- Neurogenesis and neuroplasticity mechanisms
- Alzheimer's disease research and treatments
- Pluripotent Stem Cells Research
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Retinal Development and Disorders
- Tissue Engineering and Regenerative Medicine
- Retinal Diseases and Treatments
- Mesenchymal stem cell research
- Neurological Disease Mechanisms and Treatments
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Cerebrospinal fluid and hydrocephalus
- Neurogenetic and Muscular Disorders Research
- Genetics, Aging, and Longevity in Model Organisms
- Cholinesterase and Neurodegenerative Diseases
- Growth Hormone and Insulin-like Growth Factors
- Medicinal Plants and Neuroprotection
- Protease and Inhibitor Mechanisms
- Signaling Pathways in Disease
- Muscle Physiology and Disorders
- Coronary Interventions and Diagnostics
- RNA Interference and Gene Delivery
- Metabolism, Diabetes, and Cancer
University of Michigan
2014-2023
Ollscoil na Gaillimhe – University of Galway
2006-2013
University Hospital Galway
2010-2013
Stem cell transplantation offers a potentially transformative approach to treating neurodegenerative disorders. The safety of cellular therapies is established in multiple clinical trials, including our own amyotrophic lateral sclerosis. To initiate similar trials Alzheimer's disease, efficacious lines must be identified. Here, we completed preclinical proof-of-concept study the APP/PS1 murine model disease. Human neural stem targeted fimbria fornix significantly improved cognition two...
Abstract Introduction A combination of gene and cell therapies has the potential to significantly enhance therapeutic value mesenchymal stem cells (MSCs). The development efficient delivery methods is essential if MSCs are be benefit using such an approach. Achieving high levels transgene expression for required period time, without adversely affecting viability differentiation capacity, crucial. In present study, we investigate lentiviral vector-mediated genetic modification rat bone-marrow...
Mesenchymal stem cell (MSC) therapy offers the potential to promote recovery after myocardial infarction (MI). However, therapeutic efficacy may be limited by poor survival and retention of transplanted cells. A combination gene has capacity prevent donor death augment reparative regenerative effects transfer. The present study investigates effect exogenous heat shock protein 27 (Hsp27) expression in MSCs an vitro model ischemia vivo rat MI aims determine if this could enhance benefit...
Abstract Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder and a leading cause of dementia. Current treatment fails to modify underlying pathologies very little progress has been made develop effective drug treatments. Cellular therapies impact by multiple mechanisms, providing increased efficacy compared with traditional single-target approaches. In amyotrophic lateral sclerosis, we have shown that transplanted spinal neural stem cells (NSCs) integrate...
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in motor neuron (MN) loss. There are currently no effective therapies; however, cellular therapies using neural progenitor cells protect MNs and attenuate disease progression G93A-SOD1 ALS rats. Recently, we completed phase I clinical trial examining intraspinal human spinal stem cell (HSSC) transplantation patients which demonstrated our approach was safe feasible, supporting the II progress. In...
Following spinal cord injury, a highly inhibitory environment for axonal regeneration develops. One of the main sources this inhibition is glial scar that formed after injury by reactive astrocytes. The mainly result chondroitin sulphate proteoglycans (CSPGs). NG2, [corrected] one CSPGs, up-regulated following injury.Small interfering RNA (siRNA) was designed to target NG2 and short hairpin (shRNA) cloned into lentiviral vector (LV). neurotrophic factor neurotrophin-3 (NT-3) promotes growth...
The hippocampus has been the target of stem cell transplantations in preclinical studies focused on Alzheimer's disease, with results showing improvements histological and behavioral outcomes. corpus callosum is another structure that affected early disease. Therefore, we hypothesize this a novel for human neural transplantation transgenic disease mouse models. This study demonstrates feasibility targeting identifies an effective immunosuppression regimen transplanted survival. These support...
Introduction Stem cells are a promising therapeutic in Alzheimer’s disease (AD) given the complex pathophysiologic pathways involved. However, mechanisms of stem remain unclear. Here, we used spatial transcriptomics to elucidate human neural (hNSCs) an animal model AD. Methods hNSCs were transplanted into fimbria fornix hippocampus using 5XFAD mouse model. Spatial memory was assessed by Morris water maze. Amyloid plaque burden quantified. performed and differentially expressed genes (DEGs)...
As the field of stem cell therapy advances, it is important to develop reliable methods overcome host immune responses in animal models. This ensures survival transplanted human grafts and enables predictive efficacy testing. Immunosuppressive drugs derived from clinical protocols are frequently used but often inconsistent associated with toxic side effects. Here, using a molecular imaging approach, we show that immunosuppression targeting costimulatory molecules CD4 CD40L robust xenografts...
<b><i>Background:</i></b> Almost all patients with amyotrophic lateral sclerosis (ALS) develop bulbar symptoms; therefore, it is important to have valid animal models that accurately reflect these features. While the SOD1-G93A rat extensively used as an ALS model, symptoms in this model are not well characterized. <b><i>Objective:</i></b> In present study, we aimed better characterize dysfunction terms of histology determine whether a useful...
Abstract Stem cell transplantation therapies are currently under investigation for central nervous system disorders. Although preclinical models show benefit, clinical translation is somewhat limited by the absence of reliable noninvasive methods to confirm targeting and monitor transplanted cells in vivo. Here, we assess a novel magnetic resonance imaging (MRI) contrast agent derived from magnetotactic bacteria, magneto-endosymbionts (MEs), as translatable methodology vivo tracking stem...
Stem cells are a promising therapeutic in Alzheimer's disease (AD) given the complex pathophysiologic pathways involved. However, mechanisms of stem remain unclear. Here, we used spatial transcriptomics to elucidate human neural (hNSCs) an animal model AD.
Age related macular degeneration (AMD) is a progressive degenerative disorder that affects the retina, retinal pigments and choriocapillaries of eye. Oxidative stress has been implicated in AMD through production reactive oxygen species (ROS) pigment epithelium (RPE), which provides structural nutritional support to retina. Blue light exposure, elevated tension high cellular lipid content contribute oxidative RPE.
Abstract Background Many pathways are implicated in pathogenesis of Alzheimer’s disease (AD). Stem cells a promising strategy to simultaneously correct multiple pathways; however, therapeutic mechanisms stem not well described. Here, we used spatial transcriptomics quantitate gene expression following intracranial transplantation human neural (hNSCs) mouse model AD. Method The 5XFAD was utilized. An hNSC cell line (HK532‐IGF1, Palisade Bio) transplanted into fimbria fornix the hippocampus (6...