A5048339270- Extracellular vesicles in disease
- HER2/EGFR in Cancer Research
- Alzheimer's disease research and treatments
- Cancer Cells and Metastasis
- Neurogenesis and neuroplasticity mechanisms
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
- Nerve injury and regeneration
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Pregnancy and preeclampsia studies
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Prion Diseases and Protein Misfolding
- Advanced Biosensing Techniques and Applications
- Protein Degradation and Inhibitors
- Glioma Diagnosis and Treatment
- Birth, Development, and Health
- Nicotinic Acetylcholine Receptors Study
- Amyotrophic Lateral Sclerosis Research
- Reproductive System and Pregnancy
- Dementia and Cognitive Impairment Research
- Neurological diseases and metabolism
- Circular RNAs in diseases
University of California, San Diego
2016-2025
LAC+USC Medical Center
2023
University of Southern California
2023
University of California, Irvine
2023
Cedars-Sinai Medical Center
2023
Illinois College
2023
Tripler Army Medical Center
2023
Universidad Católica Santo Domingo
2022
VA San Diego Healthcare System
2021
La Jolla Alcohol Research
2019
Expanded hexanucleotide repeats in the chromosome 9 open reading frame 72 (C9orf72) gene are most common genetic cause of ALS and frontotemporal degeneration (FTD). Here, we identify nuclear RNA foci containing expansion (GGGGCC) patient cells, including white blood fibroblasts, glia, multiple neuronal cell types (spinal motor, cortical, hippocampal, cerebellar neurons). not present sporadic ALS, familial ALS/FTD caused by other mutations (SOD1, TDP-43, or tau), Parkinson disease,...
High fat diets and obesity pose serious health problems, such as type II diabetes cardiovascular disease. Impaired cognitive function is also associated with high intake. In this study, we show that just 4 weeks of feeding a diet rich in ad libitum decreased hippocampal neurogenesis male, but not female, rats. There was no obesity, male rats fed exhibited elevated serum corticosterone levels compared those standard rat chow. These data indicate dietary intake can disrupt neurogenesis,...
ABSTRACT An increasing body of evidence points to significant spatio-temporal differences in early placental development between mouse and human, but a detailed comparison placentae these two species is missing. We set out compare from both across gestation, with focus on trophoblast progenitor markers. found that CDX2 ELF5, not EOMES, are expressed post-implantation subpopulations species. Genome-wide expression profiling human revealed clusters genes distinct co-expression patterns...
Abstract Cancer-secreted, extracellular vesicle (EV)–encapsulated miRNAs enable cancer cells to communicate with each other and noncancerous in tumor pathogenesis response therapies. Here, we show that treatment a sublethal dose of chemotherapeutic agents induces breast secrete EV the capacity stimulate stem-like cell (CSC) phenotype, rendering resistance therapy. Chemotherapy induced multiple miRNAs, including miR-9-5p, miR-195-5p, miR-203a-3p, which simultaneously targeted transcription...
Phosphorylation of α-synuclein at the serine-129 site (α-syn Ser129P) is an established pathologic hallmark synucleinopathies and a therapeutic target. In physiologic states, only fraction α-syn phosphorylated this site, most studies have focused on roles post-translational modification. We found that unlike wild-type (WT) α-syn, which widely expressed throughout brain, overall pattern Ser129P restricted, suggesting intrinsic regulation. Surprisingly, preventing blocked activity-dependent...
Breast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with metastases display poor prognosis survival due lack of effective therapeutics treatment strategies. Recent work intravital microscopy preclinical animal models indicates metastatic colonize specifically in close contact existing vasculature. However, it is not known how vascular niche promotes microtumor formation. Here, we investigate role connexins...
Significance Human pluripotent stem cells (hPSCs) continue to be underappreciated as a model for studying trophoblast differentiation. In this study, we provide reproducible, two-step protocol by which hPSCs can differentiated into bipotential cytotrophoblast (CTB) stem-like and subsequently functional, terminally trophoblasts. addition, evidence that the response of hPSC-derived CTBs low oxygen is similar primary CTBs. Finally, using trisomy 21-affected hPSCs, show, first time our...
