic prognostic potential assessed on separate set patients recruited at three different European centers. In this case-control study 148 Caucasian diabetes mellitus type 2 duration ≥5 years, cases DN were defined...
Background Today, dementias are diagnosed late in the course of disease. Future treatments have to start earlier disease process avoid disability requiring new diagnostic tools. The objective this study is develop a method for differential diagnosis and identification biomarkers Alzheimer's (AD) using capillary-electrophoresis coupled mass-spectrometry (CE-MS) assess potential early AD. Methods Findings Cerebrospinal fluid (CSF) 159 out-patients memory-clinic at University Hospital suffering...
Background. Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase urinary albumin excretion (UAE). However, these markers are considered either to be late-stage or have low sensitivity specificity. In this study, we investigated the performance of proteome-based classifier CKD273, compared with UAE, number different narrow ranges CKD severity, each range separated eGFR 10 mL/min/1.73 m2. Methods. A total...
In this study, we have developed Proteasix, an open-source peptide-centric tool that can be used to predict in silico the proteases involved naturally occurring peptide generation. We a curated cleavage site (CS) database, containing 3500 entries about human protease/CS combinations. On top of built tool, which allows CS retrieval and protease associations from list peptides. To establish proof concept approach, 1388 peptides identified urine samples, compared prediction analysis 1003...
Diabetic nephropathy (DN) is one of the major late complications diabetes. Treatment aimed at slowing down progression DN available but methods for early and definitive detection are currently lacking. The 'Proteomic prediction Renin angiotensin aldosterone system Inhibition prevention Of diabetic nephRopathy In TYpe 2 patients with normoalbuminuria trial' (PRIORITY) aims to evaluate in type diabetes (T2D) using a urinary proteome-based classifier (CKD273).In this ancillary study recently...
Chronic kidney disease (CKD) is part of a number systemic and renal diseases may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis management CKD. We hypothesised that combining metabolomic proteomic approaches could generate more complete view mechanisms. To test this approach, we examined samples from cohort 49 patients representing different stages Urine were analysed for changes using capillary electrophoresis-mass spectrometry urine plasma mass...
Early prevention of diabetic nephropathy is not successful as early interventions have shown conflicting results, partly because a lack and precise indicators disease development. Urinary proteomics has promise in this regard could identify those at high risk who might benefit from treatment. In study we investigate its utility large type 2 cohort with normoalbuminuria. We performed post hoc analysis the Diabetic Retinopathy Candesartan Trials (DIRECT-Protect study), multi centric randomized...
In spite of its invasive nature and risks, kidney biopsy is currently required for precise diagnosis many chronic diseases (CKDs). Here, we explored the hypothesis that analysis urinary proteome can discriminate different types CKD irrespective underlying mechanism disease.We used data from analyses 1180 urine samples patients with CKD, generated by capillary electrophoresis coupled to mass spectrometry. A set 706 served as discovery cohort, 474 were independent validation. For each type,...
Abstract Purpose : Human urine is an ideal candidate for use in clinical diagnostics. It easily available, as untrained personnel can collect it. correlates well with the pathophysiology of a number diseases, making it useful source proteomics. Experimental design In this article, we give update human urinary peptide database derived from over 13 000 data sets CE‐MS by now. Results Urine samples both patients and healthy subjects were analyzed CE‐MS; these included 47 different...