Master of Science (MS), Wright State University, 2021, Microbiology and Immunology

Cardiomyocytes and macrophages have been found to interact via connexin-43 hemichannels. The role of connexin-43, however, is not fully understood. This study shows that these interactions aid in increasing the membrane potential of cardiomyocytes allowing contraction of the cells. HL-1 cardiomyocytes and RAW 264.7 macrophages in coculture increased expression of connexin-43 compared to cardiomyocytes alone. Co-cultures also increased the fluorescence of Di-8-ANEPPS potentiometric dye indicating an increase in cardiomyocyte membrane potential. Treatment with IL-10 and TGF-beta further increased connexin-43 expression and membrane potential. Treatment with SOCS3 inhibited the effects of TGF-beta and IL-10 while having no effect on its own. Confocal imaging can provide visual evidence of these interactions with image layering, 3D imaging and enhanced color.

Doctor of Nursing Practice, Mount St. Joseph University , 2023, Department of Nursing

In 2022, the MICU at a large acute care facility was responsible for the development of two of the four catheter-associated urinary tract infections (CAUTIs) at this hospital site. Therefore, a quality improvement project was implemented to educate the nursing team and increase urinary catheter bundle compliance in an effort to prevent CAUTIs. Education was developed and implemented which led to an increase in bundle compliance from as high as 96% pre-implementation to 97% post-implementation and a decrease in standardized infection ratio (SIR) to zero in this MICU, despite an increased standardized utilization ratio (SUR) to greater than 1.02 during the post-implementation phase. This project supports other literature that identifies that implementation and compliance of a urinary catheter bundle will lead to CAUTI prevention.

MS, University of Cincinnati, 2021, Medicine: Clinical and Translational Research

Importance: A robust prediction rule exists for clinical investigation of serious or invasive bacterial infection in infants 60 days and younger, but real-time measurement of procalcitonin is necessary for application of this rule. For clinicians unable to apply the existing prediction rule, the significance of leukopenia (WBC count <5000 cells/µL) in identifying SBI and IBI is unclear. Objective: To estimate the probability of SBI and IBI in febrile infants 60 days and younger with leukopenia or neutropenia. Design, Setting, and Participants: Secondary analysis of two combined prospective, observational cohort studies. Convenience samples of febrile infants 60 days and younger were collected at 26 North American emergency departments. Data were analyzed between July 2020 and February 2021. Exposures: Clinical data including age, qualifying fever temperature, and Yale Observation Scale score, as well as laboratory data including WBC count, ANC, urinalysis, and serum procalcitonin (PCT); multivariable logistic regression was performed using these predictors. Main Outcomes and Measures: SBIs, defined as culture-positive urinary tract infection, bacteremia, or bacterial meningitis, and, IBIs, defined as bacteremia or bacterial meningitis. Results: Of 7407 eligible participants, we estimated odds of SBIs and IBIs in 6865 febrile infants 60 days and younger with leukopenia and neutropenia without inclusion of serum PCT levels (complete cohort) and 3098 with serum PCT levels (PCT cohort). We used the commonly accepted WBC count range of 5000-15000 cells/µL as normal reference and found WBC count <2500 cells/µL significantly increased the odds of SBIs (OR 23.77, 95% CI 6.05-74.09, p<0.001) and IBIs (OR 13.48, 95% CI 2.92-45.35, p=0.012) in the complete cohort. This relationship did not hold true for WBC count 2501-5000 cells/µL, nor for any degree of neutropenia, in either the complete or PCT cohorts. Conclusions and Relevance: WBC count <250 (open full item for complete abstract)

Doctor of Philosophy, Case Western Reserve University, 2021, Systems Biology and Bioinformatics

