Doctor of Philosophy, University of Akron, 0, Biomedical Engineering

Cancer is the second leading cause of death in the United States with breast cancer being the most commonly diagnosed type in women, accounting for 31% of cancers. Triple negative breast cancer (TNBC) is a particularly aggressive subtype, characterized by the lack of progesterone and estrogen receptors and low expression of HER2 receptors making TNBC extremely difficult to treat. Additionally, 46% of TNBC patients develop metastatic disease, where cancer cells invade through the primary tumor environment and form incurable metastatic tumors in other organs. Metastasis is heavily impacted by the tumor microenvironment (TME), which consists of an abundance of cellular and non-cellular factors that regulate tumor processes. The extracellular matrix (ECM) provides both structural support and signaling cues for cancer cells through common breast cancer proteins such as collagen, fibronectin (FN), and hyaluronan (HA). Our objective was to investigate how these proteins regulate invasion and the ability to self-renew of TNBC cells. We developed a three-dimensional tumor model to study effects of collagen, FN, and HA on invasiveness and stemness of TNBC cells. We developed an automated algorithm to analyze TNBC cell invasion, which we validated against traditional methods and through study of pharmacological inhibition of TNBC cell invasion. We then evaluated the effects of FN and HA on TNBC invasiveness and stemness and found that FN and HA alone significantly increase invasiveness but have no significant effect when combined. Molecular analysis showed that FN promotes RhoA/Rock signaling, whereas HA elevated CD44 receptor expression. These effects were significantly reduced when FN and HA were used together. We found significant microstructural changes in the ECM when both FN and HA were added to collagen, resulting in sheet-like structures which potentially reduced invasiveness of TNBC cells and activities of associated signaling pathways. We also found that FN and HA (open full item for complete abstract)

Master of Science in Biomedical Engineering, Cleveland State University, 0, Washkewicz College of Engineering

Reactive oxygen species (ROS), including peroxynitrite (ONOO⁻), play a crucial role in oxidative stress-related diseases, particularly cardiovascular complications, highlighting the need for precise detection mechanisms in biological systems. Selenium's established antioxidant properties, as evidenced in selenoproteins and its role in redox regulation, position it as an effective component for developing selective electrochemical interfaces for ROS detection. This study investigates selenium-based electrodeposition methods for creating sensitive and selective interfaces for quantifying peroxynitrite. Two approaches were explored: (1) electrodeposition of elemental selenium (Se) and (2) selenium-loaded graphene sheets (Se/GO). The morphology and chemical composition of these modified electrodes were analyzed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX), while their electrochemical performance was assessed using cyclic voltammetry (CV) and amperometry. X-ray photoelectron spectroscopy (XPS) further confirmed the uniform deposition of selenium and characterized its oxidation states. The electrochemical results demonstrated a notable shift in the oxidation peak of peroxynitrite by approximately 300 mV to a lower potential, confirming the electrocatalytic efficiency of elemental selenium. Selenium nanoparticles integrated into graphene sheets not only facilitated detection at lower potentials but also enhanced sensitivity by increasing the catalytic current. Under optimal conditions, the anodic peak current exhibited a linear relationship with peroxynitrite concentration from 1 to 10 µM, achieving a sensitivity of 300 nA/µM on Se/GO-modified CFE. The high oxidation state of selenium is significant in the catalytic reaction pathway, underscoring its efficacy in selective redox catalysis. Our findings highlight the potential of selenium-based modifications for the sensitive and selective electrochemical detection of peroxynit (open full item for complete abstract)

Master of Science in Biomedical Engineering (MSBME), Wright State University, 2024, Biomedical Engineering

This research explores how motor neurons (MNs) and Kv2.1 clustering change with age, emphasizing sex differences and MN subtypes. We found that MN density decreases with age in both sexes, while soma size increases in male mice. FF MNs were the most affected, and old weak mice had smaller MNs than their stronger counterparts, underscoring FF MN vulnerability. Baseline studies revealed that FF and FI MNs have larger Kv2.1 clusters compared to FR and S MNs. Female mice had smaller, denser Kv2.1 clusters than male mice, suggesting less clustering in females. With age, Kv2.1 clusters grew larger but became less dense and intense, indicating increased clustering. Old weak mice showed even more pronounced clustering than strong ones, linking Kv2.1 changes to age-related weakness. These findings highlight the susceptibility of FF MNs to aging and position Kv2.1 clustering as a key factor in motor neuron function and age-related decline.

