Other Medicine and Health Sciences Commons^™

Targeting Myeloid Cell Iron Metabolism In Salmonella-Induced Colitis, Mariella Arcos Padilla

Biomedical Engineering ETDs

Salmonellosis is a severe infection caused by Salmonella enterica serovar Typhimurium, leading to significant global morbidity and mortality.

Previous studies have shown that mice lacking the iron storage protein ferritin heavy chain (FTH1) in myeloid cells exhibit worsened Salmonella infection. Nuclear receptor co-activator 4 (NCOA4) directs FTH1 autophagic degradation to release iron from storage during conditions of low iron. However, the role of myeloid NCOA4 in regulating bacterial infections remains unclear.

Here, we found that myeloid NCOA4 deficiency augments spleen iron levels and increases cellular iron accumulation, oxidative stress, and ferroptosis in bone marrow-derived macrophages (BMDM) cells. This deficiency also …

Formulation, Characterization, And In Vivo Immunogenicity Evaluation Of Heat-Stabilized Dissolvable Polymeric Microneedles, Aidan Lane Leyba

Biomedical Engineering ETDs

Since its introduction, vaccination has improved health outcomes tremendously. However, modern vaccination efforts are still difficult to implement, particularly in developing countries with warm climates. This includes complex and expensive cold-chain management of vaccines to maintain stability, a lack of medical personnel to administer parental vaccines, and needle phobia. As an alternative, dissolvable microneedles have recently been studied for their simple and painless application. In this thesis, I present a novel manufacturing process for polymer-based dissolvable microneedles, loaded with virus-like particles vaccines conjugated to TRIO or Sialokinin peptides to target malaria and arboviruses, respectively. We have performed multiple characterization studies …

Heterochiral Dna Nanotechnology For Biomedical Applications, Tracy L. Mallette

Biomedical Engineering ETDs

In the past 30 years, there have been major advancements on how to treat and diagnose disease because of the improvement and increase in accessibility of sequencing technology. Nucleic acid-based therapeutics can manipulate protein expression. Likewise, pathogens can be identified and detected with single nucleotide specificity. However, the underlying oligonucleotide technology requires protection against natural defense systems that have evolved to destroy foreign nucleic acids. Many chemical modifications that can protect nucleotides also have significant cytotoxic side effects and must be carefully designed into the strands. A novel way to protect against nuclease-mediated degradation is through the use of mirror-image, …

Spatial Single-Cell Identification Of Cell Layers Within Mouse Brain Using A Novel Spatially Resolved Transcriptomics Technology, Radha Swaminathan

Biomedical Engineering ETDs

Spatially resolved transcriptomics technologies investigate gene expression in the context of a tissue. While imaging-based technologies enable gene expression quantification at a single-cell level, only two NGS-based technologies are currently capable of single-cell resolution. Both Stereo-seq and Seq-Scope involve two rounds of sequencing: one to sequence the location of spatial barcodes and the other to obtain sequence of cDNA. Thus, the objective of the research study is to develop a technology that can capture transcripts from every cell of a tissue without the need for two rounds of sequencing. To this end, a capture surface or barcoded array (similar to …

Development Of A Programmable, Open-Source, And Cost-Effective Fluidic System For Cell Culture Applications, Charles Montoya

Biomedical Engineering ETDs

Open-source laboratory equipment has become an increasingly popular alternative to commercially available options due to its simple implementation, capability of user-customized modifications, and cost-effectiveness. Presented here is the development of a programmable and open-source fluidic system comprised of three custom-built syringe pumps for cell culture applications. The fluidic system was directly integrated with a multiwell plate on an environmentally controlled microscope platform for live-cell imaging and time-lapse analyses of cellular responses as culture conditions are adjusted using the programmable fluidic system. Proof-of-concept of this system is obtained by controlling autophagic activity in A549 cells by adjustment of nutrient supply. The …

Surgical Intervention With Adjunctive Cryotherapy For Canine Conjunctival Hemangiosarcomas Versus Hemangiomas, Lisa M. Hoard

Biomedical Engineering ETDs

Conjunctival hemangiomas and hemangiosarcomas are vascular tumors that affect the tissue in the eyes of canines. While relatively rare, these tumors can be costly to remove, and have a possibility of recurrence. Therefore, more understanding of the nature of these tumors and recurrence rates is of importance to the veterinary ophthalmologist. To date, there is limited data in the literature (2 retrospective studies) that examine the development, treatment, and recurrence of these vascular tumors; furthermore, the analyses do not examine the potential recurrence of tumors after treatment with therapies adjunctive to surgery (such as cryoablation, radiotherapy, and others). For this …