Strategies to find an effective TB vaccine have relied on enhancing the natural immunity that occurs in a subset of the population in response to primary exposure or reinfection with Mycobacterium tuberculosis (Mtb). Although still controversial, there is good evidence that some people exposed to Mtb show early clearance of the infection and do not exhibit a specific T-cell response that is the hallmark of Mtb infection. At the same time, the majority of people who do become infected, never progress to an active TB state and remain healthy without symptoms for many years. New vaccine candidates will require better targeting of these natural mechanisms through increased knowledge of immune functions. The biological processes contributing to early clearance of infection can be investigated by comparing individuals who resist infection to those with stable latent infection. We compared lung and blood cell subsets in a Ugandan cohort and found subtle differences that may contribute to resistance. In addition, we were able to quantify lymphocyte memory cell populations in the lung and blood and found a greater percentage of effector memory cells in the lung. Recent vaccine candidates have induced a robust T-cell response to Mtb antigens as measured in the blood, and yet provide no significant protection against progression from infection to disease. One hypothesis is that measurement of vaccine biomarkers in the blood do not correlate with markers in the lung where infection occurs. In this study, proteomic profiles in alveolar macrophages and blood monocytes were measured to answer the question of whether there is a differential IFN-γ cytokine response in these compartments. We found greater overall protein expression in monocytes that was not explained by differences in proximal signal transduction. In order to further interrogate IFN-γ transcriptional processes, we performed a meta-analysis with MDM transcriptomic datasets and combined the results with STAT1 tra (open full item for complete abstract)

Bachelor of Science (BS), Ohio University, 2019, Biological Sciences

Staphylococcus aureus is classified as a major pathogen due to the number of diseases it causes and that infections caused by S. aureus are notoriously difficult to treat. One reason for this difficulty is that these infections are frequently recurrent in nature. Previous studies have demonstrated that patients are often re-infected with their original infecting strain of S. aureus suggesting that the applied antibiotic treatment failed to eliminate the original infection in the first place. A potential reason for this phenomenon is attributed to how S. aureus lives in the body particularly inside human cells. Infection of human cells and intracellular persistence enables S. aureus to evade the immune system and avoid applied antibiotic treatments. This form of growth effectively acts as an intracellular reservoir of S. aureus which can be re-released back into the extracellular environment to cause recurrent infections. This project aimed to increase our understanding of how S. aureus adapts and persists inside non-professional phagocytic and professional phagocytic cells in both initial and late stages of infection. This was accomplished by developing model intracellular infection conditions and by using them to identify transcriptomic alterations and genetic factors that play a role in intracellular survival and persistence. These identified transcriptomic alterations and genetic factors can be used as future potential therapeutic targets to eliminate intracellular S. aureus reservoirs and a key method of recurrent infection by S. aureus.

Doctor of Philosophy, The Ohio State University, 2018, Biomedical Sciences

P. aeruginosa is one of the most common causes of nosocomial infection and is frequently the cause of lethal lung and wound infections. These infections are often difficult to treat due to the formation of aggregated communities, known as biofilms. The process of biofilm formation is complex and involves the production and secretion of a protective extracellular matrix. Once encased in the biofilm, P. aerguinosa becomes more tolerant to killing by antimicrobials, host immune factors, and other environmental stressors. Thus, these infections are often difficult to treat and frequently lead to chronic infection. A major component of the biofilm matrix is the exopolysaccharide (ePS) Psl. This exopolysaccharide provides structural support for the biofilm and aids in cell-cell and cell-surface attachment. Additionally, Psl protects bacteria and promotes drug tolerance by sequestering antimicrobials and immune components before they reach the active bacterial population. Over the course of infection, P. aeruginosa adapts to the host environment leading to mutations which promote survival. Strains with mutations causing overproduction of the ePS, Psl and Pel, are frequently isolated from chronic infection. These hyperbiofilm forming strains have been named rugose small colony variants (RSCVs), and their presence has been correlated to poor prognosis. A positive selective pressure for RSCVs exemplifies the importance of Psl during infection, but it was unclear specifically what ePS overproduction does during infection. Here, we describe how Psl overproduction negatively effects the host. Considering these effects, we then sought to 1) target Psl directly with therapeutics and 2) identify novel Psl regulators to provide new targets for disrupting synthesis. We report that the overproduction of Psl by RSCVs leads to auto-aggregation and inflammation in the lung. The clustering of bacterial cells promotes host recognition resulting in ROS and pro-inflammatory cytokine (open full item for complete abstract)

MS, Kent State University, 2016, College of Architecture and Environmental Design

