BRCA1 plays an important role in the DNA damage response pathway by promoting the facilitation of homologous recombination with its binding partner, PALB2. Inherited loss of function BRCA1 variants disrupt this highly conserved and stabilized protein-protein interaction, preventing the complex from repairing double stranded breaks in DNA. Hereditary breast cancers have been treated using well-established methods, such as PARP inhibitors and DNA damaging agents. However, nonhereditary breast cancers that retain BRCA1 function are not susceptible to these treatments because they are able to effectively repair their DNA, leading to a proliferation of the cancer cells.
Here, we investigate whether small peptide-mimicking molecules, such as stapled peptides and macrocycles, have the ability to disrupt the BRCA1 and PALB2 interactions. We designed a short sequence of amino acids that mimicked BRCA1’s coiled coil region, the area that binds to PALB2. This sequence was then “stapled” with a short hydrocarbon to create a stapled peptide. The macrocycles were designed by targeting amino acids necessary to the BRCA1/PALB2 interaction. Binding interactions between the peptide mimics and PALB2 were measured using isothermal titration calorimetry (ITC). This method is incredibly reliable for sensing the heat changes upon binding to predict protein interactions. Our results suggest that macrocycles do not inhibit the BRCA1/PALB2 interaction, while the stapled peptides may be competing with BRCA1 for the binding site of PALB2.
Our findings indicate that due to the high specificity and conservation of the BRCA1/PALB2 interaction, finding a molecule to completely disrupt this interaction would require high throughput screening methods to test multiple compounds at once. These proteins may not be susceptible to rational drug design, so testing a variety of compounds may be the best way to disrupt this interaction. Further refinement of the peptide length, sequence, staple placement, and staple chemistry, as well as different macrocycles, may also be useful to effectively inhibit this interaction. Targeting the BRCA1-PALB2 interaction remains a promising strategy for treatment of non-hereditary breast cancers.

Developing Effective Husbandry Protocols for Larinoides
Reliable laboratory husbandry is essential for maintaining healthy spider populations used in ecological, physiological, and behavioral research. However, standardized protocols remain limited, particularly in spiderlings. This project focused on developing and refining husbandry techniques to optimize spider survival, health, and rearing of young under lab conditions. This study establishes and evaluates husbandry protocols for Larinoides orb weavers (Family Araneidae), a group of riparian spiders known for constructing vertical orb webs and their ecological role as important predators in aquatic-terrestrial food webs. Six adult spiders were collected from the Trinity river in Fort Worth, TX and mated in the laboratory. Their spider hatchlings were maintained in individually prepared vials containing artificial vegetation designed to support web attachment and movement. Feeding regiments using immobilized fruit flies and hydration strategies using a diluted honey solution were implemented. Observations of survival, activity, and general health were recorded. The husbandry system promoted consistent housing and care routines to promote spider survival in a laboratory setting. The methods used provided a reproducible system that consistently allowed spiders to successfully mate, reproduce, and nurse spiders to adulthood. These findings will contribute to the rapidly expanding field of spider husbandry by providing a reproducible husbandry system.

BRCA1, a tumor suppressor protein, when dysregulated, leads to a significant proportion of hereditary breast and ovarian cancers. Better understanding the specific enzymatic functions of BRCA1 and the downstream phenotypic effects is important for advancing cancer research. Because crucial signaling pathways controlled by BRCA1, including nucleosome ubiquitylation, are similarly conserved between humans and Caenohabditis elegans (C.elegans), this organism is a valid model to determine the phenotypic effects of BRC-1, a homolog of BRCA1, when its molecular signaling pathways are altered.
It was previously discovered that wild-type N2 C.elegans, which retains a fully functional BRC-1 protein, mainly display an XX genotype and hermaphrodite phenotype. Conversely, the xoe4 knockout mutant has an absent BRC-1 protein and displays an increased frequency of XO males, presumably due to loss of BRC-1 function in proper meiotic crossover during gamete formation. Yet, it is unknown whether the nucleosome ubiquitylation signaling pathway of BRC-1 directly contributes to successful meiotic crossover and XX hermaphrodites.
We hypothesize that the syb5376 mutant strain, which contains the BRC-1 protein but lacks facilitation of nucleosome ubiquitylation, would exhibit an intermediate phenotype with a male frequency higher than the N2 wild-type strain but lower than the xoe4 knockout strain. To test this hypothesis, we quantified the ratio of male to hermaphrodite progeny and compared male frequencies across all three strains.
Consistent with our hypothesis, the syb mutant illustrated a male frequency that was in between the N2 wild-type and xoe4 knockout strains. This suggests that nucleosome ubiquitylation of BRC-1 mediates successful meiotic crossover, but also contributes to this function either by mediating other protein-protein interactions or ubiquitylation of an alternate substrate.
Ultimately, these findings detail the importance of nucleosome ubiquitylation of BRC-1 in C. elegans, which is useful for determining the importance of nucleosome ubiquitylation of BRCA1 in humans. More broadly, this work advances our understanding of how specific molecular functions of BRCA1 contribute to genomic stability and increase breast and ovarian cancer susceptibility.

