A5087749670- Neuroscience and Neural Engineering
- Planarian Biology and Electrostimulation
- RNA Interference and Gene Delivery
- 3D Printing in Biomedical Research
- Virus-based gene therapy research
- RNA regulation and disease
- Electromagnetic Fields and Biological Effects
- Lysosomal Storage Disorders Research
- Neurogenetic and Muscular Disorders Research
- Plant and Biological Electrophysiology Studies
- Magnetic and Electromagnetic Effects
- Microfluidic and Bio-sensing Technologies
- Genetic Neurodegenerative Diseases
- Cerebrospinal fluid and hydrocephalus
- Biofield Effects and Biophysics
- Brain Metastases and Treatment
- Advanced biosensing and bioanalysis techniques
- Glioma Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Microbial Inactivation Methods
- Alcoholism and Thiamine Deficiency
- Diabetes Management and Research
- Neurogenesis and neuroplasticity mechanisms
- Neurological diseases and metabolism
- Pancreatic function and diabetes
University of Massachusetts Chan Medical School
2019-2025
University of Cincinnati
2012-2015
Regulation of cell function by a non-thermal, physiological-level electromagnetic field has potential for vascular tissue healing therapies and advancing hybrid bioelectronic technology. We have recently demonstrated that physiological electric (EF) applied wirelessly can regulate intracellular signalling in frequency-dependent manner. However, the mechanism such regulation is not well understood. Here, we present systematic numerical study cell-field interaction following exposure to...
Global gene delivery to the CNS has therapeutic importance for treatment of neurological disorders that affect entire CNS. Due direct contact with CNS, cerebrospinal fluid (CSF) is an attractive route delivery. A safe and effective achieve global distribution in needed, administration genes through cisterna magna (CM) via a suboccipital puncture results broad brain spinal cord. However, translation this technique clinical practice challenging due risk serious potentially fatal complications...
Classic maple syrup urine disease (MSUD) results from biallelic mutations in genes that encode the branched-chain α-ketoacid dehydrogenase E1 α ( BCKDHA ), β BCKDHB or dihydrolipoamide transacylase DBT ) subunits, which interact to form mitochondrial BCKDH complex decarboxylates ketoacid derivatives of leucine, isoleucine, and valine. MSUD is an inborn error metabolism characterized by recurrent life-threatening neurologic crises progressive brain injury can only be managed with exacting...
Low-amplitude electric field (EF) is an important component of wound-healing response and can promote vascular tissue repair; however, the mechanisms action on endothelium remain unclear. We hypothesized that physiological amplitude EF regulates angiogenic microvascular endothelial cells via activation mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. A custom set-up allowed non-thermal application high (7.5 GHz) low (60 Hz) frequency. Cell responses...
The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff (SD), are fatal lysosomal storage disorders caused by mutations in the HEXA HEXB genes, respectively. These cause dysfunction of enzyme β-N-acetylhexosaminidase A (HexA) accumulation ganglioside (GM2) with ensuing neurodegeneration, death 5 years age. Until recently, most successful therapy was achieved intracranial co-delivery monocistronic adeno-associated viral (AAV) vectors encoding Hex alpha beta-subunits animal models SD....
Diabetic cardiomyopathy (DCM) is a diabetic complication, which results in myocardial dysfunction independent of other etiological factors. Abnormal intracellular calcium ([Ca2+]i) homeostasis has been implicated DCM and may precede clinical manifestation. Studies cardiomyocytes have shown that diabetes impaired [Ca2+]i due to altered sarcoplasmic reticulum Ca2+ ATPase (SERCA) sodium-calcium exchanger (NCX) activity. Importantly, also be involved diabetes-associated endothelial dysfunction,...
siRNAs comprise a class of drugs that can be programmed to silence any target gene. Chemical engineering efforts resulted in development divalent (di-siRNAs), which support robust and long-term efficacy rodent nonhuman primate brains upon direct cerebrospinal fluid (CSF) administration. Oligonucleotide distribution the CNS is nonuniform, limiting clinical applications. The contribution CSF infusion placement dosing regimen on relative accumulation, specifically context large animals, not...
Neurological disorders pose a challenge for targeted therapy due to restricted access of therapeutic agents the central nervous system (CNS). Current methods are limited by procedure-related risks, invasiveness, and insufficient CNS biodistribution. A novel percutaneous transvenous technology, currently in clinical trials communicating hydrocephalus, offers minimally invasive approach providing endovascular cerebrospinal fluid-filled cerebellopontine angle (CPA) cistern. We hypothesized that...
Huntington's disease (HD) is a fatal neurodegenerative autosomal dominant disorder with prevalence of 1 : 20000 that has no effective treatment to date. Translatability candidate therapeutics could be enhanced by additional testing in large animal models because similarities brain anatomy, size, and immunophysiology. These features enable realistic pre-clinical studies biodistribution, efficacy, toxicity.Here we non-invasively characterized alterations white matter microstructure,...
Transformative results of adeno-associated virus (AAV) gene therapy in patients with spinal muscular atrophy and Leber's congenital amaurosis led to approval the first two AAV products United States treat these diseases. These extraordinary a dramatic increase number type gene-therapy programs. However, field lacks non-invasive means assess levels duration therapeutic protein function patients. Here, we describe new magnetic resonance imaging (MRI) technology for real-time reporting living...
Diabetes-induced cardiomyopathy is characterized by cardiac remodeling, fibrosis, and endothelial dysfunction, with no treatment options currently available. Hyperglycemic memory cells may play the key role in microvascular complications diabetes, providing a potential target for therapeutic approaches. This study tested hypothesis that proangiogenic environment can augment diabetes-induced deficiencies cell angiogenic biomechanical responses. Endothelial responses were quantified two models...
Thalamic infusion of adeno-associated viral (AAV) vectors has been shown to have therapeutic effects in neuronopathic lysosomal storage diseases. Preclinical studies sheep model Tay-Sachs disease demonstrated that bilateral thalamic injections AAV gene therapy are required for maximal benefit. Translation injection patients carries risks (1) it never done humans, and (2) dosing scale-up based on brain weight from animals humans requires larger volumes. To increase the safety margin this...
Abstract Early pro‐inflammatory signaling in the endocrine pancreas involves activation of NF‐κB, which is believed to be important for determining ultimate fate β‐cells and hence progression type 1 diabetes (T1D). Thus, early non‐invasive detection NF‐κB pancreatic islets may serve as a potential strategy monitoring changes cells eventually leading T1D. We investigated feasibility optical imaging transcription factor induced by low‐dose streptozocin (LD‐STZ) treatment immunocompetent SKH1...
Abstract BACKGROUND Appropriate drug distribution is needed for effective treatment of brain metastases and leptomeningeal disease. Lack proper bioavailability in the CNS contributes to poor outcome these patients. EnClear Therapies has developed a device delivering intrathecal therapeutics utilizing dynamic control CSF flow through an external pump. Herein, we look at delivery methotrexate with EnClear’s system its impact concentration tissue sheep non-human primates. METHODS utilizes two...
Synaptic changes occur early in patients with Huntington's disease (HD) and mouse models of HD. An analysis synaptic HD transgenic sheep (OVT73) is fitting since they have been shown to some phenotypes. They also larger brains, longer lifespan, greater motor cognitive capacities more aligned humans, can provide abundant biofluids for vivo monitoring therapeutic interventions.The objective this study was determine if there were differences between 5- 10-year-old OVT73 wild-type (WT) levels...
Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome pre-clinical studies. (1) They carry a well-established dose-related acute neurotoxicity at time administration. (2) Repeated administration into cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated prevent toxicity, but sensitive and quantitative way...