Transmission of airborne diseases in healthcare facilities is an increasingly important concern. This, in part, is due to the reduction in funding from insurance companies for hospital-acquired infections (HAI) and the consequent economic impact of an influenza outbreak in a hospital. With recent cases of HAI in the USA, it became necessary to examine the current ventilation standards for healthcare facilities. Among the organizations that set standards for the prevention of disease transmission are Facilities Guidelines Institution and the American Society of Heating Refrigeration and Air-Conditioning Engineers (ASHRAE). These standards have played an important role containing airborne transmitted diseases such as Influenza A in North American hospitals. While, design guidelines have focused on recommending appropriate ventilation rates, it ignored the delivery of conditioned air to occupied spaces and the impact of room layout relative to the placement of air supply and return. Airflow is often designed to contribute positively to air-mixing and distribution, improvement of thermal comfort and air quality conditions. Unfortunately, air distribution contributes to airborne pathogen transmission as well. Few studies focused on the relative location of air supply and as well as the impact of the movement of people, but none found focused on the patient room design and layout relative to recommended airflow patterns. This research focuses on a development of a guideline to help designers understand the effect of room design on the distribution of airborne diseases and the Influenza virus in particular. The paper will present the outcomes of several Computational Fluid Dynamic (CFD) simulations of typical room configurations and layouts under many room use scenarios. The model used for simulation is calibrated and verified by field measurements of air distribution patterns in patient rooms. In addition to airflow patterns, the CFD algorithm is used to determine the (open full item for complete abstract)

PHD, Kent State University, 2007, College of Biomedical Sciences

To study early events of neonatal Herpes Simplex Virus (HSV) encephalitis and its sequelae we induced a controlled infection in the brains of mice using HSVgH-, a genetically modified Disabled Infective Single Cycle virus. Neonatal Balb/C mice were infected with various amounts of HSVgH- virus by intracerebral injection. Results showed that the survival of infected mice was dependent on the amount of virus injected. Infection with 200,000 plaque forming units (pfu) of HSVgH- virus resulted in 0% survival, whereas 25,000 pfu resulted in 75% survival. If the mice died, 98% of the deaths occurred between 3 and 7 days after infection. Replication competent virus was recovered from 20% of mice brains infected with 25,000 pfu of HSVgH-. Neutralizing antibodies were not detected 6 weeks post infection in sera of mice, which survived infection with 25,000 pfu of HSVgH-. LacZ histochemistry and immunoperoxidase staining using anti-HSV and anti-beta-galactosidase antibody revealed that the infection was limited to the site of injection. Tissue destruction was observed at the site of inoculation 3 days post infection using cresyl violet staining. At 3 days post infection adjacent sections showed positive cells for viral antigens and apoptotic cells in the infected area. Immunoperoxidase staining using antibodies to surface markers showed microglial activation beginning on day 1 and astrocyte proliferation beginning on day 3-post infection. B and T lymphocytes were not detected on day 1 through 7-post infection. This controlled experimental HSV infection suggests a limited non-specific early host response of innate immunity and absence of adaptive immunity in the neonate to HSV encephalitis.

Doctor of Nursing Practice Degree Program in Population Health Leadership DNP, Xavier University, 2025, Nursing

New onset traumatic spinal cord injuries are detrimental to individual patients as bodily autonomy is heavily impacted after the cord is damaged. The population is vulnerable as the anatomical and physiological presentations are highly compromised, requiring attentive nursing care. Patients experience dysregulation between vital organ systems, which can cause bladder, bowel, and skin complications. The lack of education protocols was problematic, causing a confidence and knowledge deficit in nurses. The purpose of the evidence-based practice project was to enhance education in the hospital setting to prepare patients with spinal cord injuries for safe discharge through three phases. Phase one aimed to improve nurses' confidence and knowledge of the spinal cord and provide individualized care plans for the bladder, bowel, and skin to reduce urinary tract infections, severe fecal complications, and pressure injuries. Phase two addressed patients, families, and caregivers in the inpatient setting to improve bladder, bowel, and skin management. The goal was also to enhance self-efficacy and quality of life by measuring four validated tools. Phase three was planned to follow up with patients post-discharge to assess training, measure any incidences of adverse events, and conduct the four validated tools again. Phase one was conducted through a standardized 60-minute training program with pre-testing, education, and post-testing. Results provided increased nurse knowledge and confidence in bladder, bowel, and skin care programs. No patients were admitted during the initial implementation window for phase two. Additional follow-up will be provided for phases two and three. Individualized and collaborative management strategies are imperative to assist patients with managing bladder, bowel, and skin programs.