Master of Science in Biomedical Engineering (MSBME), Wright State University, 2024, Biomedical Engineering

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron (MN) death resulting in paralysis and eventually death. ALS has greater prevalence in older populations sharing characteristics with aging like muscle weakness and MN type specific degeneration. MNs innervate skeletal muscles and control muscle contraction through their excitability which is altered in both conditions. C-Boutons are a cholinergic, excitatory synaptic input to MNs and have been studied in ALS and aging but have produced inconsistent findings and undesired gaps. We used immunohistochemistry to label mouse lumbar spinal cord and separate MN types. 60x imaging and automated analysis was performed providing robust 3D measurements. Our results presented similar findings between two ALS mutations with differing changes in a third mutation. We also show C-Bouton input with age undergoes sex and MN type specific reductions aligning with age-related weakness. Finally, we identify C-Bouton similarities and differences between ALS and aging.

Doctor of Philosophy, Case Western Reserve University, 2025, Biomedical Engineering

This dissertation explored the transformative potential of nanomedicine in cardiovascular diseases by deploying engineered nanoparticles to modulate immune responses, addressing underlying pathologies beyond symptom management. Focused on Antiphospholipid antibody syndrome (APS) mediated thrombosis and heart failure, this work innovates in two key areas: targeted thrombosis mitigation and cardiac fibrosis alleviation. For APS mediated thrombosis, star-shaped anti-PSGL-1-antibody-coated gold nanoparticles (aPSGL-1-AuNPs) were engineered and optimized to selectively target and neutralize PSGL-1 clusters on activated neutrophils. This approach significantly reduces thrombosis without increasing bleeding risks, revealing a strategic shift from broad anticoagulants to precision immunomodulation. For heart fibrosis, which is traditionally managed through symptom relief, this work discovered a Nano-Immuno-Metabolic Modulator (NIMM) that targets the spleen to upregulate Arginase 1 (Arg1) in macrophages. This innovative strategy suppresses splenic T cell expansion, thereby reducing cardiac fibrosis and enhancing cardiac function, marking a potential breakthrough in therapeutic methods. These applications of nanoparticles highlight their efficacy as precise tools in immune therapy and suggest a paradigm shift in cardiovascular disease management toward targeted treatments that minimize systemic side effects and improve patient outcomes. This work not only exemplifies the clinical promise of nanoparticles but also provides a foundation for their expanded use in treating complex cardiovascular conditions.

Master of Science (M.S.), University of Dayton, 2024, Bioengineering

Electrospun nanofiber (ESNF) membranes have attracted widespread interest in many applications due to their advantages in high specific surface area, high porosity, and structural controllability. This study combines gap electrospinning and electrolyte-assisted electrospinning techniques to develop a novel electrospinning approach for producing nanofiber mats of arbitrary geometry. A 3D printed conductive gelatin-based polymer electrolyte (GPE) solution is used as a geometric collector to focus the deposition of electrospun mats. The method utilizes syringe extrusion 3D printing of the GPE solution to produce a shape upon which ESNF are focused. The printable GPE ink is formulated to ensure it possesses the necessary conductivity, shear-thinning, and thixotropic properties. We have developed a gelatin-based GPE ink, enhanced with Laponite to improve shear-thinning properties and salts to increase conductivity. The 3D printing equipment then extrudes the GPE solution on the surface of the target device according to the pre-designed pattern. The optimized GPE solution formulation contained 8% w/v gelatin, 0.2% w/v Laponite, 2 mol/L sodium chloride, and 14.3% v/v glycerol, which was shown to meet the dual requirements of 3D printing and assisting electrospinning. The ink's conductivity was 8.02 S/m measured using a custom developed four-point probe system for gels. Rheological analysis demonstrated that the ink exhibits shear thinning (fluid behavior index n=0.223), which allows GPE ink to maintain a balance between easy extrusion and structural stability. We tested the electrospinning solution used during the experiment and investigated and characterized electrospinning operating parameters to explore several relationships between unrestricted mat diameter (UMD) and electrospinning operating parameters and GPE patterning threshold. The performance of the GPE ink was thoroughly examined experimentally: under the conditions of 25°C and 26% relative humidity, the (open full item for complete abstract)

