A5027351012- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- RNA Research and Splicing
- Tissue Engineering and Regenerative Medicine
- Genetic Neurodegenerative Diseases
- CAR-T cell therapy research
- Neuroscience and Neuropharmacology Research
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Amyotrophic Lateral Sclerosis Research
- RNA modifications and cancer
- Receptor Mechanisms and Signaling
- Congenital heart defects research
- RNA Interference and Gene Delivery
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Liver physiology and pathology
- Genetics and Neurodevelopmental Disorders
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Molecular Biology Techniques and Applications
- Neuropeptides and Animal Physiology
- Neurogenetic and Muscular Disorders Research
- Connexins and lens biology
St. Jude Children's Research Hospital
2006-2024
King's College London
2024
Rutgers, The State University of New Jersey
2010-2021
National Institute of Mental Health
2021
University of Alabama
2020
NIMH Repository and Genomics Resource
2020
National Institute of Neurological Disorders and Stroke
2020
National Institutes of Health
2020
Rutgers Sexual and Reproductive Health and Rights
2018-2019
Wake Forest University
2019
Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested in vivo relevance through genetic ablation animal models. To investigate the of lncRNAs various physiological conditions, we developed a collection 18 lncRNA knockout strains which locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes three mutant (Fendrr, Peril, Mdgt), latter two exhibiting incomplete penetrance growth...
Abstract DDX3X is a DEAD-box RNA helicase that has been implicated in multiple aspects of metabolism including translation initiation and the assembly stress granules (SGs). Recent genomic studies have reported recurrent mutations numerous tumors medulloblastoma (MB), but physiological impact these poorly understood. Here we show consistent feature MB-associated SG hyper-assembly concomitant impairment. We used CLIP-seq to obtain comprehensive assessment binding targets ribosome profiling...
Abstract Cell replacement therapy with human pluripotent stem cell-derived neurons has the potential to ameliorate neurodegenerative dysfunction and central nervous system injuries, but reprogrammed are dissociated spatially disorganized during transplantation, rendering poor cell survival, functionality engraftment in vivo . Here, we present design of three-dimensional (3D) microtopographic scaffolds, using tunable electrospun microfibrous polymeric substrates that promote situ neuronal...
Lentiviral vectors are increasingly utilized in cell and gene therapy applications because they efficiently transduce target cells such as hematopoietic stem T cells. Large-scale production of current Good Manufacturing Practices-grade lentiviral is limited the adherent, serum-dependent nature HEK293T used manufacturing process. To optimize large-scale clinical-grade vector production, we developed an improved scheme by adapting to grow suspension using commercially available chemically...
Heterozygous NRXN1 deletions constitute the most prevalent currently known single-gene mutation associated with schizophrenia, and additionally predispose to multiple other neurodevelopmental disorders. Engineered heterozygous impaired neurotransmitter release in human neurons, suggesting a synaptic pathophysiological mechanism. Utilizing this observation for drug discovery, however, requires confidence its robustness validity. Here, we describe multicenter effort test generality of pivotal...
Background MicroRNAs are required for maintenance of pluripotency as well differentiation, but since more microRNAs have been computationally predicted in genome than found, there likely to be undiscovered expressed early stem cell differentiation. Methodology/Principal Findings SOLiD ultra-deep sequencing identified >107 unique small RNAs from human embryonic cells (hESC) and neural-restricted precursors that were fit a model microRNA biogenesis predict 818 new genes. These genomic loci...
B7-H3 is actively being explored as an immunotherapy target for pediatric patients with solid tumors using monoclonal antibodies or T cells expressing chimeric antigen receptors (CARs). B7-H3-CARs containing a 41BB costimulatory domain are currently favored by several groups based on preclinical studies. In this study, we initially performed detailed analysis of different hinge/transmembrane (CD8α versus CD28) and CD28 domains (CD8α/CD28, CD8α/41BB, CD28/CD28, CD28/41BB). Only subtle...
Background— Differentiation of pluripotent human embryonic stem cells (hESCs) to the cardiac lineage represents a potentially unlimited source ventricular cardiomyocytes (VCMs), but hESC-VCMs are developmentally immature. Previous attempts profile primarily relied on transcriptomic approaches, global proteome has not been examined. Furthermore, most hESC-CM studies focus pathways important for differentiation, rather than regulatory mechanisms CM maturation. We hypothesized that gene...
Abstract Oxytocin (OT), a hormone recently identified in the heart, induces embryonic and cardiac somatic stem cells to differentiate into cardiomyocytes (CM), possibly through nitric oxide (NO). We verified this hypothesis using P19 Clone 6 derivatives expressing green fluorescent protein (GFP) reporter linked myosin light chain-2v promoter. OT treatment of these induced beating cell colonies that were fully inhibited by N,G-nitro-l-arginine-methyl-ester (l-NAME), an inhibitor NO synthases...
Substrates used to culture human embryonic stem cells (hESCs) are typically 2-dimensional (2-D) in nature, with limited ability recapitulate vivo-like 3-dimensional (3-D) microenvironments. We examined critical determinants of hESC self-renewal poly-d-lysine-pretreated synthetic polymer-based substrates variable microgeometries, including planar 2-D films, macroporous 3-D sponges, and microfibrous fiber mats. Completely scaffolds failed retain hESCs or support differentiation. However,...
Herpes simplex virus, type 1 (HSV-1) commonly produces lytic mucosal lesions. It invariably initiates latent infection in sensory ganglia enabling persistent, lifelong infection. Acute HSV-1 encephalitis is rare and definitive evidence of the brain lacking. However, exposure untraceable to has been repeatedly associated with impaired working memory executive functions, particularly among schizophrenia patients. Patterns gene expression changes were examined human induced pluripotent stem...
Abstract Recent advancements in the production of hepatocytes from human pluripotent stem cells (hPSC-Heps) afford tremendous possibilities for treatment patients with liver disease. Validated current good manufacturing practice (cGMP) lines are an essential prerequisite such applications but have only recently been established. Whether cGMP capable hepatic differentiation is not known. To address this knowledge gap, we examined proficiency three derived (two hiPSC and one hESC) to...
Importance Current Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) ( DSM-5 ) diagnoses substance use disorders rely on criterion count–based approaches, disregarding severity grading indexed by individual criteria. Objective To examine correlates alcohol disorder (AUD) across count-based groups (ie, mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative greater severity, evaluate whether within mild-to-moderate AUD differentiate...