The placenta is a transient organ that necessary for proper fetal development. Its main functional component the trophoblast, which derived from extra-embryonic ectoderm. Little known about early trophoblast differentiation in human embryo, owing to lack of vitro model system. Human embryonic stem cells (hESCs) differentiate into following BMP4 treatment presence feeder-conditioned media; however, this has not been widely accepted, part proof progenitor population. We have previously shown...
Chronic pancreatitis is an inflammatory disease that causes progressive destruction of pancreatic acinar cells and, ultimately, loss function. We investigated the role IκB kinase α (IKKα) in homeostasis. Pancreas-specific ablation IKKα (Ikkα(Δpan)) caused spontaneous and cell vacuolization death, interstitial fibrosis, inflammation, circulatory release enzymes, clinical signs resembling those human chronic pancreatitis. Loss defective autophagic protein degradation, leading to accumulation...
Human cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect a sensory network in vivo has yet be demonstrated. Here, we combine transparent microelectrode arrays two-photon imaging for longitudinal, multimodal monitoring of human transplanted into the retrosplenial cortex adult mice. Two-photon shows vascularization organoid. Visual stimuli evoke...
Trophoblast stem cells (TSCs) have recently been derived from human embryos and early-first-trimester placenta; however, aside ethical challenges, the unknown disease potential of these limits their scientific utility. We previously established a bone morphogetic protein 4 (BMP4)-based two-step protocol for differentiation primed pluripotent (hPSCs) into functional trophoblasts; those trophoblasts could not be maintained in self-renewing TSC-like state. Here, we use first step this protocol,...
Alzheimer's disease (AD) is the most prevalent cause of dementia; microglia have been implicated in AD pathogenesis, but their role still matter debate. Our study showed that single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation rescued phenotype 5xFAD mice may prevent activation. Indeed, complete prevention memory loss neurocognitive impairment decrease β-amyloid plaques hippocampus cortex were observed WT HSPC-transplanted compared with untreated...
In this study we examined the developmental roles of acetylcholine (ACh) by establishing and analyzing mice lacking choline acetyltransferase (ChAT), biosynthetic enzyme for ACh. As predicted, ChAT-deficient embryos lack both spontaneous nerve-evoked postsynaptic potentials in muscle die at birth. mutant embryos, abnormally increased nerve branching occurs on contact with muscle, hyperinnervation continues throughout subsequent prenatal development. Postsynaptically, ACh receptor clusters...
Recruitment of monocytes into sites inflammation is essential in the immune response. In cancer, recruited promote invasion, metastasis, and possibly angiogenesis. LDL receptor-related protein (LRP1) an endocytic cell-signaling receptor that regulates cell migration. this study, we isografted PanO2 pancreatic carcinoma cells mice which LRP1 was deleted myeloid lineage cells. orthotopic subcutaneous tumors significantly increased these mice, compared with control mice. LRP1-deficient bone...
The available evidence suggests that the lethality of glioblastoma is driven by small subpopulations cells self-renew and exhibit tumorigenicity. It remains unclear whether tumorigenicity exists as a static property few or dynamically acquired property. We used tumor-sphere xenograft formation assays for examined subclones isolated from established primary lines. Our results indicate largely deterministic, yet can be spontaneously at low frequencies. Further, these dynamic transitions are...
Mutations in TDP-43 cause amyotrophic lateral sclerosis (ALS), a fatal paralytic disease characterized by degeneration and premature death of motor neurons. The contribution mutant TDP-43-mediated damage within neurons was evaluated using mice expressing conditional allele an ALS-causing (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43. TDP-43Q331K develop age- mutant-dependent deficits from Cre-recombinase-mediated excision gene is shown to delay...
Choline acetyltransferase (ChAT), the enzyme that synthesizes neurotransmitter acetylcholine (ACh), is thought to be present in kinetic excess cholinergic neurons. The rate-limiting factor ACh production provision of choline ChAT. Cholinergic neurons are relatively unique their expression transporter 1 (CHT1), which exhibits high-affinity for and catalyzes its uptake from extracellular space neuron. Multiple lines evidence indicate activity CHT1 a key determinant supply synthesis. We...