A5084968847- Receptor Mechanisms and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Cytokine Signaling Pathways and Interactions
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- RNA Research and Splicing
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Immunotherapy and Immune Responses
- Nanoparticles: synthesis and applications
- Trace Elements in Health
- Parasites and Host Interactions
- Aquaculture disease management and microbiota
- Diabetes Management and Research
- Genetic Neurodegenerative Diseases
- Cell death mechanisms and regulation
- Renin-Angiotensin System Studies
- Nuclear Receptors and Signaling
- Nitric Oxide and Endothelin Effects
- Multiple Sclerosis Research Studies
- Mitochondrial Function and Pathology
- Neurological diseases and metabolism
- Complement system in diseases
- Invertebrate Immune Response Mechanisms
- Natural product bioactivities and synthesis
Drexel University
2015-2024
Institute for Molecular Medicine
2020
Cabrini University
2011
Multiple sclerosis (MS) is a debilitating chronic inflammatory disease of the nervous system that affects approximately 2.3 million individuals worldwide, with higher prevalence in females, and strong genetic component. While over 200 MS susceptibility loci have been identified GWAS, underlying mechanisms whereby they contribute to remains ill-defined. Forward genetics approaches using conventional laboratory mouse strains are useful identifying functionally dissecting genes controlling...
Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci encode HLA-DR -DQ. Genetic heterogeneity linkage disequilibrium in highly polymorphic HLA region confound attempts to identify additional susceptibility loci. To minimize heterogeneity, patients (N = 365) control subjects 668) homozygous for HLA-DR3 high-risk haplotype were selected from large studies examined new using molecular...
Biased agonists of G-protein-coupled receptors (GPCRs) have emerged as promising selective modulators signaling pathways by offering therapeutic advantages over unbiased to minimize side effects. The dopamine D3 receptor (D3R), a pivotal GPCR in the central nervous system, has gained significant attention target for neurological diseases, including Parkinson’s disease (PD), addiction, psychosis, depression, and anxiety. We recently designed tested SK609, G-protein biased D3R agonist,...
Glutamate excitotoxicity is causal in striatal neurodegeneration underlying motor dysfunction and cognitive deficits Huntington's disease (HD). Excitatory amino acid transporter 2 (EAAT2), the predominant glutamate accounting for >90% of transport, plays a key role preventing by clearing excess from intrasynaptic cleft. Accordingly, EAAT2 has emerged as promising therapeutic target prevention neuronal HD other neurodegenerative diseases.We have previously designed novel positive allosteric...
Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disorder. Although cases of ALS are sporadic, 5–10% familial, with mutations associated over 40 genes. There variation symptoms within families carrying same mutation; disease may develop in one sibling and not another despite presence mutation both. cause this phenotypic unknown, it likely related to genetic modifiers expression. The identification causing genes has led development transgenic mouse models...
Current evidence suggests a causal role of inflammation in the pathogenesis Parkinson’s Disease (PD). PD is progressive neurodegenerative disorder that associated with loss dopaminergic neurons and aberrant accumulation alpha‐synuclein fibrils Lewy bodies present surviving substantia nigra. Importantly, can interact toll‐like receptor 2 (TLR2) on both microglia to induce neuroinflammatory response. Previous work has investigated effects pre‐existing neurodegeneration. However, effect...
β-arrestins play key roles in both terminating G protein signaling and activating protein-independent across many coupled receptors (GPCRs); however, the of dopamine D3 receptor (D3R)-mediated ERK phosphorylation/signaling are poorly characterized. Our previous studies showed that novel compounds SK609 its analog SK608 selective D3R agonists display Gi/o biased without significant recruitment β-arrestin2 (βarr2) compared with which can potently activate proteins recruit β-arrestins. We...
Toll-like receptors (TLRs) are pattern recognition molecules that induce inflammatory signaling cascades upon of pathogen or damage associated molecules. In addition to peripheral immune cells including monocytes, TLRs broadly expressed on the central nervous system (CNS) microglia, astrocytes, and neurons their activation induces production pro-inflammatory mediators inducing neuroinflammation neurodegeneration in chronic state. Prolonged substantia nigra (SN) leading accumulation...