Fumarate-Based Polymers: Oligo(Poly(Ethylene Glycol) Fumarate) And Poly(Butylene Fumarate) For Tissue Engineering Heart Valve And Bone Tissue, Christian T. Denny

Biomedical Engineering ETDs

Tissue engineering is an emerging field that came from the fields of medicine, materials science, and engineering. The foundation of tissue engineering uses a paradigm that incorporates cells, biomaterials, and exogenous factors to create living tissues for medical, pharmaceutical, and research purposes. Within the last 100 years, biomaterials have been developed to solve many medical and research problems. As biomaterials have developed throughout the years new materials have been developed to have specific properties appropriate for medical applications. Fumarate is a naturally derived molecule in the body and has been found useful for developing polyesters that can be crosslinked into …

The Development Of An Instrument To Measure Transdermal Hydrogen Sulfide As A Way To Evaluate Microvascular Health In Humans, Benjamin Thomas Matheson

Biomedical Engineering ETDs

Hydrogen sulfide (H₂S) is a gasotransmitter critical in maintaining microcirculation homeostasis. Impaired microcirculation occurs in multiple disease states such as peripheral vascular disease, diabetes mellitus (DM), and hypertension. Early detection and identification of patients with DM who are at risk for heart attack, stroke and amputation due to microvascular disease is crucial. Human skin is an accessible vascular bed that provides an opportunity to non-invasively measure H₂S, which could be used as a biomarker to evaluate microvascular health.

In this work, a novel H₂S gas sensor, called the transdermal arterial gasotransmitter sensor (TAGS^{TM …}

Screening And Characterization Of A Pan-Gtpase Inhibitor, Leyla Akhadov

Biomedical Engineering ETDs

Abnormal functioning of small GTPases is implicated in a variety of diseases, ranging from neurological and developmental diseases to cancer. In fact, mutant GTPases are found in up to 30% of cancers. Thus, small GTPases are a highly relevant target in drug discovery and development. High-throughput targeted screening of small molecules is the most productive method of discovering compounds that can give insights into drug development. This thesis describes improvements made to a high-throughput GTPase-targeted screening method to minimize confounding systematic error. It also describes the follow-up characterization of a compound that was identified in a high-throughput screen. The compound …

Incorporation Of Egfr And Ron Receptors Into Nanodiscs, Cristina Flores-Cadengo

Biomedical Engineering ETDs

Understanding the structure-function relationship of membrane receptors is essential to comprehend the crosstalk between key signaling pathways. Aberrant trans-activation between receptors can lead to tumorigenesis. Two of these receptors known to be involved in cancer development are receptor tyrosine kinases (RTKs), RON (Recepteur d'Origine Nantais) and EGFR (Epidermal Growth Factor Receptor). There has been evidence of heterodimerization and crosstalk between these two receptors based on co-immunoprecipitation, however the structural requirements behind these interactions remain unknown. Structural studies could provide insights into these RTKs’ modes of dimerization and structure-function relationship. However, structural studies of full-length membrane proteins are often difficult due …

Effect Of Strong Electrolyte Containing Gelling Aids On The Sol-Gel Transition Temperature Of Hypromellose 2910, Elnaz Sadeghi

Biomedical Engineering ETDs

Hypromellose, or hydroxypropyl methylcellulose (HPMC) - has been widely used for biomedical and pharmaceutical applications due to its advantages, including that it is modifiable in terms of viscosity, and it has the ability to form thermally reversible hydrogels. The thermal gelation temperature (T_Gel) of a given HPMC solution strongly depends on its characteristic grade and the solution concentration. Applying certain additives can modify the T_Gel even further; depending on their nature and concentration. With the addition of said additives, a lower or higher T_Gel can be obtained. For example, the addition of sodium chloride (NaCl) reduces …

Housing Condition Impact On Pae Learning And Bdnf Expression., Annette K. Fernandez Oropeza

Biomedical Engineering ETDs

Prenatal alcohol and early life stress exposure are associated with reduced levels of BDNF in the frontal cortex. Several studies have implicated (BDNF) in frontal cortex as important contributor of learning and memory. In the present study, we look to determine whether early housing conditions could mitigate the impact of prenatal alcohol exposure on learning as well as BDNF expression in sex-specific manner in frontal cortex of mice. Compared to control, prenatal alcohol mice expresses reduced total BDNF levels and displayed reduced freezing behavior response during contextual fear conditioning in both female and male mice. Female displayed increased BDNF levels …

