A5102853627- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neural Engineering
- Zebrafish Biomedical Research Applications
- Nerve injury and regeneration
- Microfluidic and Bio-sensing Technologies
- Developmental Biology and Gene Regulation
- Spinal Cord Injury Research
- Analog and Mixed-Signal Circuit Design
- Genomics and Rare Diseases
- Single-cell and spatial transcriptomics
- Genomic variations and chromosomal abnormalities
- 3D Printing in Biomedical Research
- Biomedical Ethics and Regulation
- Genetic Associations and Epidemiology
- Cellular transport and secretion
- Hearing, Cochlea, Tinnitus, Genetics
- RNA regulation and disease
- Parkinson's Disease Mechanisms and Treatments
- Piezoelectric Actuators and Control
- CCD and CMOS Imaging Sensors
- Cancer-related molecular mechanisms research
- Lysosomal Storage Disorders Research
- Advanced Fluorescence Microscopy Techniques
- Virus-based gene therapy research
Rice University
2024-2025
Howard Hughes Medical Institute
2023-2024
Baylor College of Medicine
2022-2024
Neurological Research Institute
2023-2024
Texas Children's Hospital
2023-2024
Gladstone Institutes
2015-2021
University of California, San Francisco
2015-2017
Washington University in St. Louis
2013-2016
Georgia Institute of Technology
2014-2015
Axial elongation of the neural tube is crucial during mammalian embryogenesis for anterior-posterior body axis establishment and subsequent spinal cord development, but these processes cannot be interrogated directly in humans as they occur post-implantation. Here, we report an organoid model extension derived from human pluripotent stem cell (hPSC) aggregates that have been caudalized with Wnt agonism, enabling them to recapitulate aspects morphological temporal gene expression patterns...
Highlights•ITSN1 haploinsufficiency confers a ∼10-fold increased risk of Parkinson's disease (PD)•Effect size surpasses other well-established loci, including GBA1 and LRRK2•In vivo in vitro studies suggest an interaction between ITSN1 α-synuclein•Findings implicate synaptic vesicle trafficking dysfunction PD pathogenesisSummaryDespite its significant heritability, the genetic basis (PD) remains incompletely understood. Here, analyzing whole-genome sequence data from 3,809 cases 247,101...
In this paper, we present a fully integrated multi-modality CMOS cellular sensor array with four sensing modalities to characterize different cell physiological responses, including extracellular voltage recording, impedance mapping, optical detection shadow imaging and bioluminescence sensing, thermal monitoring. The consists of nine parallel pixel groups corresponding signal conditioning blocks. Each group comprises one temperature 16 tri-modality pixels, while each can be independently...
Significance Spinal cord injury (SCI) significantly disrupts normal neural circuitry, leading to severe degradation of motor and sensory function. Excitatory interneurons that relay signals from the brain networks throughout spinal cord, including glutamatergic V2a coordinate respiration locomotion, are lost after SCI. Thus, transplantation SCI could provide a novel therapy restore functional connections between spared downstream neurons. This study describes generation human pluripotent...
Embryonic stem (ES) cells can be differentiated into many neural cell types that hold great potential as replacement therapies following spinal cord injury (SCI). Coupling transplantation with biomaterial scaffolds produce a unified combination therapy several advantages including enhanced survival, greater transplant retention, reduced scarring, and improved integration at the transplant/host interface. Undesired types, however, are commonly present in ES-cell derived cultures due to...
Proneural transcription factors establish molecular cascades to orchestrate neuronal diversity. One such factor, Atonal homolog 1 (Atoh1), gives rise cerebellar excitatory neurons and over 30 distinct nuclei in the brainstem critical for hearing, breathing, balance. Although Atoh1 lineage have been qualitatively described, transcriptional programs that drive their fate decisions full extent of diversity remain unknown. Here, we analyzed single-cell RNA sequencing ATOH1 DNA binding developing...
Abstract The unprecedented scale of genomic databases has revolutionized our ability to identify regions in the human genome intolerant variation—regions often implicated disease. However, these datasets remain constrained by limited ancestral diversity. Here, we analyze whole-exome sequencing data from 460,551 UK Biobank and 125,748 Genome Aggregation Database (gnomAD) participants across multiple ancestries test several key intolerance metrics, including Residual Variance Intolerance Score...
