Zebra and quagga mussels originated in Eastern Europe and were introduced to the United States in the mid-1980s. After spreading from the Great Lakes throughout much of the eastern United States, including Texas, both species have become major ecological and economic pests. The objective of my project is to investigate the hybridization potential between two invasive dreissenid species, Dreissena polymorpha (sebra mussel) and Dreissena rostriformis begensis (quagga mussel). I will analyze fertilization, success, gamete compatibility, larval development, and competitive sperm binding to determine the success and viability of hybridization. Understanding this is important, as hybridization could increase genetic diversity, novel advantageous traits, and the potential for range expansion.

Bumblebees play a central role in pollinating both crops and natural plant populations. Yet, many bumblebee species are declining due to numerous anthropogenic effects, including exposure to pathogens. Bumble bees rely on a specialized community of gut bacteria, termed the “core” gut microbiome, to provide resistance against pathogens. However, the roles of particular bacterial species and strains within the core gut microbiome for defending against opportunistic pathogens remain unclear. This study investigated whether two abundant core gut bacteria – Gilliamella bombi and an unidentified bacterial strain isolated from bumble bee workers (Bombus impatiens) – reduce colonization by the opportunistic bacterial pathogen Serratia marcescens. After experimentally inoculating bumblebees with these two bacterial symbionts across a range of doses, we quantified bee resistance to pathogen infection by counting the number of colony-forming units (CFUs) of S. marcescens that colonized the gut. Contrary to expectations, the symbionts examined did not reduce pathogen colonization rate. These findings suggest that protection may require the full microbial community, specific combinations of taxa, or context-dependent interactions. Understanding when and how microbiomes confer defense is critical for predicting pollinator health under environmental change, and our research suggests that additional work is needed to identify probiotic bacteria that could be deployed to promote pollinator health.

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.

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.

“EVALUATING THE EFFECT OF NOVEL DRUGS ON LPS-INDUCED INFLAMMATION USING ENZYME-LINKED IMMUNOSORBENT ASSAY”

Neuroinflammation plays a key role in many neurodegenerative diseases and is characterized by the over-activation of immune cells within the central nervous system. Activated microglia and astrocytes release pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF- α), as well as reactive oxygen species that contribute to neuronal damage. These inflammatory responses are mediated through signaling pathways including the NF-κB pathway and the NLRP3 inflammasome.
Alzheimer’s disease (AD) is the most common neurodegenerative disease and the leading cause of dementia worldwide. In AD, accumulation of β-amyloid plaques (Aβ) stimulates chronic neuroinflammatory responses and contributes to neuronal dysfunction and disease progression. Elevated levels of inflammatory cytokines, particularly IL-1β, have been strongly associated with Aβ plaque deposition and the onset of AD.
Based on this relationship, targeting neuroinflammatory signaling pathways might be a promising therapeutic strategy for AD. PD2244, a novel compound synthesized by P2D Biosciences, is hypothesized to reduce neuroinflammation by suppressing the production of pro-inflammatory cytokines involved in AD pathology. Specifically, PD2244 is expected to decrease IL-1β production by inhibiting either the NF-κB pathway or the NLRP3 inflammasome.
To test this hypothesis, PD2244 was tested on several cells related to AD pathology, including microglial, neuronal, and monocytic. These cells were pretreated with increasing concentrations of PD2244 prior to inflammatory stimulation. IL-1β production was quantified using Enzyme Linked Immunosorbent Assay (ELISA), a highly sensitive technique commonly used to detect pro-inflammatory cytokine production.

As antibiotic resistance continues to rise, the development of new antibiotics is more important than ever. However, converting an active antibiotic compound into a clinically viable pharmaceutical requires optimization of the drug’s pharmacokinetic profile, including improving its stability, permeability, and targeted delivery to pathogens. One strategy to overcome these delivery challenges is the use of prodrugs—inactive or chemically modified derivatives of a parent compound that are converted to their active form in vivo, most often through enzymatic cleavage. Effective prodrug modifications can improve drug delivery to pathogens or enhance permeability through the hydrophobic bacterial cell membrane while maintaining or improving the activity of the parent compound. Our goal is to categorize novel prodrug structures by assessing efficacy of penicillin prodrug derivatives. This project analyzes the activity of penicillin prodrugs synthesized in the Montchamp Lab against the gram-positive bacterial species Bacillus anthracis and vancomycin-resistant Enterococcus faecalis using MIC (Minimum Inhibitory Concentration) assays. Penicillin G is a well-known antibiotic with a single acidic site, providing a convenient parent compound for synthesis and well-established MIC values. We determined that, consistent with hypothesis, prodrug structures with increasing numbers of enzymatic activation “triggers” exhibited increased antibiotic activity. For example, structures containing two benzene groups showed greater activity than those containing one, and both showed greater activity than nonderivatized Penicillin G. Knowledge of these promising prodrug structures will guide the future synthesis of antibiotics with more challenging pharmacokinetics to improve drug delivery and efficacy.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and chronic neuroinflammation. Inflammatory signaling pathways such as nuclear factor-κB (NF-κB) play a critical role in the progression of neurodegeneration by regulating the expression of pro-inflammatory cytokines such as TNF-α and IL-1β. Targeting NF-κB signaling therefore represents a promising therapeutic strategy for reducing inflammation associated with AD. This study evaluated the effects of several novel anti-inflammatory compounds provided by P2D Biosciences and Dr. Geen’s research lab on TNF-α–induced NF-κB activation. HEK293 cells were transfected with an NF-κB responsive PRDII luciferase reporter and a CMV luciferase control, followed by treatment with novel compounds and stimulation with TNF-α. Luciferase activity was measured to quantify the effect of our molecules on TNF-a-induced NF-κB transcriptional activation. Results demonstrated dose-dependent reductions in NF-κB activation for several compounds, suggesting potential anti-inflammatory activity. These findings contribute to ongoing efforts to identify novel small molecules capable of modulating NF-κB signaling and may support future therapeutic development targeting neuroinflammation in Alzheimer’s disease.