PhD, University of Cincinnati, 2024, Engineering and Applied Science: Biomedical Engineering

Ultrasound imaging provides tongue shape information useful for remediating speech sound disorders, which affect 5% of children and cause long-term deficits in social health and employment in adulthood. However, ultrasound imaging can be difficult to interpret for clinicians and individuals, limiting the understanding of articulatory data and ultrasound biofeedback therapy speech outcomes. This dissertation includes three studies that use different approaches to address and investigate guidelines for improving interpretation of tongue articulation in ultrasound images during speech production. One difficulty is that tongue shapes can be challenging to compare due to their complexity and the fast pace of articulatory movements during speech. To approach this problem, tongue movement was represented as displacement trajectories of tongue parts, and support-vector machine classification models were trained to identify patterns that differentiate accurate versus misarticulated productions of the word “are.” A linear combination of tongue dorsum and blade movement was shown to achieve a classification accuracy of 85%. The resulting simpler representation of tongue movement accuracy would aid interpretation of ultrasound images during biofeedback by allowing easy comparison to movement targets. Another source of difficulty is the articulatory information missing from ultrasound images, such as tongue tip shadowed by sublingual air or by bone, as well as possible confusion between parasagittal and midsagittal tongue contours. By using a novel approach of simulating ultrasound wave propagation in tongue shapes segmented from MRI, ultrasound images were simulated from known /r/ tongue shapes. Simulations from 23 speakers indicated that tongue shapes in the middle of the continuum between bunched and retroflex /r/ had the longest portion of anterior tongue not visible in ultrasound images. Simulations of parasagittal and midsagittal images from 10 speakers su (open full item for complete abstract)

PhD, University of Cincinnati, 2024, Engineering and Applied Science: Biomedical Engineering

Hyperextension is commonly defined as greater than 0º extension and abnormal hyperextension is defined as greater than 5º past 0º extension[22,105,118]. In an in-vivo hyperextension study, a healthy intact knee was found to have up to 21.5º of hyperextension[53]. Hyperextension can also be a common injury resulting from neurological injury, physiological laxity, or other traumatic injuries and can cause posterior knee instability[26,31,61,100,139]. Several studies report limits of motion in the flexed knee and stop at 0º or perform sequential cutting studies that use the intact knee as a control measurement, thus there is little knowledge about joint movement in the intact hyperextended knee[42,53,95,106]. Structures that inhibit excessive hyperextension are disputed amongst experts and give rise to many potential structures such as the OPL, ACL, coronary ligament of the meniscus, or a combination of several soft tissues[26,31,100-101,106,115,139]. Furthermore, there are few biomechanical studies that have investigated specific causes for the restraint of hyperextension[101,106]. The purposes of this dissertation include understanding the six degrees of freedom of the intact hyperextended knee and variation amongst specimens and then identifying potential structures responsible for inhibiting excessive hyperextension in the knee. This research utilized a six degree-of-freedom robotic system to perform biomechanical testing on twenty-three, fresh-frozen cadaveric specimens. Two flexion-extension cycles, from 90º flexion to 25 Nm hyperextension, were applied to each knee while all other loads, except compression (25 N), were controlled to maintain 0 N/Nm. Sequential cutting studies to simulate injury were performed at 0º, the designated structure was sectioned, and testing began for the next cycle. All data used for analysis was extracted from the second testing cycle. Measurements made on the intact specimens revealed a positive relationship b (open full item for complete abstract)

PhD, University of Cincinnati, 2024, Engineering and Applied Science: Biomedical Engineering

