Ritchie Ho
A5066327301- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Pluripotent Stem Cells Research
- Axon Guidance and Neuronal Signaling
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Cancer Mechanisms and Therapy
- Spine and Intervertebral Disc Pathology
- Natural Compounds in Disease Treatment
- RNA Research and Splicing
- TGF-β signaling in diseases
- Epigenetics and DNA Methylation
- Immune Response and Inflammation
- Single-cell and spatial transcriptomics
- Nerve injury and regeneration
- Hereditary Neurological Disorders
- Neuroscience and Neural Engineering
- Prion Diseases and Protein Misfolding
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- MicroRNA in disease regulation
- 3D Printing in Biomedical Research
- Kruppel-like factors research
- Developmental Biology and Gene Regulation
Cedars-Sinai Medical Center
2015-2024
Regenerative Medicine Institute
2020-2022
University of California, Los Angeles
2010-2014
California Institute of Technology
2006
Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region C9orf72 gene are most common genetic cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Decreased expression is seen expansion carriers, suggesting that loss function may play role disease. We found two independent mouse lines lacking ortholog (3110043O21Rik) all tissues developed normally aged without motor neuron Instead, null mice progressive splenomegaly lymphadenopathy with accumulation engorged...
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...
Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip) systems designed to emulate microvolume cytoarchitecture enable co-culture distinct cell types. Brain microvascular endothelial cells (BMECs) share common signaling pathways with neurons early development, but their contribution human neuronal maturation is largely unknown. To study this interaction influence microculture,...
Mitofusin-2 (MFN2) is a mitochondrial outer-membrane protein that plays pivotal role in dynamics most tissues, yet mutations MFN2, which cause Charcot-Marie-Tooth disease type 2A (CMT2A), primarily affect the nervous system. We generated transgenic mouse model of CMT2A developed severe early onset vision loss and neurological deficits, axonal degeneration without cell body loss, cytoplasmic accumulations fragmented mitochondria. While aggregates were labeled for mitophagy, mutant MFN2 did...
Abstract Amyotrophic lateral sclerosis is a fatal and incurable neurodegenerative disease that mainly affects the neurons of motor system. Despite increasing understanding its genetic components, their biological meanings are still poorly understood. Indeed, it not clear to which extent pathological features associated with amyotrophic commonly shared by different genes causally linked this disorder. To address point, we combined multiomics analysis covering transcriptional, epigenetic...
Cardiovascular toxicity causes adverse drug reactions and may lead to removal from the pharmaceutical market. We have developed a cardiac organ-chip using pluripotent stem cells enhance cell maturity model cardiotoxicity.
Wnt signaling is intrinsic to mouse embryonic stem cell self-renewal. Therefore, it surprising that reprogramming of somatic cells induced pluripotent (iPSCs) not strongly enhanced by signaling. Here, we demonstrate active inhibits the early stage iPSCs, whereas required and even stimulating during late stage. Mechanistically, this biphasic effect accompanied a change in requirement all four its transcriptional effectors: T factor 1 (Tcf1), Lef1, Tcf3, Tcf4. For example, Tcf3 Tcf4 are...
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...
The origin, composition, distribution, and function of cells in the human intervertebral disc (IVD) have not been fully understood. Here, cell atlases both neonatal adult IVDs generated further assessed by gene ontology pathway enrichment, pseudo-time trajectory, histology, immunofluorescence. Comparison revealed presence two subpopulations notochordal (NCs) their associated markers IVDs. Developmental trajectories predicted 7 different states that describe developmental process from to IVD...
Human induced pluripotent stem cells (iPSCs) are a renewable cell source that can be differentiated into neural progenitor (iNPCs) and transduced with glial line-derived neurotrophic factor (iNPC-GDNFs). The goal of the current study is to characterize iNPC-GDNFs test their therapeutic potential safety. Single-nuclei RNA-seq show express NPC markers. delivered subretinal space Royal College Surgeons rodent model retinal degeneration preserve photoreceptors visual function. Additionally,...
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....
Abstract Introduction The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are hexanucleotide repeats in chromosome 9 open reading frame 72 ( C9orf72) . These produce dipeptide repeat proteins with poly(PR) being the toxic one. Methods We performed a kinome‐wide CRISPR/Cas9 knock‐out screen human induced pluripotent stem cell (iPSC) ‐derived cortical neurons to identify modifiers toxicity, validated role candidate using vitro, vivo, ex‐vivo...
Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease characterized by dysfunction and loss of upper lower motor neurons (MN). Despite several studies identifying drastic alterations affecting synaptic composition functionality in different experimental models, the specific contribution impaired activity to processes observed ALS-related MN remains controversial. In particular, contrasting lines evidence have shown both hyper- as well hypoexcitability driving...