A5001281377- Pharmacogenetics and Drug Metabolism
- Innovative Microfluidic and Catalytic Techniques Innovation
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Statistical Methods in Clinical Trials
- Nuclear Receptors and Signaling
- Computational Drug Discovery Methods
- CRISPR and Genetic Engineering
- Nerve injury and regeneration
- Cholinesterase and Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- Genomics and Phylogenetic Studies
- Renal Transplantation Outcomes and Treatments
- Biosimilars and Bioanalytical Methods
- Cancer Genomics and Diagnostics
- RNA regulation and disease
- Dementia and Cognitive Impairment Research
- Biosensors and Analytical Detection
- Environmental DNA in Biodiversity Studies
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- Attention Deficit Hyperactivity Disorder
Seattle Children's Hospital
2025
University of Washington
2021-2024
University of Minnesota
2017-2024
Oligomeric forms of amyloid-forming proteins are believed to be the principal initiating bioactive species in many neurodegenerative disorders, including Alzheimer's disease (AD). Amyloid-β (Aβ) oligomers implicated AD-associated phosphorylation and aggregation microtubule-associated protein tau. To investigate specific molecular pathways activated by different assemblies, we isolated various Aβ from Tg2576 mice, which a model for AD. We found that Aβ*56, 56-kDa oligomer is detected before...
Mounting evidence indicates that soluble oligomeric forms of amyloid proteins linked to neurodegenerative disorders, such as amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major deleterious species for neuronal function in these diseases. Here, we found an abnormal accumulation αSyn AD brains by custom ELISA, size-exclusion chromatography, and nondenaturing/denaturing immunoblotting techniques. Importantly, abundance oligomers human brain tissue correlated with cognitive impairment...
Stem cells have lower facultative heterochromatin as defined by trimethylation of histone H3 lysine 27 (H3K27me3) compared to differentiated cells. However, the mechanisms underlying these differential H3K27me3 levels remain elusive. Because are diluted 2-fold in every round replication and then restored through rest cell cycle, we reasoned that cycle length could be a key regulator total levels. Here, propose short G1 phase restricts stem To test this model, determined changes mouse...
Abstract The Cytochrome P450s (CYPs) enzyme family metabolizes ∼80% of small molecule drugs. Variants in CYPs can substantially alter drug metabolism, leading to improper dosing and severe adverse reactions. Due low sequence conservation, predicting variant effects across is challenging. Even closely related like CYP2C9 CYP2C19, which share 92% amino acid identity, display distinct phenotypic properties. Using Variant Abundance by Massively Parallel sequencing (VAMP-seq), we measured the...
As costs of next-generation sequencing decrease, identification genetic variants has far outpaced our ability to understand their functional consequences. This lack understanding is a central challenge key promise pharmacogenomics: using information guide drug selection and dosing. Recently developed multiplexed assays variant effect enable experimental measurement the function thousands simultaneously. Here, we describe that have been performed on nearly 25,000 in eight pharmacogenes (...
Stem cells have lower facultative heterochromatin as defined by trimethylation of histone H3 lysine 27 (H3K27me3) compared to differentiated cells. However, the mechanisms underlying these differential H3K27me3 levels remain elusive. Because are diluted two-fold in every round replication and then restored through rest cell cycle, we reasoned that cycle length could be a key regulator total levels. Here, propose fast restricts stem To test this model, determined changes mESCs globally at...
ABSTRACT CYP2C9 encodes a cytochrome P450 enzyme responsible for metabolizing up to 15% of small molecule drugs, and variants can alter the safety efficacy these therapeutics. In particular, anti-coagulant warfarin is prescribed over 15 million people annually polymorphisms in affect patient response leading an increased risk hemorrhage. We developed Click-seq, pooled yeast-based activity assay test thousands variants. Using we measured 6,142 missense expressed yeast. also steady-state...
Abstract Antisense oligonucleotide (ASO) therapy for neurological disease has been successful in clinical settings and its potential generated hope Alzheimer’s (AD). We previously described that ablating SNCA encoding α-synuclein (αSyn) a mouse model of AD was beneficial. Here, we sought to demonstrate whether transient reduction αSyn expression using ASO could be therapeutic AD. The efficacy the measured via immunocytochemistry, RT-qPCR western blotting. To assess spatial learning memory,...
Long-read sequencing technologies, an attractive solution for many applications, often suffer from higher error rates. Alignment of multiple reads can improve base-calling accuracy, but some e.g. mutagenized libraries where distinct clones differ by one or few variants, require the use barcodes unique molecular identifiers. Unfortunately, errors interfere with correct barcode identification, and a given sequence may be linked to independent within library.
Abstract Cytochrome P450s (CYPs) are a family of enzymes responsible for metabolizing nearly 80% small molecule drugs. Variants in CYPs can substantially alter drug metabolism, which may result improper dosing and severe adverse reactions. have low sequence conservation, making it difficult to anticipate whether variant effects measured one CYP extend others based on alone. Even closely related CYPs, like CYP2C9 its closest homolog CYP2C19, distinct phenotypic properties despite sharing 92%...
Long read sequencing technologies, an attractive solution for many applications, often suffer from higher error rates. Alignment of multiple reads can improve base-calling accuracy, but some e.g. mutagenized libraries where distinct clones differ by one or few variants, require the use barcodes unique molecular identifiers. Unfortunately, errors interfere with correct barcode identification, and a given sequence may be linked to independent within library. Here we focus on target application...