Doctor of Nursing Practice, Mount St. Joseph University , 2025, Department of Nursing

Unplanned perioperative hypothermia occurs when a patient's body temperature drops below 36°C / 96.8°F during the perioperative period. Patients who experience unplanned perioperative hypothermia are at increased risk of multiple complications. While investigating a rise in surgical site infections at a hospital in southwest Ohio, it was discovered that perioperative patients were sustaining unplanned perioperative hypothermia throughout their entire procedure. After consultation with key team members, the absence of a warming protocol was identified as the barrier to maintaining normothermia. A literature review was conducted, and evidence was gathered, appraised, and synthesized. Based on the findings and team member suggestions, a warming protocol was developed and implemented. The protocol focused on initiating forced-air warming preoperatively and maintaining warming methods intraoperatively on surgical patients undergoing general or spinal anesthesia. During the three-month implementation period, the project impacted a total of 1,383 patients and resulted in a 32% reduction in patients sustaining unplanned perioperative hypothermia intraoperatively. Additionally, the project also noted a 31% reduction in reported surgical site infections during the implementation period. This evidence-based quality improvement project highlights the importance of implementing evidence-based practice for positive patient and organizational outcomes.

Master of Science, The Ohio State University, 2025, Immunology and Microbial Pathogenesis

Monocytes play a critical role in HIV infection, mediating immune dysregulation through persistent inflammation and as viral reservoirs. This study focuses on the relationship between monocyte dynamics and markers of inflammation and gut integrity in HIV patients before and after antiretroviral therapy (ART). Using high-dimensional flow cytometry of peripheral blood monocytes and plasma biomarker analysis, we investigated alterations in peripheral blood monocyte populations and plasma biomarkers of inflammation and gut microbial translocation in ART-naive and long-term ART-treated individuals. We observed significant shifts in monocyte phenotypic clusters between pre- and post-ART PBMC samples. Additionally, we saw pronounced increases in biomarkers of inflammation and gut integrity between pre- and post-ART plasma samples. Moreover, we observed correlations between monocyte clusters and plasma markers of immune dysregulation, suggesting relationships between specific monocyte clusters and comorbidities associated with long-term ART-suppressed HIV. In pre-ART patients, we found cluster-specific correlations between clusters 2, 6, and 8, and biomarkers IFAB (intestinal fatty acid binding protein) and TNFR-II (tumor necrosis factor receptor II), suggesting associations with gut inflammation markers during early, untreated HIV. Post-ART results showed roles for cluster 1 and ox-LDL, implicating it in cardiovascular conditions. Distinctly, we saw a negative correlation between cluster 5 and IFAB, suggesting a role in the modulation of gut dysregulation. This comprehensive analysis underscores the heterogeneity of monocytes and their critical role in HIV pathogenesis and ART-associated comorbidities. These findings provide promising avenues for targeting monocyte subsets to help mitigate immune activation and lessen its impact on gut dysregulation and cardiovascular risk in PLWH undergoing long-term ART.

PhD, University of Cincinnati, 2024, Arts and Sciences: Biological Sciences

The Brush-legged wolf spider, Schizocosa ocreata (Hentz, 1844), is a well-studied invertebrate model species, with a background of behavioral research on sexual selection, mating, and reproduction. Previous studies have tested the effects of bacterial infection on S. ocreata, using the common arthropod pathogen Pseudomonas aeruginosa - and found that infection resulted in altered male morphology and behavior, and reduced mating success of males. This dissertation examined the influence of infection stress on mating behavior and reproductive success of both male and female S. ocreata, exploring several areas related to stress/potential immune function trade-offs. I tested the hypothesis that infection will confer negative fitness consequences in several contexts, and that there is potential for sexually dimorphic responses to infection due to life history constraints arising from unequal parental investment. Through experimental infection with P. aeruginosa, I examined potential trade-offs in several contexts related to mating and fitness. I found that females respond to infected males with aggression, however, if there is only one male available, infection does not necessarily preclude whether mating occurs. When given a choice, control females show preference for mating with control males while infected females do not, and control males show significantly higher courtship rate toward control females compared to infected females. Still, when testing female preference for high quality male stimuli in different sensory modes, control females showed a strong preference only for high-quality visual stimuli, while infected females showed reduced preference, suggesting a fitness consequence for females brought about by infection. Furthermore, males can detect active infection through female dragline silk alone and modulate their courtship investment based on female infection status. Beyond mating behavior, locomotor endurance and performance depend on the age of t (open full item for complete abstract)

Master of Science, The Ohio State University, 2008, Graduate School

Doctor of Philosophy, Case Western Reserve University, 2024, Epidemiology and Biostatistics

