Ryan G. Lim
A5007501340- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Neurogenetic and Muscular Disorders Research
- Ubiquitin and proteasome pathways
- Genomics and Phylogenetic Studies
- Epigenetics and DNA Methylation
- Mesenchymal stem cell research
- Autophagy in Disease and Therapy
- Collagen: Extraction and Characterization
- 3D Printing in Biomedical Research
- Electrospun Nanofibers in Biomedical Applications
- Silk-based biomaterials and applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Antibiotic Resistance in Bacteria
- Muscle Physiology and Disorders
- Bacterial Identification and Susceptibility Testing
- Tissue Engineering and Regenerative Medicine
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- Clinical Reasoning and Diagnostic Skills
- Radiology practices and education
- Skin and Cellular Biology Research
University of California, Irvine
2016-2024
Chan Zuckerberg Initiative (United States)
2024
Nova Southeastern University
2024
University of California, San Francisco
2024
McMaster University
2024
Berkeley College
2024
University of California, Berkeley
2024
Agency for Science, Technology and Research
2021-2024
Bioprocessing Technology Institute
2024
Cedars-Sinai Medical Center
2024
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves functionally compromised to promote dysfunction. Further, underlying mechanisms remain elusive given limitations with mouse models post-mortem tissue identify primary deficits. We undertook a transcriptome...
Answer ALS is a biological and clinical resource of patient-derived, induced pluripotent stem (iPS) cell lines, multi-omic data derived from iPS neurons longitudinal smartphone over 1,000 patients with ALS. This provides population-level that may be employed to identify clinical-molecular-biochemical subtypes amyotrophic lateral sclerosis (ALS). A unique smartphone-based system was collect deep data, including fine motor activity, speech, breathing linguistics/cognition. The spinal were...
Using induced pluripotent stem cells (iPSCs) to understand the mechanisms of neurological disease holds great promise; however, there is a lack well-curated lines from large array participants. Answer ALS has generated over 1,000 iPSC control and amyotrophic lateral sclerosis (ALS) patients along with clinical whole-genome sequencing data. The current report summarizes cell marker gene expression in motor neuron cultures derived 92 healthy 341 participants using 32-day differentiation...
Chronic cellular stress associated with neurodegenerative disease can result in the persistence of granule (SG) structures, membraneless organelles that form response to stress. In Huntington's (HD), chronic expression mutant huntingtin generates various forms stress, including activation unfolded protein and oxidative However, it has yet be determined whether SGs are a feature HD neuropathology. We examined miRNA composition extracellular vesicles (EVs) present cerebrospinal fluid (CSF)...
ABSTRACT Metagenomics has enabled the rapid, unbiased detection of microbes across diverse sample types, leading to exciting discoveries in infectious disease, microbiome, and viral research. However, analysis metagenomic data is often complex computationally resource-intensive. CZ ID a free, cloud-based genomic platform that enables researchers detect using data, identify antimicrobial resistance genes, generate consensus genomes. With ID, can upload raw sequencing find matches NCBI...
Creating a cDNA library for deep mRNA sequencing (mRNAseq) is generally done by random priming, creating multiple fragments along each transcript. A 3'-end-focused approach cannot detect differential splicing, but has potentially higher throughput at lower cost, with the ability to improve quantification using transcript molecule counting unique molecular identifiers (UMI) that correct PCR bias. Here, we compare an implementation of such 3'-digital gene expression (3'-DGE) "conventional"...
Aberrant neuronal development and the persistence of mitotic cellular populations have been implicated in a multitude neurological disorders, including Huntington's disease (HD). However, mechanism underlying this potential pathology remains unclear. We used modified protocol to differentiate induced pluripotent stem cells (iPSCs) from HD patients unaffected controls into cultures enriched for medium spiny neurons, cell type most affected HD. performed single-cell bulk transcriptomic...
DNA damage repair genes are modifiers of disease onset in Huntington's (HD), but how this process intersects with associated pathways remains unclear. Here we evaluated the mechanistic contributions protein inhibitor activated STAT-1 (PIAS1) HD mice and patient-derived induced pluripotent stem cells (iPSCs) find a link between PIAS1 pathways. We show that is component transcription-coupled complex, includes end processing enzyme polynucleotide kinase-phosphatase (PNKP), SUMO E3 ligase for...
