Alzheimer’s Disease (AD), the most common form of dementia, currently impacts almost seven million people in the United States over the age of 65. It is predicted that by 2060 over 13 million people in the United States will be affected by AD, which is why there is a growing demand for treatments. Amyloid ꞵ plaques and phosphorylated tau proteins are both associated with the progression of the AD pathology since they play a role in the disruption of neuronal integrity. These aggregated proteins along with other molecules, such as lipopolysaccharide (LPS), lead to increased inflammation by activating the NFκB pathway. The NFκB pathway controls the production of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNFɑ); however, if it is overactive, it can lead to harmful inflammation.The company P2D Biosciences provides novel compounds designed to reduce inflammation, but the exact mode of action of these compounds is unknown. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) can be utilized to measure cytokine mRNA from BV2 cells that have been pretreated with the drugs and then with LPS. In this project we screened multiple compounds provided by P2D Biosciences to evaluate their use as anti-inflammatory agents to treat AD.

BRCA1 is a tumor suppressor protein that normally acts with its partner, BARD1, to facilitate DNA repair, regulation of the cell cycle, and regulation of gene expression. The Caenorhabditis elegans homologs of BRCA1 and BARD1, BRC-1 and BRD-1, respectively, retain these key functions and thus make C. elegans a suitable model organism for studying the functions of BRCA1. While the functions of BRCA1 and BRC-1 are well characterized, the molecular mechanisms by which these functions are carried out is still unclear. For example, BRCA1 and BRC-1 possess E3 ubiquitin ligase activity towards histone H2A in nucleosomes, but it is unknown how this contributes to tumor suppression. While inherited mutations that disrupt tumor suppression lack E3 ligase activity, they also interfere with other critical molecular functions, such as BARD1 binding. To pinpoint the role of E3 ligase activity, we aim to characterize a mutant construct of BRC-1 in C. elegans that lacks E3 ubiquitin ligase activity towards histone H2A but retains the ability to bind BRD-1. In vitro ubiquitination assays demonstrate that our candidate for this mutant of BRC-1, Trip A, is ligase-dead towards histone H2A in nucleosomes. Co-purification of BRC-1 and BRD-1 in which only BRC-1 contained the histidine tag revealed that BRC-1:BRD-1 binding is retained in the Trip A mutant. While these results demonstrate that Trip A meets in vitro requirements for a ligase-dead mutant, further in vivo experiments are needed to confirm its suitability. If confirmed as a suitable ligase-dead mutant through in vivo experiments, Trip A can be expressed in C. elegans to identify which functions of BRC-1 depend on E3 ubiquitin ligase activity towards histone H2A in nucleosomes.

BRCA1 is a tumor suppressor protein that facilitates DNA damage repair, cell cycle checkpoints, and gene expression in humans. The presence of pathogenic mutations in the BRCA1 protein leads to a predisposition to breast and ovarian cancers in humans; these pathogenic mutations can lead to the dysregulation of enzymatic activity and gene expression. It is hypothesized that enzymatic activity of BRCA1 and its ability to regulate gene expression are linked. The gene expression of estrogen-metabolism genes by BRCA1 is mediated, in-part, by the ability of BRCA1 to facilitate the mono-ubiquitylation of nucleosomes on the H2A histone. Our lab is interested in understanding which DNA damage repair and gene expression functions of BRCA1 rely on mononucleosome ubiquitylation. In Caenorhabditis elegans, the BRCA1 homolog, BRC-1, retains the key functions of BRCA1, making C. elegans a suitable model organism to evaluate which functions of BRCA1 rely on nucleosome ubiquitylation. To explore nucleosome ubiquitylation by BRC-1 in C. elegans, we compare three strains of C. elegans, including a wildtype strain, a complete knockout of BRC-1, and an engineered mutant. This engineered mutant contains two point mutations that alter the ability of BRC-1 to interact with the nucleosome to complete ubiquitylation of the H2A histone. We suggest that our proposed mutant repels BRC-1 from the histone to prevent ubiquitylation, yet retains all other BRC-1 functions. We hypothesize that this will hinder the repression of cyp genes, which code for enzymes that catalyze the process that converts estrogen into various metabolites, some of which are harmful. Overexpression of these genes can lead to the accumulation of harmful estrogen metabolites, which can lead to tumorigenesis in estrogen-metabolizing tissues. To assess this, we compare the expression levels of cyp genes, which are repressed in the wildtype strain containing a functional copy of BRC-1. If mononucleosome ubiquitylation is required for transcriptional repression in C. elegans, in the engineered mutant strain, we expect to see elevated levels of cyp gene expression, as also seen in the complete BRC-1 knockout strain. Through understanding the mono-ubiquitylation of nucleosomes by BRC-1 in C. elegans, we can better interpret the genetic variations of BRCA1 in humans and better inform and treat patients with detrimental BRCA1 mutations.

Mosquitoes are primary vectors in the transmission of many infectious diseases, spreading pathogens through their bites after feeding on infected
hosts. Vector-borne diseases like Zika, chikungunya, and yellow fever, mostly transmitted by mosquitoes, cause over 700,000 deaths each year and
account for 17% of infectious diseases, heavily burdening vulnerable communities and economies. Public perception of mosquito control can significantly shape outbreak outcomes [1]. This project uses a mathematical model to simulate how disease spreads between two regions connected by mosquito migration. The model considers how people’s concern for the environment can influence their support or opposition to mosquito control efforts. Our goal is to explore how these factors shape disease prevalence and to better understand the role of community behavior in outbreak prevention.

Oral health is a critical component of overall well-being, yet many individuals in underserved communities lack access to essential dental care and hygiene resources. The New Smiles Drive is a student-led initiative dedicated to improving oral health education and access to hygiene supplies in the Fort Worth community. Through the TCU Tooth Fairies program, we present at elementary schools, engaging students in interactive lessons on proper brushing and flossing techniques to foster lifelong oral hygiene habits. Additionally, we donate hygiene kits—containing toothbrushes, toothpaste, floss, and a laminated educational card outlining proper brushing steps in both English and Spanish—to Mercy Clinic, which provides medical and dental care to uninsured patients, as well as to local homeless shelters. By combining education with tangible resources, New Smiles Drive aims to promote preventive dental care and address disparities in oral health access.