Cryptococcus neoformans is a pathogenic fungus that can cause cryptococcosis, affecting the lungs and central nervous system with potentially morbid consequences. This pathogen is particularly aggressive in individuals with impaired T-cell function, such as those with AIDS or on immunosuppressive medications. There are currently no vaccines available for this pathogen and a limited arsenal of antifungals is available. Our lab has developed a C. neoformans strain that produces mouse IFN-ɣ, called H99ɣ, that induces protective immunity against subsequent infection with wild-type C. neoformans in mouse models of cryptococcosis. We aim to use variants of this strain to better understand the immune response against Cryptococcus and develop new therapies. In this study, our goal is to evaluate the efficacy of various newly developed C. neoformans vaccine mutants to induce protective immune responses against C. neoformans. RNA will be isolated from tissues extracted from mice immunized with the different C. neoformans strains: H99ɣ, LW10, LW10ɣ, sre1ΔLW10ɣ, and sgl1ΔLW10ɣ and the mRNA transcripts of immune cells responding to subsequent infection with C. neoformans evaluated. By using the information derived from these transcripts, we aim to identify key determinants of protection against cryptococcosis. Using the transcriptomic data, we can determine the best candidate to further evaluate for its capacity to elicit protective immune responses in immune-compromised hosts.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a growing health concern, affecting nearly 24% of U.S. adults. It is characterized by excessive fat accumulation in the liver, often linked to obesity, insulin resistance, and poor dietary habits. Chronic inflammation and oxidative stress play key roles in disease progression, with excessive saturated fat intake exacerbating liver damage. Genes involved in lipid metabolism, such as sterol regulatory element-binding protein 1 (Srebp1c) and peroxisome proliferator-activated receptor γ (Pparγ), regulate fat storage in the liver and contribute to MAFLD development. Additionally, oxidative stress-related genes like nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 1 (GPX1) influence antioxidant defenses, impacting liver health. Our study investigates the effects of two dietary models—the Typical American Diet (TAD) and the Mediterranean Diet (MED)—on liver health. The TAD, high in saturated fats, promotes lipid accumulation and oxidative stress, while the MED, rich in unsaturated fats, may improve liver function by reducing inflammation and oxidative damage. Findings suggest that diet influences gene expression, affecting lipid metabolism and oxidative stress pathways. Understanding these mechanisms may help develop dietary strategies for MAFLD prevention, emphasizing the role of nutrition in liver health.

Zebra mussels (Dreissena polymorpha) are an invasive bivalve of significant ecological and economic importance due to their widespread invasion and disruption of aquatic ecosystems and commercial infrastructure. Their ability to spread from the northern Great Lakes to the southern areas of the United States is due in large by their reproductive strategy. Zebra mussels release eggs and sperm into the water column where fertilization and subsequent larval development occurs. Two key steps in the fertilization process are the ability of sperm to bind and penetrate the egg surface and the ability of the egg to prevent more than one sperm from entering the egg (polyspermy). In many other species, proteases play a key role in these processes; however, there is there is variability between aquatic species, such that elucidating specific mechanisms is unique to individual organisms. Here, I investigate the potential role of proteases in sperm binding and entry. To discern these mechanisms in zebra mussels, I exposed fertilization processes to small-molecule inhibitors. Based on the observations of the phenotypic changes upon exposure, implications can be made to specific molecules or groups of molecules involved in Dreissena polymorpha sperm-egg interactions. These implications point to the further investigation and development of small-molecule inhibitors of Dreissena polymorpha fertilization.

Arctic wolf spiders (Pardosa glacialis) are dominant terrestrial predators in the High Arctic, yet the extent to which their diets are influenced by aquatic subsidies remains uncertain. Previous research suggests that aquatic insects do serve as a key food source for shoreline predators, transferring both nutrients and contaminants such at mercury (THg) from aquatic to terrestrial ecosystems. Aquatic insects have unique carbon (δ¹³C) and nitrogen (δ¹⁵N) isotopic signatures that differentiate them from terrestrial insects that allow for identification of aquatic-derived energy in terrestrial food webs. The purpose of this case study is to examine the stable isotope composition of P. glacialis collected at varying distances (0, 10m, and 35m) near a pond located in northwest Greenland to establish local food web dynamics and assess potential pathways of contaminant transfer. Understanding these dynamics will provide insight into how THg is distributed among trophic levels and across distances in riparian environments. P. glacialis were collected in traps placed at three distances from pond shoreline (0, 10m, and 35m). The specimens were then analyzed for THg and stable isotope ratios. We hypothesized that spiders collected closer to the shoreline will display isotopic values indicative of a more aquatic-based diet as well as higher THg concentrations. Conversely, with increasing distances from pond shoreline, we expect to see isotopic signatures suggestive of a more terrestrial diet and lower THg. Given mercury’s neurotoxic and bio accumulative properties, results of this study will provide insight not only into aquatic-terrestrial linkages in Arctic ecosystems but also the potential threats that the trophic movement of contaminants may pose to wildlife.

