Evan Y. Snyder
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View article: The cryo-EM-delineated mechanism underlying mimicry of CXCR4 agonism enables widespread stem cell neuroprotection in a mouse model of ALS
The cryo-EM-delineated mechanism underlying mimicry of CXCR4 agonism enables widespread stem cell neuroprotection in a mouse model of ALS Open
G-protein coupled receptors (GPCRs) are transmembrane proteins that mediate a range of signaling functions and, therefore, offer targets for a number of therapeutic interventions. Chemokine receptor CXCR4, a GPCR, plays versatile roles in …
View article: Modeling patient-specific adenocarcinoma as spheroids enhances the authenticity of cancer hallmarks and therapeutic susceptibility
Modeling patient-specific adenocarcinoma as spheroids enhances the authenticity of cancer hallmarks and therapeutic susceptibility Open
Introduction: To help understand and develop treatments for cancer, it is important to have patient-specific, reliable and physiologically-relevant human culture models. Cells from solid tumors have traditionally been grown in 2-dimensiona…
View article: Modeling the Aging Human Lung: Generation of a Senescent Human Lung Organoid Culture System
Modeling the Aging Human Lung: Generation of a Senescent Human Lung Organoid Culture System Open
Introduction The aging lung enters into a state of irreversible cellular growth arrest characterized by senescence. While senescence is beneficial in preventing oncogenic cell proliferation, it becomes detrimental when persistent, promotin…
View article: A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response
A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response Open
The prevalence of “long COVID” is just one of the conundrums highlighting how little we know about the lung’s response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We use…
View article: Protocol to optimize the Rice-Vannucci rat pup model of perinatal asphyxia to ensure predictable hypoxic-ischemic cerebral lesions
Protocol to optimize the Rice-Vannucci rat pup model of perinatal asphyxia to ensure predictable hypoxic-ischemic cerebral lesions Open
The Rice-Vannucci model in rodent pups is subject to substantial loss of animals, result inconsistency, and high lab-to-lab variability in extent and composition of induced injury. This protocol allows for highly predictable and reproducib…
View article: The effects of cell-cell orientation in modeling the hallmarks of lung cancer in vitro
The effects of cell-cell orientation in modeling the hallmarks of lung cancer in vitro Open
To better understand and develop treatments for lung cancer, it is important to have reliable and physiologically relevant culture models. Traditional methods of growing lung cancer cells in two- dimensional (2D) monolayers have limitation…
View article: The lung employs an intrinsic surfactant-mediated inflammatory response for viral defense
The lung employs an intrinsic surfactant-mediated inflammatory response for viral defense Open
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) causes an acute respiratory distress syndrome (ARDS) that resembles surfactant deficient RDS. Using a novel multi-cell type, human induced pluripotent stem cell (hiPSC)-derived l…
View article: Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia
Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia Open
Significance There are no biomarkers for schizophrenia (SCZ), a disorder of dysfunctional neural networks. We demonstrate that a master regulator of cytoskeleton (“CRMP2”) and, hence, neural circuitry, may form the basis for such a biomark…
View article: The Developmental & Molecular Requirements for Ensuring that Human Pluripotent Stem Cell-Derived Hair Follicle Bulge Stem Cells Have Acquired Competence for Hair Follicle Generation Following Transplantation
The Developmental & Molecular Requirements for Ensuring that Human Pluripotent Stem Cell-Derived Hair Follicle Bulge Stem Cells Have Acquired Competence for Hair Follicle Generation Following Transplantation Open
When using human induced pluripotent stem cells (hiPSCs) to achieve hair follicle (HF) replacement, we found it best to emulate the earliest fundamental developmental processes of gastrulation, ectodermal lineage commitment, and dermogenes…
View article: Chemical mutagenesis of a GPCR ligand: Detoxifying “inflammo-attraction” to direct therapeutic stem cell migration
Chemical mutagenesis of a GPCR ligand: Detoxifying “inflammo-attraction” to direct therapeutic stem cell migration Open
Significance While inflammatory chemokines, constitutively produced by pathologic regions, are pivotal for attracting reparative stem cells, one would certainly not want to further “inflame” a diseased brain by instilling such molecules. E…
View article: Human Neural Stem Cells Survive Long Term in the Midbrain of Dopamine-Depleted Monkeys After GDNF Overexpression and Project Neurites Toward an Appropriate Target