Tuberculosis (TB) continues to be a major public health problem globally. In 2022, TB was responsible for over 1.3 million deaths. One of the World Health Organization's (WHO) End TB Strategy goals is to reduce the incidence and mortality of TB by identifying those who are at the highest risk of developing TB and promptly treating them. Recently, the focus of research has turned to converters or individuals who have acquired Mtb within the past two years (acute Mtb infection). These converters have the highest risk for disease progression and being able to identify them before they develop TB and become contagious would be a crucial step in achieving the elimination of this disease. The only diagnostic tools available to identify converters, the tuberculin skin test (TST) and interferon gamma release assay (IGRA), have several limitations. The objective of this project is to identify factors associated with conversion of both the TST and/or IGRA, examine whether quantitative TST and/or IGRA measures further clarify differences, and to evaluate whether these factors are also associated with progression to incident TB. This project is one of the few in the world that collects both IGRA and TST on household contacts of TB cases, providing a unique opportunity to examine both diagnostic tests together. This question is critical as many TB research studies globally are transitioning to the exclusive use of IGRA. A clear definition of conversion would be necessary to obtain more meaningful results from research that targets those individuals at higher risk for progression to TB. It would also be an important step in improving the effectiveness of preventive therapy.

PhD, University of Cincinnati, 2024, Medicine: Immunology

The immune and hemostatic systems are evolutionarily linked in their cooperative defense of the host. While many studies link hemostatic and innate immune regulation, the contribution of hemostatic components to adaptive immune responses have been under studied. Here we explored the capacity of the central hemostatic protease, (pro)thrombin, in regulating the response of cytotoxic CD8+ T cells during cancer and viral infection. We show a novel role of thrombin in supporting adaptive immune anti-tumor responses upon PD-1 blockade therapy. Similar findings uncovered tumor-derived tissue factor as a likely source of thrombin generation in the tumor microenvironment. Our in vivo and in vitro findings suggest that thrombin can enhance CD8+ T cell effector functions in a PAR-1 independent fashion. However, our data also suggests that thrombin-mediated cleavage of PAR-1 leads to transactivation of PAR-2, which acts to limit CD8+ T cell functions. Consistent with this, our data show that PAR-2 deletion or inhibition can enhance CD8+ tumor infiltrating lymphocyte (TIL) anti-tumor responses during aPD1 therapy. We hypothesize that further investigation into combination therapies utilizing CD8+ T cell specific PAR-2 inhibition with PD1 blockade could result in effective tumor clearance. We discovered a requirement of (pro)thrombin in protecting against fatal T cell-mediated anemia during chronic LCMV infection. We depleted circulating prothrombin to 10% of normal levels in mice prior to infection with a high dose of the clone 13 strain of lymphocytic choriomeningitis virus (LCMV). This virus is non-cytolytic, so any pathology and mortality are consequences of antiviral T cell activity. Surprisingly, lowering prothrombin levels resulted in 100% mortality following infection with this normally non-lethal dose of LCMV. Depletion of CD8+ T cells prevented this mortality. Yet, no known mechanism of T cell response to high dose LCMV, including exacerbated cytokine p (open full item for complete abstract)

PhD, University of Cincinnati, 2024, Medicine: Immunology

Natural killer (NK) cells are a subset of innate lymphocytes characterized by their ability to eliminate infected or non-self cells. In addition, NK cells play a noncanonical role in regulation of adaptive immune responses. After certain viral infections and vaccinations, NK cells kill a subset of activated T cells in a perforin-dependent manner. The clearance of these T cells early in the immune response negatively affects downstream antiviral immunity. Ergo, NK cell suppression of adaptive immunity dictates the outcome of viral infections and efficacy of vaccinations. However, the mechanisms driving immunoregulatory activity of NK cells remain incompletely defined. The established requirement for perforin in NK cell immunoregulation suggests the necessity for cell-to-cell contact between NK cells and their targets. At homeostasis, NK cells and T cells localize in different tissue compartments. Chapter II explores re-localization of NK cells to T-cell rich sites after infection, a phenomenon shown to be dependent on the dose of virus given. This is shown to be associated with reduced induction of type I interferons during the lower doses of virus, which limits upregulation of the necessary chemokine ligands involved in NK cell enrichment within T cell rich regions of lymphoid tissues. Localization of NK cells and subsequent regulation of T cells is dictated by the pattern of type I interferon expression. However, pleiotropic effects of interferon on NK cells, T cells, and other immune cells precluded clear dissection of the precise dose-dependent governance of NK-cell immunoregulatory capacity. Cell transfer experiments complement current strategies to study NK cell immunoregulation but are predominantly used in anti-tumor models or in mice with incomplete immune systems. The conventional need for proliferative expansion of NK cells in a less competitive, immunodeficient environment when performing adoptive transfer studies precludes use of such models to e (open full item for complete abstract)

