Manganese (Mn) is a common metal and an important trace element in biological systems. In humans, Mn plays an important role in many organs, including the brain. Mn is a constituent of superoxide dismutase (SOD), an antioxidant enzyme in the mitochondria. In humans, excess exposure to manganese damages neuronal mitochondria and results in a movement disorder known as Manganism, which shares some features with Parkinson’s Disease. We have developed a model to study Mn toxicity using Daphnia magna (D. magna), freshwater zooplankton often referred to as “water fleas.” Daphnia are found in lakes and ponds worldwide and have been used for decades as indicator species to detect contaminants in freshwater environments. Under normal conditions, Daphnia exist predominantly as clonal females reproducing by cyclic parthenogenesis. Our lab has previously shown chronic exposure to Mn concentrations ranging from 0.2 mg/L to 100 mg/L causes negative effects on reproduction, lifespan and locomotion of D.magna. We hypothesize that acute Mn exposure of 30 mg/L Mn induces a change in the expression of genes related to metal absorption and reproductive capabilities. To test this hypothesis, we have identified genes that are important for manganese utilization and reproduction: metallothionein and natalisin, genes that are present in the Daphnia magna genome and expressed in adults. We have developed and begun validation of qPCR assays to measure expression of metallothionein and natalisin. Future experiments will focus on quantitatively measuring gene expression in control and Mn treated D. magna.

Substance use disorder (SUD) is a chronic, relapsing condition that disrupts not only behavior but also key neurological and cognitive functions. While conventional treatments like Methadone Maintenance Therapy (MMT) and behavioral counseling have been effective in managing withdrawal symptoms and reducing substance use, high relapse rates and limited support for neural recovery remain significant concerns. Recent clinical studies have highlighted the potential of nutritional supplementation in improving mental health and cognitive performance in patients undergoing addiction treatment. These findings suggest that nutrient-based interventions may serve as valuable complementary therapies in the recovery process. This project aims to evaluate the therapeutic potential of Epigallocatechin gallate (EGCG), a natural antioxidant found in green tea, on dopaminergic neurons with downregulated dopamine D2 receptors (DRD2)—a molecular change commonly observed in individuals with SUD. Using CRISPR-Cas9 technology, DRD2 expression will be selectively depleted in cultured human dopaminergic cell lines, SH-SY5Y, to create a biologically relevant in-vitro model of addiction-related neuroadaptation. These modified cells will then be treated with EGCG, and their responses will be assessed using cell viability and apoptosis detection assays. The importance of this project lies in its contribution to the emerging field of nutritional neuroscience and its potential to identify novel, low-risk strategies for supporting brain health in individuals recovering from SUD.

Substance use disorder (SUD) is a chronic, relapsing condition with strong neurobiological underpinnings, including dysregulation of the dopaminergic system. The dopamine D2 receptor (DRD2) plays a critical role in reward signaling and is frequently altered in individuals with SUD. Gallic acid, a naturally occurring polyphenol with neuroprotective properties, has shown potential in modulating oxidative stress and inflammation—key factors in neurodegeneration and addiction pathology. This proof-of-concept study investigates the impact of gallic acid on dopaminergic signaling in SH-SY5Y cells with reduced DRD2 expression. CRISPR-Cas9 gene editing was employed to knock down DRD2 in SH-SY5Y cells, creating a simplified in vitro model to explore the compound's therapeutic potential. Cell viability and expression of downstream dopaminergic markers were assessed following gallic acid treatment. Findings from this study will provide preliminary insights into the feasibility of targeting dopaminergic pathways with plant-derived compounds and inform future research using more physiologically relevant neural models.

Emery-Dreifuss muscular dystrophy (EDMD) causes progressive skeletal muscle weakness and cardiomyopathy. EDMD belongs to a diverse group of diseases called laminopathies caused by mutations in LMNA and other lamin genes. LMNA encodes lamin A/C, intermediate filament proteins that form the nuclear lamina along the inner nuclear membrane, providing critical mechanical stability to the nucleus. Previous work established Caenorhabditis elegans models of striated muscle laminopathies by introducing pathogenic human LMNA variants at conserved residues within the C. elegans lmn-1 gene. These variants, associated with both skeletal and cardiac defects in humans, produced severe phenotypes including decreased brood size, increased embryonic lethality, reduced motility, and nuclear morphology defects. However, cardiac muscle dysfunction – a major cause of morbidity and mortality in EDMD patients – remains uncharacterized in these models. Here, we address this critical gap by quantifying pharyngeal pumping function, leveraging the pharynx as a cardiac muscle surrogate due to its intrinsic myogenic activity and nervous system regulation. We measured pharyngeal pumping rates across C. elegans developmental stages in animals carrying pathogenic LMNA variants. Our findings reveal how nuclear lamina disruption specifically affects cardiac muscle function, providing mechanistic insights into poorly understood cardiomyopathy phenotypes that could inform therapeutic strategies for laminopathy patients. This work establishes a quantitative framework for assessing cardiac dysfunction in C. elegans laminopathy models, enabling future drug screens and mechanistic studies of this devastating disease family.