The Dreissena polymorpha (zebra mussels) and Dreissena bugensis (quagga mussels) are invasive, freshwater species native to Eastern Europe. Since their introduction to the Great Lakes region of the United States in the 1980s, both dreissenid mussels have quickly expanded throughout inland waterways and caused significant economic impacts and ecological changes. Both zebra and quagga mussels have greatly exceeded the expansion range of predicted models, spreading throughout North America and south into warmer waters including Texas. The mechanism facilitating this expansion is a topic of great interest. Understanding differences between cold-water and warm-water adapted mussels may help us to better predict their spread into Texas. In my project, I investigated the differences in temperature tolerance by analyzing survival rates of adult mussels in varying degrees of water. Furthermore, I analyze differences in spawning of egg and sperm and resultant fertilization success between the two groups. Together, these findings provide insight into the temperature-related survival and reproductive strategies that may enable these mussels to continue expanding beyond their predicted range into warmer freshwater environments.

Zebra mussels are an invasive species known to cause adverse ecological impacts by outcompeting native species, disrupting the food web, and destruction to aquatic habitats. Zebra mussels often aggregate on hard surfaces, clogging pipes, damaging boats and infrastructure, etc., leading to costly economic challenges. As broadcast spawners, they release eggs and sperm into the water column where fertilization and larval development occurs. During this process, the larvae may travel long distances enabling their spread into new locations, including Texas. These early stages of the lifecycle (gametes, larvae) zebra mussels will be most sensitive to external factors and conditions. They may also be the most sensitive to control mechanisms such as copper or bleach treatments. Little is known about exactly how long gametes remain in the water prior to fertilization and how long after spawning are they viable. The objective of this research project is to gain a deeper understanding of Zebra mussel reproduction with a focus on gamete viability. I will assess sperm viability using multiple assays including established procedures such as sperm motility using video analysis, gamete and sperm longevity. We have developed novel a fixed egg assay that allows analysis of sperm binding to eggs without the need for freshly spawned eggs. These assays will allow us to determine how long zebra mussel sperm and eggs are viable after release.

Bacillus anthracis is the bacterial pathogen responsible for the lethal disease anthrax. For the pathogens to cause disease, they must overcome several host defenses including obtaining essential nutrients like iron. Our lab has identified that the dUTPase-1 gene is critical for iron acquisition from hemoglobin in B. anthracis. Normally, dUTPase functions to hydrolyze dUTP into dUMP. This functions to maintain DNA integrity as hydrolysis lowers the concentration of dUTP preventing uracil incorporation. This enzyme has never been linked to iron acquisition before, although in other systems, it has been linked with a secondary role in regulating signaling. Our goal is to determine whether the enzymatic activity, dUTP hydrolysis, is important for iron acquisition from hemoglobin. We hypothesize that dUTPase’s enzymatic activity is not responsible for the iron acquisition phenotype, and that it is through another mechanism. To test this we will introduce amino acid substitutions into two highly conserved residues in the active site using site-directed mutagenesis. This mutation should destroy enzymatic activity which we will confirm using a PCR-based assay. We will then test for iron acquisition ability using our established hemoglobin assay. We are currently working on the construction of our enzymatic mutant and optimizing our hemoglobin to test it once it is completed. This research will help us determine which structural domains are key to the iron acquisition activity of dUTPase and shed light on the secondary function of this enzyme.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects behavior, memory, and overall health and well-being. Although it is the sixth leading cause of death in the United States among people aged 65 and older, there is currently no cure or effective preventive treatment. Multiple risk factors contribute to the development of AD, including aging, genetics, chronic stress, and diet. Increasing evidence suggests that diet is a major modifiable factor influencing disease risk through mechanisms involving systemic inflammation and oxidative stress. Diets high in saturated fats, refined carbs, and sugars typical of the American diet promote lipid buildup, especially in the liver. Excess hepatic lipids can cause fatty liver, metabolic issues, inflammation, and oxidative damage, potentially contributing to AD pathology. To better understand how diet influences these biological pathways, our lab developed two macronutrient and calorie-matched rodent diets: one that models a Mediterranean-style diet (MD) and another representing the typical American diet (TAD). Previous studies in our lab using male and female C57BL/6J wild-type mice examined the effects of these diets over shorter periods. In a three-month dietary exposure study, mice fed the TAD exhibited notably greater hepatic lipid accumulation compared to those fed MD, suggesting early metabolic stress. However, gene expression analyses did not show significant evidence of inflammation or oxidative stress. This suggests the duration might not have been sufficient to detect molecular changes. This study prolonged diet exposure to six months to determine whether extended TAD intake leads to alterations in liver gene expression associated with inflammation and oxidative stress. We examined several inflammatory genes (e.g., TNF-α, Il-1β, and IL-6) and oxidative stress-related genes (e.g.,NRF2, HO-1, and SOD) and found that mice on the TAD showed higher expression of inflammatory and oxidative stress markers than MD-fed mice. Our lab has also previously demonstrated that six-month consumption of the TAD diet leads to AD-related markers such as elevated amyloid-β levels in the brain and the associated decrease in cognitive function. Combined, these results suggest that prolonged exposure to poor dietary conditions encourages inflammatory and oxidative stress signals from the liver, which may help drive AD pathology.