Master of Science, Miami University, 2024, Biology

Lyme disease, caused by the bacterium Borrelia burgdorferi , is transmitted to humans through ticks, and it has become an increasing problem in the Midwest. In recent years, cases have been expanding from a hotspot in Wisconsin to Michigan's Lower Peninsula (LP) along the coastline of Lake Michigan. The expansion of cases coincides with increasing populations of deer tick, Ixodes scapularis , and of the white-footed mouse, Peromyscus leucopus , which serves as the primary reservoir host for the bacterium. A study from 2010 testing the infection prevalence in both deer ticks and white-footed mice found no infections in either species in most of the northern LP. For this study, mice were trapped along a transect from the edge of the known range of infected mice northeastwards toward the tip of the LP. Infected mice and ticks were found more than 100km beyond the previous limit but were not found along the eastern part of the transect. The proportion of P. leucopus carrying ticks was correlated with higher infection prevalence in both ticks and mice.

Doctor of Philosophy, The Ohio State University, 2024, Biomedical Sciences

Severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) infected, asymptomatic individuals are an important contributor to Coronavirus Disease 2019 (COVID-19) transmission. SARS-CoV-2-specific immunoglobulin (Ig)—as generated by the immune system following infection or vaccination—has helped limit SARS-CoV-2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID-19 incidence and SARS-CoV-2 lineage, viral load, saliva Ig levels (SARS-CoV-2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in asymptomatic individuals between January 2021 and May 2022. These data were generated as part of a large university COVID-19 monitoring program in Ohio, United States of America, and demonstrate that COVID-19 incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva SARS-CoV-2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each SARS-CoV-2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA, and IgG responses, the latter increasing significantly post-infection and being more pronounced than Nucleocapsid-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees' saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data are consistent with COVID-19 vaccines having achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Sp (open full item for complete abstract)

Doctor of Philosophy, Case Western Reserve University, 2024, Molecular Medicine

Understanding the viral infection and lifecycle of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) and Kaposi's Sarcoma-Associated Herpesvirus (KSHV) is important in improving disease outcomes and reducing viral prevalence. In our SFTSV study, we discovered specific cytokine profiles associated with the severity of clinical symptoms. We used single cell RNA sequencing (scRNAseq) on patient blood samples to identify a unique expansion of the B cell population in SFTSV-induced fatal cases which indicated that plasma B cells are a primary reservoir of SFSTV replication. These findings present a potential method of reducing the severity of SFTSV infection, especially in aged patients who are more susceptible to adverse outcomes. In our KSHV study, we developed a novel oral 3D infection model and demonstrated that KSHV can only infect exposed basal epithelial cells in the oral epithelia. We used scRNAseq to show that keratinocyte differentiation and cell death pathways were affected by KSHV infection, suggesting that epithelial differentiation could contribute to KSHV reactivation through changes in epigenetic regulation. In addition, we found a unique population of infected cells with limited early lytic gene expression and a unique gene expression profile, which we termed latent-2 cells. These findings demonstrate that our in vitro 3D epithelial ALI culture model should be a valuable tool to further understand oral KSHV infection for the development of future anti-viral therapeutics to block KSHV transmission.

Master of Sciences (Engineering), Case Western Reserve University, 2024, Biomedical Engineering

Healthcare associated infections (HAIs) in the United States cost $28.4 to $33.8 billion a year and 25.6% of HAIs come from the use of medical devices. There is a need for a strategy to decrease infection rates to prevent further surgeries in patients. An electrosprayed polymerized cyclodextrin (pCD) coating of crosslinked polymer can provide affinity-based release Minocycline that prolongs its efficacy. The parameters of the electrospraying solution and process were tailored to provide spherical droplets. Spherical droplets were fabricated in multiple different formulations through SEM analysis and ATR-FTIR confirmed the success of crosslinking. The drug loading and release study did not have the expected results. Through further analysis it was shown that the coating was not strongly adhered to the stainless steel. Therefore, future work is proposed on surface modification and functionalization to create a stronger bond between the polymer coating and the stainless steel surface.