A5045362081- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Olfactory and Sensory Function Studies
- Biochemical Analysis and Sensing Techniques
- T-cell and B-cell Immunology
- Renal and related cancers
- Sperm and Testicular Function
- Prenatal Screening and Diagnostics
- Biosensors and Analytical Detection
- Molecular Biology Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Neurobiology and Insect Physiology Research
- Mycobacterium research and diagnosis
- Family and Disability Support Research
- CAR-T cell therapy research
- Receptor Mechanisms and Signaling
- Reproductive Biology and Fertility
- RNA Interference and Gene Delivery
University of California, San Diego
2011-2020
BD Biosciences (United States)
2018-2019
Johns Hopkins Medicine
2009
Johns Hopkins University
2009
For vertebrate olfactory signal transduction, a calcium-activated chloride conductance serves as major amplification step. However, the molecular identity of channel (CaCC) is unknown. Here we report proteomic screen for cilial membrane proteins mouse sensory neurons (OSNs) that identified all known transduction components well Anoctamin 2 (ANO2). Ano2 transcripts were expressed specifically in OSNs epithelium, and ANO2::EGFP fusion protein localized to OSN cilia when vivo using an...
The mechanisms dictating whether a cell proliferates or differentiates have undergone intense scrutiny, but they remain poorly understood. Here, we report that UPF1, central component in the nonsense-mediated RNA decay (NMD) pathway, plays key role this decision by promoting proliferative, undifferentiated state. UPF1 acts, part, destabilizing NMD substrate encoding TGF-β inhibitor SMAD7 and stimulating signaling. also promotes of mRNAs many other proteins oppose Neural differentiation is...
Gene duplication is a major evolutionary force driving adaptation and speciation, as it allows for the acquisition of new functions can augment or diversify existing functions. Here, we report gene event that yielded another outcome--the generation antagonistic One product this event--UPF3B--is critical nonsense-mediated RNA decay (NMD) pathway, while its autosomal counterpart--UPF3A--encodes an enigmatic protein previously shown to have trace NMD activity. Using loss-of-function approaches...
The developmental origins of most adult stem cells are poorly understood. Here, we report the identification a transcription factor—RHOX10—critical for initial establishment spermatogonial (SSCs). Conditional loss entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, phenotype indistinguishable from caused by only Rhox10. We demonstrate this results dramatically reduced SSC generation. By using battery approaches, including...
Testis-expressed X-linked genes typically evolve rapidly. Here, we report on a testis-expressed microRNA (miRNA) cluster that despite rapid alterations in sequence has retained its position the Fragile-X region of X chromosome placental mammals. Surprisingly, miRNAs encoded by this (Fx-mir) have predilection for targeting immediately adjacent gene, Fmr1, an unexpected finding given usually act trans, not cis Robust repression Fmr1 is conferred combinations Fx-mir induced Sertoli cells (SCs)...
The UPF3B-dependent branch of the nonsense-mediated RNA decay (NMD) pathway is critical for human cognition. Here, we examined role UPF3B in olfactory system. Single-cell RNA-sequencing (scRNA-seq) analysis demonstrated considerable heterogeneity sensory neuron (OSN) cell populations wild-type (WT) mice, and revealed that loss influences specific subsets these populations. also regulates expression a large cadre antimicrobial genes OSNs, promotes selection receptor (
Digital PCR (dPCR) was first conceived for single-molecule quantitation. However, current dPCR systems often require DNA templates to share partitions due limited partitioning capacities. Here, we introduce UltraPCR, a next-generation system where counting is performed in regimen through 6-log dynamic range using swift and parallelized workflow. Each UltraPCR reaction divided into >30 million without microfluidics achieve single template occupancy. Combined with unique emulsion chemistry,...
Olfactory receptor (Olfr) genes comprise the largest gene family in mice. Despite their importance olfaction, how most Olfr mRNAs are regulated remains unexplored. Using RNA-seq analysis coupled with of pre-existing databases, we found that have several atypical features suggesting post-transcriptional regulation impacts expression. First, mRNAs, as a group, dramatically higher average AU-content and lower predicted secondary structure than do control mRNAs. Second, density AU-rich elements...
ABSTRACT PCR has been a reliable and inexpensive method for nucleic acid detection in the past several decades. In particular, multiplex is powerful tool to analyze many biomarkers same reaction, thus maximizing sensitivity reducing sample usage. However, balancing amplification kinetics between amplicons distinguishing them can be challenging, diminishing broad adoption of high order panels. Here, we present new paradigm multiplexed using UltraPCR. UltraPCR utilizes simple centrifugation...
Abstract Single-Cell mRNA sequencing has enhanced our knowledge of the cell populations found in individual tissues or disease states. However, low correlation between and protein expression levels hinders understanding biology disease. Traditional single assays are limited number parameters that can be achieved within one experiment. Here we use oligo-conjugated antibodies (Ab-seq) combination with massively parallel on BD Rhapsody™ platform to simultaneously measure content human blood...
To address the physiological role of nonsense‐mediated RNA decay (NMD), we generated mice with a null mutation in Upf3b NMD gene. While these Upf3b‐null are viable, fertile, and grossly normal, battery behavioral tests revealed they exhibit specific defect sensorimotor gating. This is commonly displayed Schizophrenia patients, subset whom have recently been shown by several groups to mutations human UPF3B Neuropathological examination frontal cortex, site responsible for gating, decreased...
Nonsense‐mediated RNA decay (NMD) was originally identified to degrade “nonsense” mRNAs, but since then it has become clear that also regulates ~10% of wild‐type transcripts. This regulatory role suggests NMD itself is subject regulation. Indeed, we recently a conserved circuit in mature neurons through the ability microRNA miR‐128 repress factors UPF1 and MLN51. Here, report identification another miR‐9, which expressed during neurogenesis, by targeting UPF3B. Loss UPF3B shown cause...
MicroRNAs (miRNAs) are small regulatory molecules with diverse roles in many biological systems. Most studies to date have focused on the function of conserved miRNAs. In contrast, little is known about rapidly evolving miRNAs despite their preponderance some systems, including reproductive tract. Here, we asked whether changed target repertoire different species or they co‐evolved targets maintain regulation. As a model system address this question, used set X‐linked miRNA genes selectively...
Abstract CD4 T cells are critical components of the adaptive immune system and can differentiate into specialized effector subsets to mediate response against a wide host pathogens. Studying transcriptional profile distinct helper has illuminated important pathways mechanisms for cell function lineage. Recently, single whole transcriptome analysis (WTA) provides high resolution view complex highly heterogeneous dynamics populations. However, such methods often labor cost prohibiting...
Abstract The immune system consists of complex gene regulatory networks that allow a rapid transition different cellular states during an response. Cell-surface marker analysis using flow cytometry or single cell RNA-seq has allowed characterization subpopulations and greater understanding the complexity cells. However, restrictions on protein-only RNA-only can greatly limit how genes are regulated in For example, many surface markers - such as CD4 T cells thousands protein copies per...
Abstract Diverse immune populations reside in non-lymphoid organs and contribute to defense tissue homeostasis. However, these cells are often hard study due low cell abundance high heterogeneity. Recent advancements single-cell sequencing technology provides a powerful parameter tool peripheral populations. But current single experiments costly limited by sample throughput. To address limitations, we have developed novel multiplexing approach for throughput sequencing. In this study,...