Metabolic reprogramming is a hallmark of cancer, allowing tumor cells to sustain proliferation under varying nutrient and oxygen conditions. One of the most well-known adaptations is the Warburg effect, wherein cancer cells preferentially utilize glycolysis to generate ATP and produce lactate, even in the presence of oxygen. While lactate has long been considered a metabolic waste product, emerging studies suggest that it may have regulatory functions beyond energy production. In this study, we investigate how lactate influences the metabolic enzyme malate dehydrogenase 1 (MDH1), a key component of the malate-aspartate shuttle and a contributor to cytosolic NAD⁺ regeneration. Using CRISPR-mediated MDH1 knockout models, cell proliferation assays, a cell-free mitochondrial system, and direct enzymatic activity measurements, we demonstrate that lactate—both L- and D-enantiomers—activates MDH1. This activation is independent of lactate’s conventional metabolic conversion via lactate dehydrogenase. Notably, D-lactate, which mammalian cells cannot metabolize, produced similar effects to L-lactate, indicating a non-metabolic, potentially signaling-based mechanism. Structural modeling using AlphaFold2 further supports the presence of a putative lactate-binding site on MDH1. These findings suggest a novel paradigm in which lactate directly regulates mitochondrial metabolism, redefining its role in the Warburg effect and its contribution to cancer cell proliferation.

Alzheimer’s disease is characterized by dysregulated production of reactive oxygen species (ROS), driving oxidative stress and subsequent neuronal degeneration. Antioxidant enzymes such as superoxide dismutase (SOD) play a central role in maintaining redox homeostasis; however, their activity is compromised in individuals with Alzheimer’s disease. Although small molecules have been developed in the past to mitigate oxidative stress, their clinical translation has been limited by poor blood-brain barrier permeability and suboptimal drug-like properties. In this work, we present a multi-step synthetic strategy for a pyridine-based tetra-aza macrocycle designed to improve blood–brain barrier permeability while retaining multi-target antioxidant activity.

The shape of a drug will determine how it interacts in the body. For it to work, it must dissolve, be absorbed into the bloodstream, avoid breakdown, enter the cell and bind to its target. Each of these steps likely requires a different shape. The pharmaceutical industry has historically only focused on the shape required to bind the target. This research has identified molecules that can readily adopt multiple shapes. These ring-shaped molecules (called macrocycles) represent a new model for drug design. Usual drugs (ie ibuprofen) are small and interact with a specific target to stop a chemical reaction. Macrocycles can work by an additional mechanism. They are larger and can interfere with interactions between proteins but are still small enough to travel the body. The preparation of these macrocycles is inexpensive and quick, properties that are important for the pharmaceutical industry. This poster describes the design and synthesis of a macrocycle and an analysis of the shapes that it adopts.

Every 65 seconds, someone develops Alzheimer's disease, which is the seventh leading cause of death in the United States. A major barrier to potential therapeutics is the permeability of these molecules across the blood-brain barrier. We have developed small molecules with strong reactivity to combat the oxidative stress known to cause Alzheimer’s disease. However, the permeability is less than ideal. As a result, my goal is to produce a molecule that has enhanced permeability but retains the reactivity of the parent molecules. To achieve this, the BOILED-Egg model assessed different derivatives of our parent molecule, Py2N2. This model showed the differences in lipophilicity among different Py2N2 compounds and how they impact permeability into the blood-brain barrier and gastrointestinal tract. Background information on our parent molecule and its function regarding Alzheimer's development will be outlined to give a scope of what these compounds can target and how they function. Compounds with high lipophilicity reflected in the model will have schemes of synthetic synthesis for future directions.

Perfluoroalkyl substances (PFAS), known as "forever chemicals", are ubiquitous environmental contaminants whose remarkable persistence poses significant risks to human health and ecosystems. Thus, it is important to develop analytical assays to determine PFAS concentrations based on widely accessible, readily available instrumentation, such as UV-VIS spectrophotometry. Tetrasodium tetraphenylporphyrintetrasulfonate (TPPS) is a water-soluble porphyrin known for its spectrophotometric property in water. It is also known that TPPS binds to the protein bovine serum albumin (BSA). We investigated the effect of BSA on the absorption spectrum of TPPS and how PFAS presence impacts BSA-TPPS interaction in water. Interestingly, we found that BSA induces TPPS precipitation. As BSA concentration increases, TPPS solubility first dramatically decreases, then increases, ultimately leading to the formation of homogeneous solutions at relatively high BSA concentration. Furthermore, addition of two different PFAS, sodium perfluorohexanoate and potassium perfluorobutanesulfonate salts, to homogeneous BSA-TPPS mixtures appreciably alter TPPS spectra. Our results show that these mixtures can be used to produce calibration curves relevant to the determination of PFAS concentrations in water.

Some of the most effective drugs from Nature are large and ring-shaped, so-called macrocycles. Macrocycles are interesting because they can interfere with protein-protein interactions, a different strategy for therapy than that used by small molecules (like aspirin). The challenge with the design of macrocycle drugs is that they are difficult to make and behave unpredictably. Here, an efficient strategy to make macrocycles is described. These molecules behave consistently (with preserved shapes) and can be tailored to optimize binding (a hallmark of drug design). The two macrocycles described differ in the choice of one group with significant (and predictable) consequences. Both groups mimic amino acid sidechains that are implicated in protein-protein interactions. One amine, N-methylbenzylamine, yields a macrocycle that will adopt six conformations in solution (an advantage when looking for drugs). The second amine, isobutylamine, gives more than eight conformations. Structural analysis was accomplished by NMR spectroscopy.