Acoustofluidics And Soft Materials Interfaces For Biomedical Applications, Frank A. Fencl

Biomedical Engineering ETDs

This dissertation describes fabrication of devices and other tools for biomedical applications through the integration of acoustofluidic systems with bio separation assays, instrumentation components, and soft materials interfaces. For example, we engineer a new class of transparent acoustic flow chambers ideal for optical interrogation. We demonstrate efficacy of these devices by enhancing the signal for high throughput acoustic flow cytometry, capable of robust particle focusing across multiple parallel flowing streams. We also investigate an automated sampling system to determine the parameters of transient particle stream focusing in between sample boluses and air bubbles to model a high throughput, multi-sampling acoustic …

Next Generation Sequencing Technologies For Real-Time Genotyping And Targeted Sequencing For Precision Medicine, Priyanka Rawat

Biomedical Engineering ETDs

Astounding success of Human genome project and accelerating success of sequencing technologies have enabled $ 1000 genome goals possible. But, this is still far-fetched from the reach of many resource refrained populations with high genetic variations causing lethal genetic diseases. Based on present technology principles, I have developed prototypes for affordable, scalable and customizable point-of-care genotyping and targeted sequencing. Ion-sensitive field effect transistors with novel read-out and signal amplification techniques are used for laying foundation of possible ISFET based allele-arrays. Sequencing-by-synthesis based full-fledge sequencer is made with novel immobilization, flow-cell and data acquisition methods for massive sequenciing.

Mathematical Modeling For Predicting Chemotherapy And Nanoparticle Treatment Efficacy In Breast Cancer, Terisse Arielle Brocato

Biomedical Engineering ETDs

Breast cancer treatment response varies by subtype, treatment regiment, and additionally by vasculature characteristics. For this reason, breast cancer is a model disease for the development of both targeted therapy and prognostic and predictive biomarkers. Mathematical modeling allows for personalized patient specific prediction of treatment outcome based on parameters found to be important to the cancer type. Mathematical modeling is beneficial in providing insight into why cancer treatment fails and in what cases, additionally determining what characteristics result in a successful treatment. Presented in Chapter 1 is a scientific introduction and discussion focusing on representative modeling works specified towards breast …

Assessing The Utility Of Phenylene Ethynylenes Against Candida Species Pathogens, Rina Sylejmani

Biomedical Engineering ETDs

Candida species are the cause of many bloodstream infections through contamination of indwelling medical devices. These infections account for a 40% mortality rate, posing a significant risk to immunocompromised patients. Traditional treatments against Candida infections include amphotericin B and various azole treatments. Unfortunately, these treatments are associated with high toxicity, and resistant strains have become more prevalent. As a new frontier, light-activated phenylene ethynylenes have shown promising biocidal activity against Gram-positive and -negative bacterial pathogens, as well as the environmental yeast, Saccharomyces cerevisiae. In this thesis, we monitored the viability of Candida species after treatment with a cationic conjugated …

Synthesis, Characterization, And Application Of Monosized Mesoporous Silica Nanoparticle-Supported Lipid Bilayers For Targeted Therapeutic Delivery To Individual Cells, Paul Durfee

Biomedical Engineering ETDs

Mesoporous silica nanoparticle (MSNP) supported-lipid bilayers, termed ‘protocells,’ represent a potentially transformative class of therapeutic and theranostic delivery vehicles. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single ‘magic bullet’. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous silica core can have variable size and shape to direct biodistribution and controlled pore size and surface chemistry to accommodate diverse cargos. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal …

Development Of Soft-Matter Delivery Systems: Coupling Ph Responsive Polymers To Porous Silica Particles, Andrew Gomez

Biomedical Engineering ETDs

This work investigates polymeric coating of evaporated induced self-assembly (EISA) mesoprous silica nanoparticles for potential use in controlled drug release and therapeutics. As demonstrated here, lipid bilayer coatings can be easily replaced with different polymer analogs allowing for dynamic response to environmental stimuli. In addition to coupling commercially available diblock polymers we synthesized and characterized a unique dual hydrophilic pH responsive diblock copolymer, PEO-PAA. This hybrid polymeric-nanoparticle system drastically improves targeting and release capabilities through the modular ability to couple multiple different polymers. Furthermore, this work is supported by an improved method to form and study giant polymer vesicles (pGVs)