This dissertation presents a multi-faceted investigation into the fluid-structure interactions (FSI), glottal flow dynamics, and acoustic outcomes across a variety of vocal fold models, including cadaveric human, excised canine, and synthetic vocal folds. By combining experimental methods such as planar particle image velocimetry (PIV), tomographic PIV (tomo-PIV), and computational simulations, this work aims to deepen our understanding of phonation mechanics, with implications for clinical voice research and synthetic model development. The first study explores subglottal stenosis and its significant impact on airway resistance, demonstrating through computational fluid dynamics (CFD) simulations that severe constriction leads to sharp increases in turbulent kinetic energy (TKE), supporting the use of virtual surgical planning to manage stenosis. The second study compares the aerodynamic and elastic properties of human, canine, and synthetic vocal folds, emphasizing the presence of vertical stiffness gradients (VSG) and flow separation vortices (FSV) in biological models. These findings underline the biomechanical complexity of tissue models and their implications for phonation, while identifying limitations in synthetic models, such as the absence of a VSG. The third study characterizes the VSG along the anterior-posterior axis in canine and human vocal folds, confirming the relevance of canine models in representing human tissue behaviors. The work enhances our knowledge of vocal fold elasticity, offering valuable data for both experimental and numerical models of phonation. The fourth study focuses on the FSI within the vocal folds, using ex-vivo canine larynges to capture intraglottal flow fields and characterize how VSG and glottal geometry influence phonatory efficiency and vortex formation. The results show that FSI is the primary factor for glottal flow skewing, advancing the understanding of three-dimensional (3D) flow dynamics during phonation. The fifth (open full item for complete abstract)

Master of Computer Science (M.C.S.), University of Dayton, 2024, Computer Science

The mouse cerebellar cortex, with its layered structure of molecular, Purkinje, and granular layers, refines motor control, coordination, and balance. Purkinje cells, the primary output neurons, process signals from parallel and climbing fibers and send inhibitory outputs to cerebellar nuclei, enabling motor learning and cognitive processing. Nowadays we have a better understanding of the cerebellar cortex's crucial roles in brain function and its implications in neurological disorders thanks to recent developments in neuroimaging, optogenetics, and electrophysiology that have clarified mechanisms underlying synaptic plasticity and signal processing within the region. Segmenting the cerebellar cortex is crucial for analyzing its cellular structure and connectivity, helping us understand motor control and learning processes. It enables detailed study of neural circuits and is key for investigating structural changes related to neurological disorders, aiding in targeted research and potential treatments. In this thesis, we apply various segmentation models to identify mouse brain cells through instance segmentation, focusing on precise classification of cell types and structures within the cerebellar cortex. We collect and annotate a dataset of 1000 images of mouse brain cells. We further evaluate different instance segmentation methods in two families, namely, transformer and non-transformer-based methods. Results indicate that non-transformer models outperformed transformer models in the small sized cells whereas transformer-based methods achieve better performance on large-sized cells. This thesis paves way to further research in using computer vision to understand mouse brain cells.

Master of Sciences, Case Western Reserve University, 2025, Biomedical Engineering

Exoskeletons, both commercial and experimental, are often misaligned due to the need for adjustability and mismatches in joint mechanics. However, the literature lacks understanding on how misalignments impact gait and how closely these devices need to be aligned. This study characterized these effects by systematically misaligning the exoskeleton and analyzing gait kinematics. Design priorities were refined to modify the device. The study also explored the utility of a pelvic belt to improve alignment. Results demonstrated the pelvic belt worsened gait as Gait Deviation Index (GDI) decreased by up to 27.61. Proximal and distal misalignments had a larger impact on gait and exoskeleton fitment with GDI reductions of up to 11.57 for distal misalignments compared to anterior/posterior misalignments, which showed GDI decreases of at most 7.01. A new design was proposed that prioritized proximal/distal alignment, addressing some misalignment effects.

