Medicine and Health Sciences Commons^™

Interrogation Of The Molecular Mechanisms That Finetune Fcεri Signaling And Mast Cell Outcomes, Derek A. Rinaldi

Biomedical Sciences ETDs

FcεRI is the ITAM receptor primarily responsible for the allergic response and immune hypersensitivity diseases such as asthma. Regulation of the strength of both FcεRI signaling, and the resulting outcomes, is accomplished via a complex array of molecular mechanisms whose interactions remain unclear. Here, I explored how the biophysical properties of antigens, crosstalk between FcεRI and integrin signaling and Arf6-mediated control of trafficking and exocytosis tune mast cell outcomes. I first found significant differences in FcεRI aggregation, phosphorylation and granule secretion after crosslinking with the multivalent antigen DNP-BSA or the small, trivalent antigen DF3. I also revealed a bi-directional, Syk-mediated …

Environmental Ozone Exposure, Gestational Health, And The Lung-Placental Axis, Russell Hunter

Biomedical Sciences ETDs

Adverse gestational outcomes of pregnancy are a globally occurring threat to fetomaternal health, with limited clinical prognostic and intervention strategies aside from premature labor induction. Epidemiological data shows strong correlations between gestational exposure to air pollution and the incidence of adverse gestational outcomes. The research presented here was designed to evaluate potential murine models of gestational exposure, as well as quantify maternal cardiovascular damage therein. These studies employ radiotelemetry, echocardiography, single cell RNA-sequencing, and untargeted lipidomic analyses in efforts to study these effects. Results implicate cardiovascular responses to mid-gestational ozone exposure as evidenced by decreased maternal cardiac output and increased …

Synthetic Biology Enabled Modification Of Bone Cells And Impact On Bone Mineral Resorption, Dulce C. Hayes

Biomedical Sciences ETDs

Development of a cell culture based bone model can contribute to biomedical research by producing a reproducible model system that mimics a bone remodeling disorder and reduces the use of animals in research studies. Synthetic biology was used to engineer osteoblast cell lines to alter a key protein in the RANKL pathway in efforts to control the bone remodeling process. Osteoblast cell lines, K7M2 and MC3T3-E1 Subclone 4 were engineered to express osteoprotegerin (OPG) and inhibit OPG expression, respectively. The upregulation of OPG expression was confirmed with Real Time PCR and Quantikine® Immunoassay. To identify the functionality of the engineered …

Investigation Of Orthohantavirus Genetics In Rodent Reservoirs And Clinical Samples, Samuel M Goodfellow

Biomedical Sciences ETDs

Orthohantaviruses are negative-sense, single stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of ~36% and the highest cases occuring in the southwest region. The primary SNV host reservoir is thought to be the western deer mouse, Peromyscus maniculatus, however it has been shown that other rodents can carry different orthohantaviruses. We designed a pan-orthohantavirus detection tool to survey several small mammal populations throughout New …

Determining The Existence And Regulation Of Microlipophagy In Primary Brown And White Adipocytes, Sara C. Arenas De Leon

Biomedical Sciences ETDs

Lipids are one of life’s four main macromolecules and provide essential functions to cells.

The degradation of lipid droplets and mobilization of lipids occurs through lipolysis. Emerging evidence demonstrates evidence of a selective form of autophagy in lipolysis. The process of microlipophagy has only recently been described, and many features of its regulation are still poorly understood. Our recent study showed that inhibiting mammalian target of rapamycin complex 1 (mTORC1) pathway by depletion of Raptor in adipocytes led to an influx of lysosomes and accumulation of lipid droplets within lysosome. Here, we expand on these previous findings. We were able …

Effects Of Acute And Chronic Gut Injury On Secretory Lineage Differentiation, Roger Atanga

Biomedical Sciences ETDs

Acute and chronic injury to the gut has several detrimental consequences. However, dysregulation of secretory lineage cells is a common observation. To model acute gut injury, we use non-fissile uranium bearing dust (UBD), an environmental toxicant prevalent in communities adjacent abandoned uranium mines, majority of which are located in the Southwestern United States. Repeated exposure to environmental toxins and heavy metals has been obscurely linked to intestinal inflammation, increased susceptibility to pathogen-induced diseases, and higher incidences of colorectal cancer. However, there is no molecular evidence that non-fissile uranium can cause damage to the intestinal epithelia. Human colonoids exposed to UBD …

Determining The Existence And Regulation Of Microlipophagy In Primary Brown And White Adipocytes, Sara C. Arenas De Leon

Biomedical Sciences ETDs

Lipids are one of life’s four main macromolecules and provide essential functions to cells, as they serve as building blocks of cellular membranes, mediate cell signaling, and are a critical energy source. Within cells, esterified fatty acids aggregate into lipid droplets in the form of triglycerides, consisting of a neutral lipid core surrounded by a phospholipid monolayer decorated with various proteins.

The degradation of lipid droplets and mobilization of lipids occurs through lipolysis, a process that hydrolyzes a molecule of triglyceride into a glycerol and three fatty acids. Emerging evidence demonstrates the involvement of a selective form of autophagy in …

Neuroinflammatory And Metabolomic Temporal Dynamics From Inhaled Wildfire Smoke With Attenuation Via Pharmacological Intervention, David Scieszka, David Scieszka

Biomedical Sciences ETDs

Wildfire smoke is a global issue affecting nearly all humans on the surface of this Earth. Smoke dispersion from wildfires can span continents and cross oceans with amazing ease. Furthermore, total acres of land burned per year in the United States has roughly doubled since 1980, meaning this issue will persist for an indeterminate amount of time. Exposure to wildfire smoke is hazardous and promotes aging-associated events in the cardiopulmonary systems. Yet long- and short-term effects on the brain remain relatively unknown. From these, it is critically important to understand the neurological impacts from wildfire smoke exposure; to compare these …

Effect Of Ligase I Deficiency On Replication Fork And Chromatin, Seema Khattri Bhandari

Biomedical Sciences ETDs

Half of all the eukaryotic nuclear genome is synthesized as Okazaki fragments on the lagging strand at the replication fork. Okazaki fragment synthesis begins with repeated production of short RNA-DNA primers synthesized by the DNA Polymerase α (Pol α)-primase complex. The primer terminus is recognized by Replication Factor C (RFC) which then loads the sliding clamp protein, proliferating cell nuclear antigen (PCNA), resulting in the recruitment of DNA Polymerase δ (Pol δ) which carries out the gap filling DNA synthesis displacing the 5’ end of the preceding Okazaki fragment which is cleaved by Flap Endonuclease 1 (FEN-1), and ultimately the …