- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Extracellular vesicles in disease
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Pregnancy and preeclampsia studies
- MicroRNA in disease regulation
- Cannabis and Cannabinoid Research
- Neurotransmitter Receptor Influence on Behavior
- Cell Image Analysis Techniques
- Psychedelics and Drug Studies
- Cancer therapeutics and mechanisms
- interferon and immune responses
- T-cell and B-cell Immunology
- Neuroscience and Neuropharmacology Research
- Antibiotic Resistance in Bacteria
- Pharmacological Receptor Mechanisms and Effects
- Gut microbiota and health
- Drug Transport and Resistance Mechanisms
- Receptor Mechanisms and Signaling
- Bacterial Genetics and Biotechnology
- Immune cells in cancer
- DNA Repair Mechanisms
Stanford University
2020-2024
University of Wisconsin–Madison
2014
Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing biology and enabling new insights into the physiology human organs. We created a reference atlas comprising nearly 500,000 cells from 24 different tissues organs, many same donor. This enabled molecular more than 400 types, their distribution across tissues, tissue-specific variation in gene expression. Using multiple single donor identification clonal T between mutation rate B cells,...
Abstract Liquid biopsies that measure circulating cell-free RNA (cfRNA) offer an opportunity to study the development of pregnancy-related complications in a non-invasive manner and bridge gaps clinical care 1–4 . Here we used 404 blood samples from 199 pregnant mothers identify validate cfRNA transcriptomic changes are associated with preeclampsia, multi-organ syndrome is second largest cause maternal death globally 5 We find gene expression between normotensive preeclamptic marked stable...
Abstract Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept identify cell types origin using the Tabula Sapiens transcriptomic atlas as well individual atlases in combination with Human Protein Atlas consensus dataset. define type signature scores, which allow inference that contribute cell-free for a variety diseases.
Indolethylamine-N-methyltransferase (INMT) is a Class 1 transmethylation enzyme known for its production of N,N-dimethyltryptamine (DMT), hallucinogen with affinity various serotonergic, adrenergic, histaminergic, dopaminergic, and sigma-1 receptors. DMT produced via the action INMT on endogenous substrates tryptamine S-adenosyl-l-methionine (SAM). The biological, biochemical, selective small molecule regulation activity remain largely unknown. Kinetic mechanisms inhibition rabbit lung...
Abstract Cell-free RNA (cfRNA) can be used to noninvasively measure dynamic and longitudinal physiological changes throughout the body. While there is considerable effort in liquid biopsy field determine disease tissue-of-origin, pathophysiology occurs at cellular level. Here, we describe two approaches identify cell type contributions cfRNA. First Tabula Sapiens , a transcriptomic atlas of human body computationally deconvolve cell-free transcriptome into sum specific transcriptomes, thus...
Abstract Single-cell RNA sequencing (scRNA-seq) enables the detailed examination of a cell’s underlying regulatory networks and molecular factors contributing to its identity. We developed scRFE with goal generating interpretable gene lists that can accurately distinguish observations (single-cells) by their features (genes) given metadata category dataset. is an algorithm combines classical random forest classifier recursive feature elimination cross validation find necessary sufficient...
Early detection of the cell type changes underlying several genitourinary tract diseases largely remains an unmet clinical need, where existing assays, if available, lack cellular resolution afforded by invasive biopsy. While messenger RNA in urine could reflect dynamic signal that facilitates early detection, current measurements primarily detect single genes and thus do not entire transcriptome contributions type-specific RNA.
Maintaining the equilibrium of neurotransmitters (NT) at neural synapses is essential for normal brain functioning. Lack regulation NT levels associated with disorders including depression, Parkinson’s disease, ADHD, and epilepsy. The dopamine transporter (DAT) primary removal mechanism NT, dopamine, from synaptic cleft. reuptake critical preventing chemical imbalance inhibition has become target antidepressants. Drosophila melanogaster DAT was crystallized in complex a tricyclic...
Abstract Liquid biopsies that measure circulating cell-free RNA (cfRNA) offer an unprecedented opportunity to noninvasively study the development of pregnancy-related complications and bridge gaps in clinical care. Here, we used 404 blood samples from 199 pregnant mothers identify validate cfRNA transcriptomic changes are associated with preeclampsia (PE), a multi-organ syndrome which is second largest cause maternal death globally. We find gene expression between normotensive (NT)...
Approximately one disruption in DNA replication occur every cell cycle bacteria leading to partially duplicated chromosomes. Since unfinished can result genome instability and death, need a mechanism reload the machinery onto genome. Known as restart primosome (RRP), several proteins function replicative helicase abandoned forks, restarting replication. PriA is most conserved member of RRP, initiating dominant pathway. A helicase, remodels collapsed forks serves platform for binding other...
Urine is assayed alongside blood in medicine, yet current clinical diagnostic tests utilize only a small fraction of its total biomolecular repertoire, potentially foregoing high-resolution insights into human health and disease. In this work, we characterized the joint landscapes transcriptomic metabolomic signals urine. We also compared urine transcriptome to plasma cell-free RNA, identifying distinct cell type repertoire enrichment for metabolic signal. Untargeted measurements identified...
The treatment of bacterial diseases has become a serious problem in clinical medicine large part because antibiotic resistance. One way bacteria have increased resistance to drugs is the overexpression multidrug efflux pumps, exemplified by AcrAB‐TolC, group three proteins that span both inner and outer membranes E. coli . AcrAB‐TolC transports wide range foreign compounds broad spectrum antibiotics. AcrB forms homo‐trimeric structure uses cyclical conformational changes powered ATP...