Iron Regulatory Proteins 1 and 2 (IRP1 and IRP2) are key regulators of cellular iron levels. Iron is essential for proper brain development and function, but can lead to cellular damage if not properly regulated. To investigate the effects of reduced expression of IRP1 and IRP2 on neuronal health and neurodegeneration, we are using mouse neurons that have been transfected with shRNA to specifically knock down IRP1 or IRP2. Mouse neurons are well-studied and share many key cellular pathways with human neurons, making them an appropriate model to study the effects of IRP1 and IRP2 knockdown. We will investigate the effect of the knockdowns on the mouse neurons through proliferation assays and differentiation assays. These experiments will reveal how the knockdown of IRP1 and IRP2 affects neuronal growth, maturation, and development compared to healthy control cells. Understanding these processes is incredibly important for humans, as iron dysregulation can lead to neurodegenerative diseases such as Alzheimer's.

The Arctic is contaminated with mercury (Hg) higher than historic baselines because of emissions from temperate and subtropical areas. The nonbioavailable form, inorganic Hg, is deposited on the landscape and is thought to have limited impacts on terrestrial organisms. In aquatic systems, inorganic Hg is converted to methylmercury (MeHg), a contaminant that biomagnifies through food webs and poses reproductive and neurological risks to wildlife and humans. The Arctic wolf spider (Pardosa glacialis), is one of the most abundant terrestrial predators in western Greenland, and prior research has linked MeHg concentrations in wolf spiders to emergent aquatic insects, indicating cross-ecosystem contaminant transfer. While freshwater ecosystems are recognized as important sources of MeHg to terrestrial consumers, recent observations suggest that Arctic terrestrial insects may also exhibit elevated Hg concentrations comparable to aquatic insects, potentially providing an additional pathway of contamination for terrestrial predators. However, the relative contribution of aquatic versus terrestrial prey to P. glacialis diets across Arctic ponds remains unclear. We investigated how aquatic and terrestrial prey contribute to the diet of P. glacialis and how this dietary composition may influence contaminant exposure in Arctic terrestrial food webs. We hypothesize that wolf spiders consume a mixture of both aquatic and terrestrial insects, broadening the source of P. glacialis’s contamination. To test this, we captured and analyzed wolf spiders, terrestrial insects, and emergent aquatic insects at six Arctic pond sites. Across all ponds, spider populations exhibited a dietary mixture of aquatic and terrestrial insects. These results indicate that both aquatic and terrestrial insects influence P. glacialis MeHg contamination. This suggests that all artic food webs, not just those connected to aquatic systems, may be contaminated with MeHg, suggesting that the Arctic is more contaminated than previously thought.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and neuronal loss. Although amyloid-ß plaques and tau neurofibrillary tangles are well-established pathological hallmarks of AD, growing evidence suggests that additional mechanisms, including oxidative stress, iron dysregulation, and ferroptosis contribute significantly to the progression of the disease. Ferroptosis is an iron-mediated form of regulated cell death driven by lipid peroxidation and impaired antioxidant defenses. Neurons are particularly susceptible to ferroptotic damage due to their high metabolic demand, lipid-rich membranes, and reliance on highly regulated redox homeostasis. Disruption of the cystine/glutamate antiporter (system xc-) can deplete intracellular glutathione (GSH), impair glutathione peroxidase 4 (GPX4) activity, and promote the accumulation of toxic lipid peroxides, ultimately triggering ferroptotic cell death.

This study investigates the role of ferroptosis in oxidative neuronal injury using the immortalized HT-22 mouse hippocampal neuronal cell line, a well-established model of glutamate-induced oxytosis. Oxidative stress is induced through glutamate exposure, which inhibits cystine uptake via system xc- and depletes intracellular glutathione levels. Cell viability is assessed using MTT assays, and quantitative PCR is used to evaluate transcriptional changes in key genes involved in ferroptosis and antioxidant defense, including Nrf2, Slc7a11, Acsl4, Ptgs2, Sod2, and Catalase. To confirm the involvement of the ferroptotic pathway, the potent ferroptosis inhibitor Ferrostatin-1 (Fer-1) is employed to evaluate its ability to rescue neurons from glutamate-induced toxicity.

By characterizing both functional and transcriptional responses to oxidative stress, this research aims to better define the underlying molecular mechanisms by which glutamate toxicity leads to ferroptotic neuronal death. Understanding how ferroptosis contributes to neuronal vulnerability may reveal novel therapeutic targets aimed at strengthening antioxidant defenses and mitigating neurodegeneration in Alzheimer’s disease.

Alzheimer’s Disease (AD) is a neurodegenerative disease that is characterized by progressive neuronal death. AD can be identified by the presence of cytotoxic amyloid-ß plaque on neuronal synapses and misfolded tau tangles in the body of neurons. As the most common form of dementia, AD has become a hot topic for healthcare professionals, and researchers have looked for a better understanding of how to stop the progression of the disease. Recently, studies have looked into the antioxidant pathway as a target for controlling AD. Evidence shows that the presence of Aß-plaques and tau tangles generates oxidative stress in the form of reactive oxygen species (ROS). The persistence of ROS may lead to chronic inflammation and neuronal cell death. Our study looks at the effect of a novel drug, L2, on its ability to activate the antioxidant pathway in mouse cell models. The novel drug is designed to locate ROS and has antioxidant properties, and has been proven to reduce ROS in in vitro studies. If L2 is added into ROS-rich cell culture, then the antioxidant pathway will be activated and express the genes for antioxidant proteins. To test for activation of the antioxidant pathway, mouse microglial cells were treated with L2 and were lysed for messenger RNA (mRNA) extraction. Differentially expressed genes were quantified and analyzed using the RT-qPCR technique and RNA sequencing. Results of the data are still being analyzed.

Invasive species harm local ecosystems, economies, and cultures. There has been a substantial effort to research the recent increase in the number and frequency of successful invaders; however, relatively little information regarding if and to what extent genetics influences a species ability to become a successful invader exists. Whole genome sequencing provides a mechanism that could illuminate the importance of genetics for successful invasion and uncover the roles selection plays in predisposing populations to be successful invaders. Northern pike (Esox lucius) are native to the Holarctic region but have been widely introduced across Europe and North America. For example, pike were introduced to the area around Anchorage, Alaska in the 1970s and have since spread throughout southcentral Alaska. This species represents a major threat to populations of native fish species, especially multiple species of salmonid. Current management efforts appear to fall short as many pike populations have increased following removal. Part of this growth is likely from the ability of pike to disperse into marine environments, allowing them to colonize new bodies of freshwater. However, whether this ability to disperse is genetic – and therefore heritable - remains unknown. If there are alleles that predispose some populations of pike to be successful invaders, then such populations should be the target of multifaceted eradication efforts. To that end, several populations of pike – consisting of known residents and dispersers - from south-central Alaska were analyzed using whole genome sequencing to a) determine if there are alleles associated with dispersal ability and b) to determine if and to what extent populations are predisposed to dispersal behaviors. Overall, this research will improve our understanding of the genetic basis of invasive biology, identify populations of pike that should become a priority for eradication, and help protect native fish species.