BRCA1 is widely recognized for its role in maintaining genomic stability, particularly through its involvement in several DNA repair pathways and chromatin regulation. While mutations in BRCA1 are strongly associated with increased cancer risk in humans, the broader cellular consequences of BRCA1 mutations under environmental stress remain unclear. The goal of the project was to investigate how loss or alteration of BRC-1, the Caenorhabditis elegans (C. elegans) homolog of BRCA1, affects stress responses at the organismal level, with focus on oxidative stress and reactive oxygen species (ROS) accumulation.

Using C. elegans as a model organism allowed me to study the stress responses within a system where development, reproduction, and genome stability are tightly connected. A key advantage of using C. elegans is that the organism is transparent. This allows for visualization and quantification of fluorescence to measure ROS within the worms, and to see how these values vary depending on BRC-1 status. Three strains were compared: 1) wild-type (N2), 2) a BRC-1 mutant (syb5376) predicted to disrupt nucleosome interaction and H2A monoubiquitylation while retaining other enzymatic functions, and 3) double knockout strain (xoe4) lacking functional BRC-1 entirely. The comparison of these worms with various levels of BRC-1 activity allowed for the investigation of how each of these different strains responded to various oxidative stressors. The broader aim of the project was specifically to look at how altered BRC-1 nucleosome ubiquitylation affects the cell's ability to deal with ROS, and compare this with the wild-type and complete knockout.

Several key questions were used to guide the research: 1) Whether stress responses differed between wild-type, mutant, and knockout strains, 2) How oxidative stressors altered ROS levels in each of the strains, and 3) Whether the syb5376 and xoe4 strains behaved similarly or exhibited distinct patterns compared to wild-type worms. Across multiple experimental conditions, the double knockout strain consistently showed the most elevated fluorescence, indicating increased ROS accumulation and reduced ability to manage oxidative stress due to the lack of BRC-1. The syb5376 mutant displayed an intermediate effect, suggesting partial impairment of regulation when lacking nucleosome interaction. These findings support the idea that BRC-1 plays a protective role under stress conditions and that disruption of nucleosome ubiquitylation may compromise the cellular response to oxidative damage and lead to a higher accumulation of ROS within cells.

Looking at the bigger picture, these results align with the broader understanding that BRCA1 loss does not immediately lead to cancer, but rather increases vulnerability when cells are challenged by environmental or metabolic stressors. Increased ROS levels can lead to DNA damage, and without proper chromatin remodeling and repair coordination, cells may struggle to restore their genomic integrity. The differences observed between the mutant and knockout strains further suggest that mutation type matters in determining the severity of stress sensitivity and the overall impact that this will have on the cell and organism as a whole.

The Texas Horned Lizard (Phrynosoma cornutum) has experienced significant habitat loss and population declines across their historic range in the southwestern United States; as such, the species has been listed as threatened by the Texas Parks and Wildlife Department. To mitigate declines, captive breeding programs have reintroduced large numbers of hatchlings into suitable habitat at the Mason Mountain Wildlife Management Area (MMWMA), which lies within the northern genetic cluster of Texas Horned Lizards. Long-term reintroduction success relies on the management of demographic factors and genetic variance. While demographic viability inherently increases with supplementation from an introduced population, the maintenance of genetic diversity within a reintroduced population must also be accounted for. If genetic management within captive breeding programs is not considered, the reintroduced population risks reduced allelic diversity and lower evolutionary potential, inbreeding depression, adaptation to captivity, or outbreeding depression if management units are mixed. We genotyped all captive-bred Texas Horned Lizards reintroduced in 2023 (N = 456 hatchlings) using 10 microsatellite loci to assess how genetically representative the introduced group is relative to natural populations. Measures of genetic diversity (uHe, He, Ho, AR) were calculated in GenAlEx, and full-sib groupings were constructed in COLONY. Results suggest that the differentiation between the captive and Northern populations is low (average Zoo population pairwise Fst: 0.014), and measures of genetic diversity were very similar (uHe, He, Ho, AR), indicating that the genetic diversity of the reintroduced hatchling population is representative of genetic diversity in North cluster populations. Linkage disequilibrium-based estimates of effective population size, however, reveal a small genetic effective population size (Ne = 37.2 - 44.6 individuals), which will quickly lead to a loss of genetic diversity. The small effective population size of a single reintroduced cohort and high post-release mortality rates underscore the need for continued annual supplementation to buffer against genetic drift, thereby promoting the long-term survival of managed Texas Horned Lizard populations.

Alkyl phosphate surfactants were synthesized for the development of a dendricore micelle as a potential drug delivery platform. Conventional surfactant micelles often dissociate under physiological dilution due to their high critical micelle concentrations, limiting their utility. To address this limitation, a dendrimer scaffold templated by surfactants is being constructed through reaction of an amine with succinic anhydride followed by iterative Boc deprotection and carbodiimide coupling. This architecture is expected to enhance micelle stability and support dual-drug delivery.