Abstract The complexity of affected brain regions and cell types is a challenge for Huntington’s disease (HD) treatment. Here we use single nucleus RNA sequencing to investigate molecular pathology in the cortex striatum from R6/2 mice human HD post-mortem tissue. We identify type-specific -agnostic signatures suggesting oligodendrocytes (OLs) oligodendrocyte precursors (OPCs) are arrested intermediate maturation states. OL-lineage regulators OLIG1 OLIG2 negatively correlated with CAG length...
Abstract The clinical presentation of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, varies widely across patients, making it challenging to determine if potential therapeutics slow progression. We sought whether there were common patterns disease progression that could aid in the design and analysis trials. developed an approach based on mixture Gaussian processes identify clusters patients sharing similar patterns, modeling their average trajectories variability...
Altered cellular metabolism is believed to be an important contributor pathogenesis of the neurodegenerative disorder Huntington's disease (HD). Research has primarily focused on mitochondrial toxicity, which can cause death vulnerable striatal neurons, but other aspects have also been implicated. Most previous studies carried out using postmortem human brain or non-human cells. Here, we studied bioenergetics in induced pluripotent stem cell-based model disease. We found decreased adenosine...
Neurodegenerative diseases are challenging for systems biology because of the lack reliable animal models or patient samples at early disease stages. Induced pluripotent stem cells (iPSCs) could address these challenges. We investigated DNA, RNA, epigenetics, and proteins in iPSC-derived motor neurons from patients with ALS carrying hexanucleotide expansions
Amyotrophic Lateral Sclerosis (ALS), like many other neurodegenerative diseases, is highly heritable, but with only a small fraction of cases explained by monogenic disease alleles. To better understand sporadic ALS, we report epigenomic profiles, as measured ATAC-seq, motor neuron cultures derived from diverse group 380 ALS patients and 80 healthy controls. We find that chromatin accessibility heavily influenced sex, the iPSC cell type origin, ancestry, inherent variance arising sequencing....
Understanding the normal function of Huntingtin (HTT) protein is significance in design and implementation therapeutic strategies for Huntington’s disease (HD). Expansion CAG repeat HTT gene, encoding an expanded polyglutamine (polyQ) within protein, causes HD may compromise HTT’s activity contributing to pathology. Here, we investigated previously defined role autophagy specifically through studying association with ubiquitin. We find that interacts directly ubiquitin vitro. Tandem affinity...
Significance Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by expansion of polyglutamine repeat within the huntingtin (HTT) protein. A normal function HTT that scaffold for selective autophagy, mechanism protein and organelle degradation lysosome required neuronal health. Here, we show inflammatory IκB kinase (IKK) subunit IKKβ may in vivo to regulate autophagy through direct phosphorylation at serine 13 activation gene expression. slow HD behavioral...
Huntington disease (HD) is a neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene that alters cellular homeostasis, particularly striatum and cortex. Astrocyte signaling establishes maintains neuronal functions are often altered under pathological conditions. We performed single-nuclei RNA-sequencing on human HD patient-induced pluripotent stem cell (iPSC)-derived astrocytes striatal cortical tissue from R6/2 mice to investigate high-resolution astrocyte state...
The National Institute of Health (NIH) Library integrated network-based cellular signatures (LINCS) program is premised on the generation a publicly available data resource cell-based biochemical responses or "signatures" to genetic environmental perturbations. NeuroLINCS uses human inducible pluripotent stem cells (hiPSCs), derived from patients and healthy controls, differentiated into motor neuron cell cultures. This multi-laboratory effort strives establish i) robust multi-omic workflows...
Huntington's disease (HD), a genetic neurodegenerative disorder, primarily affects the striatum and cortex with progressive loss of medium-sized spiny neurons (MSNs) pyramidal neurons, disrupting cortico-striatal circuitry. A promising regenerative therapeutic strategy transplanting human neural stem cells (hNSCs) is challenged by need for long-term functional integration. We previously described that, short-term hNSC transplantation into HD R6/2 mice, differentiated electrophysiologically...