A5049621870- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Inflammasome and immune disorders
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neural Engineering
- Endoplasmic Reticulum Stress and Disease
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Cellular transport and secretion
- Tryptophan and brain disorders
- Multiple Sclerosis Research Studies
- Extracellular vesicles in disease
- Lipid Membrane Structure and Behavior
- Epigenetics and DNA Methylation
- 3D Printing in Biomedical Research
- interferon and immune responses
- Protein Hydrolysis and Bioactive Peptides
- Bone and Dental Protein Studies
Columbia University
2023-2024
Columbia University Irving Medical Center
2022-2024
The Neurological Institute
2024
Institute on Aging
2023
Rush University Medical Center
2023
Karolinska Institutet
2017-2019
Lund University
2015-2018
Abstract Microglia and neuroinflammation play an important role in the development progression of Alzheimer’s disease (AD). Inositol polyphosphate-5-phosphatase D ( INPP5D/SHIP1 ) is a myeloid-expressed gene genetically-associated with AD. Through unbiased analyses RNA protein profiles INPP5D-disrupted iPSC-derived human microglia, we find that reduction INPP5D activity associated molecular consistent disrupted autophagy inflammasome activation. These findings are validated through targeted...
Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition hyperphosphorylated tau in patient brains. However, mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses FTD brains with a stem cell culture and transplantation model FTD. We identified disease phenotypes neurons carrying MAPT-N279K mutation, which were related oxidative stress, phosphorylation, neuroinflammation upregulation...
We generated human iPS derived neural stem cells and differentiated from healthy control individuals an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion. investigated the expression of during induction differentiation observed a pivotal role for early neuronal differentiation. Single cell RNA-seq pinpointed deletion shifting towards radial glia-like identity revealed higher proportion astroglia. Furthermore, were identified as immature by single analysis,...
Abstract We used single‐cell RNA sequencing (seq) on several human induced pluripotent stem (iPS) cell‐derived neural cell (NSC) lines and one fetal brain‐derived NSC line to study inherent type heterogeneity at proliferating stage uncovered predisposed presence of neurogenic gliogenic progenitors. observed in progenitors that differed between the iPS fetal‐derived line, we also differences spontaneous differentiation potential for inhibitory excitatory neurons line. In addition, using a...
Abstract A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ‘’protein-centric” view increasingly challenged by evidence for the involvement specialized membrane domains transduction. Here, we propose perturbation may serve as an alternative mechanism to a conserved cell-death program cancer cells. emerges from extraordinary manner HAMLET (Human Alpha-lactalbumin Made...
Abstract Alzheimer’s disease (AD) is the most common cause of dementia, and mechanisms are still not fully understood. Here, we explored pathological changes in human induced pluripotent stem cell (iPSC)-derived neurons carrying familial AD APP V717I mutation after injection into mouse forebrain. mutant iPSCs isogenic controls were differentiated revealing enhanced Aβ 42 production, elevated phospho-tau, impaired neurite outgrowth neurons. Two months transplantation, control neural cells...
Microglia and neuroinflammation are implicated in the development progression of Alzheimer's disease (AD). To better understand microglia-mediated processes AD, we studied function INPP5D/SHIP1, a gene linked to AD through GWAS. Immunostaining single nucleus RNA sequencing confirmed that INPP5D expression adult human brain is largely restricted microglia. Examination prefrontal cortex across large cohort revealed reduced full length protein levels patient brains compared cognitively normal...
Human neurodegenerative disorders affect specific types of cortical neurons. Efficient protocols for the generation such neurons cell replacement, disease modeling and drug screening are highly warranted. Current methods production from human embryonic stem (ES) cells often time-consuming inefficient, functional properties generated have been incompletely characterized. Here we used transcription factor (TF) programming with aim to induce rapid differentiation ES layer-specific (hES-iNs)....
Recent investigations of cell type changes in Multiple Sclerosis (MS) using single-cell profiling methods have focused on active lesional and peri-lesional brain tissue, implicated a number peripheral central nervous system types. However, an important question is the extent to which so-called "normal-appearing" non-lesional tissue individuals with MS accumulate over lifespan. Here, we compared post-mortem from donors pathological or clinical diagnosis Religious Orders Study Rush Memory...
Abstract Background Alzheimer’s disease (AD) and AD‐related dementias (ADRD) are fatal neurodegenerative diseases that impair the cognitive function of more than 40 million people worldwide without effective treatments. Despite high prevalence AD ADRD, molecular mechanisms neurodegeneration only partially understood. Emerging evidence supports physiological relevance using induced pluripotent stem cell (iPSC) to model related dementias. This study is set determine neuron‐autonomous changes...