The Texas Horned Lizard (Phrynosoma cornutum) has undergone dramatic population declines across its native range due to habitat loss, invasive species, and predation. As a result, Texas zoos and the Texas Parks and Wildlife Department have been attempting to reintroduce hatchlings of this species into areas where it has become extinct. To support reintroduction, graduate researchers from TCU’s biology program glued harmonic tags onto the backs of the hatchling THL, making them easier to locate in the wild and to determine the most viable areas for reintroduction. The hatchlings, however, still experience high predation, and we often find their tags in the scat of various predators, such as snakes, birds, and small mammals. Previous tracking studies suggest coachwhip snakes (Masticophis flagellum) are a major predator of these lizards. Identifying the primary predators of reintroduced populations is critical for improving hatchling survival and informing conservation strategies. Tissue samples were collected for coachwhips, other potential Texas snake predators, and a few mammals to create and test a coachwhip-specific primer. We extracted DNA from the scat and used the coachwhip-specific genetic marker and a horned lizard-specific primer to screen over 80+ fecal samples with tracking tags collected across multiple THL release sites from the 2024 fall season. The results of this study will be used to determine how common coachwhip predation is at the reintroduction sites and whether management actions can be implemented to reduce predation during the early hatchling stage.

Reproductive success in oviparous reptiles is shaped by both nest environment and post-emergence resource availability. While the abiotic conditions of a reptile’s nest can greatly influence hatching success, post-emergence resource availability affects hatchling survival and growth. Many studies evaluate whether females favor particular nesting sites based on abiotic conditions; however no studies have linked nest site choice with post-emergence resource availability. Understanding this relationship could improve habitat management and enhance survival in Texas horned lizard (Phrynosoma cornutum) reintroduction programs. The species’ strong dietary specialization, particularly the reliance of hatchlings on small native ants (Crematogaster, Dorymyrmex, Pheidole, and Tetramorium spp.), makes it possible to test whether females select nest sites that maximize post-emergence prey availability. During the summers of 2023 and 2024, we located 21 nests of Texas horned lizards at a reintroduction site at Mason Mountain WMA and at a natural population (~42 km away) in central Texas. We compared nest and random sites to assess a female’s ability to select a nest site based on fire ant abundance, native ant abundance, soil moisture, soil compaction, and vegetation structure. Using stepwise model selection, results suggest that horned lizards select nest sites that have low soil compaction, reduced grass cover, and high amounts of hatchling prey. This information will be used to determine if there are suitable nesting areas at reintroduction sites and how to best manage land for optimum horned lizard survival. Release sites with softer soil, less grass, and higher abundance of native ants should be prioritized.

A notable occupational gap exists within the STEM (Science, Technology, Engineering, and Mathematics) field between employed women and men. It is likely to occur around the ages of 10-12, as this is when girls typically start to lose interest in STEM-related activities. The purpose of this study is to investigate the views of fourth- and fifth-grade girls on STEM, careers, and post-secondary education as they participate in the STEMpower After-School Club. Additionally, we aim to determine the students’ baseline STEM identities and their interests in STEM careers following their participation in the STEMpower After-School Club. This study is being conducted by following a group of fourth and fifth-grade girls during a year-long academic after-school program. Our methods include a STEM careers survey.