V2a interneurons of the ventral spinal cord and hindbrain play an important role in central pattern generators (CPGs) involved locomotion, skilled reaching, respiration. However, sources for vitro studies are limited. In this study, we developed a differentiation protocol from mouse embryonic stem cells (mESCs). Cells were induced 2(-)/4(+) induction with varying concentrations retinoic acid (RA) mild sonic hedgehog (Shh) agonist purmorphamine (Pur) order to increase expression interneuron...
ABSTRACT A common problem with using embryonic stem (ES) cells as a source for analysis of gene expression, drug toxicity, or functional characterization studies is the heterogeneity that results from many differentiation protocols. The ability to generate large numbers high purity differentiated pluripotent could greatly enhance their utility in vitro and transplantation pre‐clinical injury models. Population particularly troublesome post‐mitotic neurons, including motoneurons, because they...
Abstract Background Despite its significant heritability, the genetic underpinnings of Parkinson disease (PD) remain incompletely understood, particularly role rare variants. Advances in population-scale sequencing now provide an unprecedented opportunity to uncover additional large-effect risk factors and expand our understanding mechanisms. Methods We leveraged whole-genome sequence data with linked electronic health records from 490,560 UK Biobank participants, identifying 3,809 PD cases...
Cell-based assays are powerful tools to characterize cell- or tissue-specific physiological behaviors under external biochemical stimuli. External stimuli trigger endogenous cellular mechanisms that produce a cascade of changes, resulting in easily measurable signals. widely used for large-scale drug screening the pharmaceutical industry, where vitro cultured cells potency and toxicity thousands chemicals, leading new development. This is particularly relevant individualized medicine as...
The spinal cord contains a diverse array of sensory and motor circuits that are essential for normal function. Spinal injury (SCI) permanently disrupts neural through initial mechanical damage, as well cascade secondary events further expand the lesion, resulting in permanent paralysis. Tissue clearing 3D imaging have recently emerged promising techniques to improve our understanding complex circuitry changes result from damage due SCI. However, application this technology studying intact...
Pontine nuclei (PN) neurons mediate the communication between cerebral cortex andthe cerebellum to refine skilled motor functions. Prior studies showed that PN fall into two subtypes based on their anatomic location and region-specific connectivity, but extent of heterogeneity its molecular drivers remain unknown. Atoh1 encodes a transcription factor is expressed in precursors. We previously partial loss function mice results delayed development impaired learning. In this study, we performed...
This paper focuses on CMOS biosensor technologies for cellular biosensing applications. We first present our to achieve on-CMOS cell culture, maintenance, and differentiation, as the basis biosensors. Next, we introduce a frequency-shift magnetic sensor scheme which performs detections without post-processing or external biasing field. Finally, will demonstrate based achieves real-time chemical detections; such can be utilized massively paralleled high-throughput screening in drug development.
Summary Rapidly expanding genomic databases have enabled the identification of regions in human genome intolerant to variation and thus likely relevant disease. However, despite their unprecedented scale, these datasets remain constrained by limited ancestral diversity. Here, we systematically evaluate how genetic diversity impacts gene- sub-genic intolerance metrics analyzing whole-exome sequencing data from 460,551 UK Biobank participants 125,748 gnomAD across diverse backgrounds. Through...
We propose to perform a live demonstration on our recently developed multi-modality CMOS sensor array whose pixel each integrates several biosensors with different sensing modalities. Unlike many single-modality sensors, this can real-time capture multi-physics responses of living cells and tissues high spatiotemporal resolution. This will showcase the operation its detection human ovarian cancer HeyA8-F8 under chemical administrations.
Abstract The spinal cord contains a diverse array of sensory and motor circuits that are essential for normal function. Spinal injury (SCI) permanently disrupts neural through initial mechanical damage, as well cascade secondary events further expand the lesion, resulting in permanent paralysis. Tissue clearing 3D imaging have recently emerged promising techniques to improve our understanding complex circuitry changes result from damage due SCI. However, application this technology studying...