A5043463578- Pharmacogenetics and Drug Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Chemotherapy-induced cardiotoxicity and mitigation
- 3D Printing in Biomedical Research
- Liver physiology and pathology
- Receptor Mechanisms and Signaling
- Eicosanoids and Hypertension Pharmacology
- Bioinformatics and Genomic Networks
- Nutrition, Genetics, and Disease
- Estrogen and related hormone effects
- Eosinophilic Disorders and Syndromes
- Pancreatic function and diabetes
- Micro and Nano Robotics
- Biosimilars and Bioanalytical Methods
- Epigenetics and DNA Methylation
- Microfluidic and Capillary Electrophoresis Applications
- Metabolomics and Mass Spectrometry Studies
- Urticaria and Related Conditions
- Artificial Immune Systems Applications
- Hormonal Regulation and Hypertension
- Pediatric Hepatobiliary Diseases and Treatments
- Tissue Engineering and Regenerative Medicine
- Mast cells and histamine
- Renal and related cancers
- Protein purification and stability
Roche (Switzerland)
2017-2024
BC Cancer Agency
2013
Canada's Michael Smith Genome Sciences Centre
2013
Abstract Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, FDA classified DMSO safest solvent category. became widely used many biomedical fields and biological effects were overlooked. Meanwhile, science has evolved towards sensitive high-throughput techniques new research areas, including epigenomics microRNAs. Considering its wide use, especially cryopreservation vitro assays, we evaluated effect using these technological...
Abstract Uncovering cellular responses from heterogeneous genomic data is crucial for molecular medicine in particular drug safety. This can be realized by integrating the activities networks of interacting proteins. As proof-of-concept we challenge network modeling with time-resolved proteome, transcriptome and methylome measurements iPSC-derived human 3D cardiac microtissues to elucidate adverse mechanisms anthracycline cardiotoxicity measured four different drugs (doxorubicin, epirubicin,...
Abstract Selective binding of TCR-like antibodies that target a single tumour-specific peptide antigen presented by human leukocyte antigens (HLA) is the absolute prerequisite for their therapeutic suitability and patient safety. To date, selectivity assessment has been limited to library screening predictive modeling. We developed an experimental platform de novo identify interactomes directly in tissues using mass spectrometry. As proof concept, we confirm epitope MAGE-A4-specific...
Doxorubicin (DOX) is a chemotherapeutic agent of which the medical use limited due to cardiotoxicity. While acute cardiotoxicity reversible, chronic persistent or progressive, dose-dependent and irreversible. DOX mechanisms action are not fully understood yet, 3 toxicity processes known occur in vivo: cardiomyocyte dysfunction, mitochondrial dysfunction cell death. We present an vitro experimental design aimed at detecting DOX-induced by obtaining global view induced molecular through...
Three-dimensional liver in vitro systems have recently attracted a lot of attention drug development. These help to gain unprecedented insights into drug-induced injury (DILI), as they more closely reproduce biology, and effects can be studied isolated controllable microenvironments. Many groups established human-based models but so far neglected the animal equivalent, although availability both would desirable. Animal enable back- forward translation vivo findings, bridge gap between rodent...
Do differences in heritable genetic factors explain some of the difference age at natural menopause (ANM) among populations? One single nucleotide polymorphism (SNP)-ANM association (rs16991615) detected European women was replicated Iranian women. Genetics plays an important role ANM, and well-powered genome-wide studies (GWAS) ANM performed have discovered many statistically significant SNP-ANM associations. Average varies by ethnicity, population-specific ANM-associated alleles may part...
Abstract The data currently described was generated within the EU/FP7 HeCaToS project ( He patic and Ca rdiac To xicity S ystems modeling). aimed to develop an in silico prediction system contribute drug safety assessment for humans. For this purpose, multi-omics of repeated dose toxicity were obtained 10 hepatotoxic cardiotoxic compounds. Most gained from vitro experiments which 3D microtissues (either hepatic or cardiac) exposed a therapeutic (physiologically relevant concentrations...
Basimglurant (RG7090), a small molecule under development to treat certain forms of depression, demonstrated foci altered hepatocytes in long-term rodent-toxicity study. Additional evidence pointed toward the activation constitutive androstane receptor (CAR), an established promoter nongenotoxic and rodent-specific hepatic tumors. This mode action potential human relevance was explored vivo using rodent cynomolgus monkey models vitro murine liver spheroids. Wild type (WT) CAR/pregnane X...
We present a generic workflow combining physiology-based computational modeling and in vitro data to assess the clinical cholestatic risk of different drugs systematically. Changes expression levels genes involved enterohepatic circulation bile acids were obtained from an assay mimicking 14 days repeated drug administration for 10 marketed drugs. These changes gene over time contextualized acid model glycochenodeoxycholic acid. The simulated drug-induced response concentrations was then...