In 2023, the World Health Organization (WHO) estimated that there were 263 million malaria cases and 597,000 deaths globally. Parasites of the genus Plasmodium are the causative agent of malaria, deposited into the dermis of a human host through the bite of a female Anopheles mosquito carrying infected sporozoites (spz). From the dermis, spz migrate through the bloodstream and into the liver where they infect hepatocytes, producing potentially thousands of merozoites from a single hepatocyte which then enter the symptomatic erythrocytic stage of the disease. Higher numbers of CD8+ T cells per infected hepatocyte have been associated with Plasmodium clearance and because eliminating all infected hepatocytes during the pre-erythrocytic stage prevents malaria onset, identifying causes of CD8+ T cell recruitment provides critical insights for malaria prevention. The liver is one of the most sexually-dimorphic organs in both mice and humans, leading us to utilize immunohistochemical light microscopy to observe CD8+ cells in inflammatory foci, defined as abnormal concentrations of hepatic nuclei including at least one CD8+ cell. Using digital pathology software, we quantified these in female, male, and orchiectomized male (ORX) BALB/cJ mice that were either unvaccinated or repeatedly vaccinated with radiation-attenuated spz allowing us to assess the role of androgens in this recruitment. We found that following challenge with the rodent malaria wild-type parasite Plasmodium yoelii spz, vaccinated mice had more inflammatory foci and CD8+ cells than unvaccinated mice while intact male mice had fewer CD8+ cell and inflammatory foci than ORX or females of similar vaccination status. These findings suggest that androgens reduce recruitment of CD8+ T cells to inflammatory foci, providing a potential explanation for the reduced parasite clearance in male mice compared to their female counterparts. Further studies should explore the mechanism behind this reduced recruitment to inform important decisions in malaria vaccinology and translational medicine.

The ecosystem of microbes found in the gut, or the gut microbiota, plays a vital role in host health, influencing the immune, digestive, and central nervous systems. Research suggests that the microbiome may be linked with the development of neuropsychiatric disorders, presenting the possibility that altering the microbiome could influence the risk of these conditions. Recent research has explored this link within the context of Parkinson’s Disease (PD), a neurodegenerative disorder primarily known for its effects on motor control. PD patients often suffer from chronic constipation for years prior to diagnosis. Although the mechanisms of this gut-brain relationship are still unknown, many studies have highlighted the potential involvement of the gut microbiome in the development of PD. I explored the specifics of this relationship by developing a metabolic model trained on metagenomic data from PD case-control studies, using a microbial community-scale metabolic modeling (MCMM) approach. MCMMs may provide detailed mechanistic insights into the gut-associated etiology of PD, potentially allowing for the development of preventative therapies that prevent the onset of PD, which could revolutionize our current system of retroactive treatment of the established disease.

Malaria, caused by the Plasmodium parasite, remains a relentless and destructive infectious disease, disproportionately affecting children in Sub-Saharan Africa, due in part to the absence of a highly effective, widely deployable malaria vaccine. Lipid nanoparticle (LNP) vaccines are a promising approach for vaccine development, especially against pathogens such as Plasmodium, which have proven historically difficult to vaccinate against. When coupled with the glycolipid adjuvant 7DW8-5 at a 5ug LNP to 0.5ug adjuvant ratio, malaria-targeting LNP formulations confer protection in mouse models. However, the optimal vaccine-to-adjuvant ratio and the mechanisms underlying 7DW8-5-mediated protection remain unclear. Here, we present a study that aims to refine dosing strategies and elucidate the role of CD8+ T and NKT cells in adjuvant-induced protection in a human-translatable mouse model. Different groups of mice will be vaccinated with varying LNP-to-adjuvant ratios, and immune response will be assessed via ELISPOT 28 and 56 days post-vaccination. Furthermore, we will use ELISA to reveal variations in innate immune response between groups 3 hours after vaccine administration. In parallel, we will investigate the necessity of CD8+ T cells and/or NKT cells in protecting from malaria challenge. Mice will be vaccinated using the standardized LNP-to-adjuvant ratio and treated with depletion antibodies targeting CD8+T or NKT cells 24 hours before challenge with Plasmodium sporozoites. Protection will be assessed via blood smear analysis. Our findings will reveal optimal dosing strategies for malaria-specific LNP vaccines and provide insight into the immunological mechanisms behind 7DW8-5-driven protection. This research will contribute to the development of effective nanoparticle-based malaria vaccines — a necessary innovation to help relieve the global malaria burden.

Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites and in 2023 caused an estimated 597,000 deaths. Although two currently approved malaria vaccines are available, they offer insufficient protection in endemic populations, which prompts the need for new vaccines. Here we tested several lipid nanoparticle (LNP) vaccines and quantified the number of surviving parasites in vaccinated mice challenged with Plasmodium yoelii sporozoites. To quantify surviving parasites, we utilized the Plasmodium 18S rRNA reverse transcription PCR assay, which is a highly sensitive assay that can quantify the amount of Plasmodium parasites in liver or blood samples. The assay works by amplifying and detecting parasite 18S rRNA in a sample through specific primers, probes and quenchers for mouse GAPDH mRNA and pan-Plasmodium 18S rRNA and can be used to quantify the burden of Plasmodium in a sample. Through the 18S assay, we identified LNP formulations that most effectively protected against rodent malaria. Notably, these LNPs required the adjuvant 7DW85 to be protective.  In the absence of the adjuvant, fewer mice vaccinated with LNPs were protected against rodent malaria. Together, we identified our leading LNP vaccines, which we continue to optimize with the goal of attaining sterile protection against rodent malaria. 

Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling. One key feature of airway remodeling is the thickening of the subepithelial basement membrane zone (BMZ) beneath the airway epithelium, which has been identified in severe asthma relative to milder severity asthma and other airway diseases. We aim to characterize the relationship between BMZ thickness, airway physiology, and airway immune cell populations. I am utilizing design-based stereology to precisely measure BMZ thickness in endobronchial biopsies obtained from 30 individuals with asthma and 10 healthy individuals. These individuals underwent extensive characterization for asthma airway physiology, profiling of airway immune cell populations, and airway inflammatory gene expression. Stereology provides unbiased thickness estimates that have greater reproducibility and overcome the limitations of two-dimensional measurements. I am measuring BMZ thickness using the orthogonal intercept method, which involves averaging the lengths of lines extended perpendicularly from the epithelial surface across the thickness of the BMZ at systematically sampled points. I am correlating BMZ thickness with clinical characteristics (allergic sensitization), airway physiology (baseline lung function, measurements of airway hyperresponsiveness), densities of both mast cells and eosinophils in the airway wall, and gene expression profiles obtained from airway epithelial brushings. I hypothesize that individuals with asthma patients will have more BMZ thickening in comparison to healthy controls. I also anticipate that there will be a positive correlation between the thickness of the BMZ and the expression of type-2 (T2) inflammatory genes (IL4, IL5, IL13). Finally, I hypothesize that there will be a positive correlation between BMZ thickness and the density of mast cells in the airway epithelial compartment. This research study provides new insights into the potential mechanisms responsible for airway remodeling in individuals with asthma and how they connect with airway inflammatory endotypes, which may guide further development of targeted therapeutics. 

Rapid-growth wildfires disproportionately contribute to loss of life and destruction of property. Further improving our understanding of longer-term signals of impending fire-associated weather is crucial if we are to mitigate future destruction. Recent work compared local conditions, including surface wind and 100-hour dead fuel moisture (FM100) to fire growth (Murphy and Mass 2025). We investigate the evolution of larger scale weather patterns prior to rapid wildfire growth. Using two individual-fire-growth datasets, Fire Events Data Suite (FEDS) and Fire Events Delineation (FIRED), we separate fires by season, growth rate, and region. We conduct analyses of several meteorological variables for periods preceding maximum growth in rapid-growth wildfires. Using the European Centre for Medium-Range Weather Forecasts Reanalysis v5 (ERA5) dataset, we compare weather patterns at different heights in the atmosphere prior to maximum growth for fires of different growth rates and in different seasons, to identify any signals comporting to eventual fire extremity. We also consider how the patterns affect FM100 and near fire winds and the impacts of region of wildfire within California.