Human Neural Stem Cells Survive Long Term in the Midbrain of Dopamine-Depleted Monkeys After GDNF Overexpression and Project Neurites Toward an Appropriate Target Open
Transplanted multipotent human fetal neural stem cells (hfNSCs) significantly improved the function of parkinsonian monkeys in a prior study primarily by neuroprotection, with only 3%–5% of cells expressing a dopamine (DA) phenotype. In th…
View article: Countermeasures for Preventing and Treating Opioid Overdose
Countermeasures for Preventing and Treating Opioid Overdose Open
The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Because of its pharmacokinetic and pharmacodynamic properties, naloxone …
View article: Nna1 gene deficiency triggers Purkinje neuron death by tubulin hyperglutamylation and ER dysfunction
Nna1 gene deficiency triggers Purkinje neuron death by tubulin hyperglutamylation and ER dysfunction Open
Posttranslational glutamylation/deglutamylation balance in tubulins influences dendritic maturation and neuronal survival of cerebellar Purkinje neurons (PNs). PNs and some additional neuronal types degenerate in several spontaneous, indep…
View article: Generation of Complete Multi−Cell Type Lung Organoids From Human Embryonic and Patient‐Specific Induced Pluripotent Stem Cells for Infectious Disease Modeling and Therapeutics Validation
Generation of Complete Multi−Cell Type Lung Organoids From Human Embryonic and Patient‐Specific Induced Pluripotent Stem Cells for Infectious Disease Modeling and Therapeutics Validation Open
The normal development of the pulmonary system is critical to transitioning from placental‐dependent fetal life to alveolar‐dependent newborn life. Human lung development and disease have been difficult to study due to the lack of an in vi…
View article: A Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury
A Biomarker for Predicting Responsiveness to Stem Cell Therapy Based on Mechanism-of-Action: Evidence from Cerebral Injury Open
To date, no stem cell therapy has been directed to specific recipients-and, conversely, withheld from others-based on a clinical or molecular profile congruent with that cell's therapeutic mechanism-of-action (MOA) for that condition. We a…
View article: The Evolution of Stem Cells, Disease Modeling, and Drug Discovery for Neurological Disorders
The Evolution of Stem Cells, Disease Modeling, and Drug Discovery for Neurological Disorders Open
Human neurological disorders are among the most challenging areas of translational research. The difficulty of acquiring human neural samples or specific representative animal models has necessitated a multifaceted approach to understandin…
View article: Driving Neuronal Differentiation through Reversal of an ERK1/2-miR-124-SOX9 Axis Abrogates Glioblastoma Aggressiveness
Driving Neuronal Differentiation through Reversal of an ERK1/2-miR-124-SOX9 Axis Abrogates Glioblastoma Aggressiveness Open
Identifying cellular programs that drive cancers to be stem-like and treatment resistant is critical to improving outcomes in patients. Here, we demonstrate that constitutive extracellular signal-regulated kinase 1/2 (ERK1/2) activation su…
View article: Novel Bivalent and D-Peptide Ligands of CXCR4 Mobilize Hematopoietic Progenitor Cells to the Blood in C3H/HeJ Mice
Novel Bivalent and D-Peptide Ligands of CXCR4 Mobilize Hematopoietic Progenitor Cells to the Blood in C3H/HeJ Mice Open
The interaction of SDF-1α (also known as CXCL12) with the CXCR4 receptor plays a critical role in the retention of hematopoietic stem cells (HSCs) in bone marrow. The viral macrophage inflammatory protein-II (vMIP-II), a human herpesvirus-…
View article: Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory set-point for a cytoskeletal modulator in bipolar pathogenesis
Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory set-point for a cytoskeletal modulator in bipolar pathogenesis Open
Significance One-third of bipolar disorder (BPD) patients are lithium-responsive (LiR) for unknown reasons. Were lithium’s target to be identified, then BPD’s pathogenesis might be unraveled. We identified and mapped the “lithium-response …
View article: Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling
Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling Open
Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical …
View article: Neural Stem Cells Derived from Human Parthenogenetic Stem Cells Engraft and Promote Recovery in a Nonhuman Primate Model of Parkinson's Disease
Neural Stem Cells Derived from Human Parthenogenetic Stem Cells Engraft and Promote Recovery in a Nonhuman Primate Model of Parkinson's Disease Open
Cell therapy has attracted considerable interest as a promising therapeutic alternative for patients with Parkinson's disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clini…