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.

Partner and Localizer of BRCA2 (PALB2) is a necessary linker protein between BRCA1 and BRCA2. In order to create this connection it interacts directly with BRCA1 via a coiled-coil domain in both proteins. Facilitating this linkage directs cells to fix double stranded DNA breaks (DSBs) through homologous recombination. The mutation L35P has been shown to disrupt this linkage forcing the cell to complete repair through alternate pathways that are not as accurate. This inaccuracy can lead to the accumulation of mutations and increase the risk of breast and ovarian cancers. The L35P variant within the coiled-coil domain of PALB2 has been linked with hereditary breast and ovarian cancer. However, it is unknown if loss of leucine in the interface is causing the decrease in binding or if it is the introduction of a proline into the coiled-coil region that is destroying the secondary structure thereby inhibiting binding. We are studying five variants of unknown significance (VUS) from PALB2 that are within the coiled-coil and are also proline substitutions. One of these mutations is within the binding interface and the other four are on the backside of the coil. We are investigating the structure and BRCA1-interaction of these VUS to directly connect structural changes in the coil to functional deficiencies. Currently we have found that these proline variants are inhibiting binding with BRCA1 through measuring heat exchange with isothermal titration calorimetry. We also plan on evaluating these variants through circular dichroism as well to assess if the secondary structure of PALB2 is affected as well.

Malesia is a vast phytogeographic region in Southeast Asia, spanning roughly one-fifth of the world’s circumference and considered one of the most biodiverse regions of the world. It is divided into three subregions: Sahul, Sunda, and Wallacea, primarily distinguished by their geological history and differences in floristic composition. Research based on fossil-calibrated phylogenetic trees has begun to provide insights into the historical phytogeography of Malesia, specifically regarding the reciprocal migration of plant lineages across the Sunda and Sahul regions known as the “Sunda-Sahul floristic exchange (SSFE).” This study aims to test the SSFE hypothesis with the use of the Asian tropical blueberry clade of tribe Vaccinieae (Ericaceae). Silica-dried specimens from previous fieldwork, garden-grown plants of wild origin, and herbarium specimens were used to extract genomic DNA. The samples were sequenced with the Angiosperms353 bait set, and a dated phylogenomic tree was constructed, incorporating all available genomic data from online repositories. Divergence time analysis and ancestral area reconstruction was performed to test the hypotheses of the SSFE. This research will serve as a steppingstone towards resolving the phylogeny and evolutionary history of tribe Vaccinieae. It will also form a foundation for assessing the conservation status of micro-endemic and threatened Asian tropical blueberry species, especially in Malesia. Lastly, this study will highlight the crucial role of botanical gardens and herbaria as vital repositories of natural history collections.

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.