Doctor of Philosophy, Case Western Reserve University, 0, EECS - Electrical Engineering

Timely characterization of the hemostatic system at the point-of-care/point-of-injury (POC/POI) is clinically important in traumatically injured and critically ill patients to guide therapeutic interventions and improve survival outcomes. This work advances the development of a microfluidic dielectric sensor, termed ClotChip, as a platform technology for POC/POI assessment of whole blood coagulation by enhancing its readout characteristics to precisely identify a range of blood coagulation disorders, including dysfunctions in fibrin formation and fibrinolysis. Specifically, two new distinct readout parameters in the ClotChip readout curve, namely, lysis time (LT) and maximum lysis rate (MLR) are identified and shown to be sensitive to the fibrinolytic status in whole blood. LT identifies the time that it takes from the onset of coagulation for the fibrin clot to mostly dissolve in the blood sample during fibrinolysis, whereas MLR captures the rate of fibrin clot lysis. A third new parameter, Smax, is also identified that represents the maximum permittivity slope and is shown to be sensitive to fibrin-polymerization defects during clot formation. These findings are validated through correlative measurements with rotational thromboelastometry (ROTEM) – a clinical, viscoelastic-based, global assay of blood coagulation. This work also includes the development of next-generation miniaturized dielectric coagulometry featuring multiple channels with bioreagent-functionalized electrodes that uniquely and specifically elicit differential responses from the multifactorial process of blood coagulation. Specifically, a microfluidic sensor is developed with physisorption of tissue factor and aprotinin on the electrode surfaces to probe the fibrinolytic function. The dual-coated microsensor can detect the hemostatic rescue in the hyperfibrinolytic profile of whole blood coagulation induced by tissue plasminogen activator as well as the hemostatic dysfunction due to concurrent pl (open full item for complete abstract)

Doctor of Philosophy, Case Western Reserve University, 2025, Biomedical Engineering

This dissertation focuses on non-perceptual effects of artificial sensation measured by effects in the motor system. Tactile feedback is used throughout the brain, from the “highest” cortical level to the “lower” spinal or brain stem level. Touch is first used before perception, or pre-perceptually, by the brain stem in simple, automatic modulation of the motor system. For example, carrying an object from place to place or even shifting it in one's hand involves many changing tactile signals. Even a single ridge of a fingertip supplies a unique signal for use in object manipulation. If one had to actively perceive and act upon all this information, merely picking up an object would become overwhelming. Fortunately, the lower levels of our brain automatically make minor adjustments to grip based on tactile information. What is not known is how relevant perceptual qualities are to these automatic corrections to grip. The cortex, not the brainstem, is the location of tactile perception, so it stands to reason that the brainstem does not require “natural” qualities of tactile feedback. Our lab has a group of participants with peripheral nerve cuff electrodes we can stimulation through. We tested how well artificial tactile feedback would integrate with the sensorimotor system in tasks of increasing complexity. We found that peripheral nerve stimulation is processed similarly to naturally generated touch with and without perception and may engage with the motor system as seen by the intent to modulate grip force.

Master of Science, The Ohio State University, 2024, Biomedical Engineering

Chronic wounds remain a persistent challenge to treat in healthcare due to recalcitrance. Our group has previously reported a printed electroceutical dressing (PED) made of screen-printed silver/silver chloride (Ag/AgCl) on a silk substrate that, when powered, produces hypochlorous acid in situ and has been proven in vitro and in vivo to reduce biofilms. With a shift of dressings to smart dressings that have wound monitoring capabilities, this project aims to add temperature wound monitoring to the PED as elevated wound temperature is correlated with biofilm infection. In this study, an 8.5 mm x 46 mm screen-printed Ag/AgCl resistance temperature detector (RTD) sensor was designed to be eventually implemented in a sensor array of five sensors within the PED. Sensor widths (0.50, 1.00, 1.25, and 1.50 mm) were tested, and a width of 0.5 mm was selected due to a noted increase in sensitivity (Ω/°C). A time-dependent resistance change was observed, and vacuum annealing was implemented to cure the sensors under a vacuum. Next, the width variation in printed sensors was quantified, and significant differences between sensors were determined. Due to width variations, resistance normalization was implemented to obtain a sensor calibration curve in a dry environment. Next, the sensor was calibrated in an agar tissue mimic, and a temperature coefficient of resistance (TCR) value of 0.319 %/°C was found. Validation temperature measurements were taken within a 30-50 °C temperature range, and the sensor was found to have an average percent error of 1.7 ± 0.9%.

Doctor of Philosophy, The Ohio State University, 2024, Materials Science and Engineering

This dissertation explores the application of thin-film materials in different fields of flexible electronics, with a final focus on their role in advanced human-machine interfaces (HMIs). Drawing on the unique properties of thin-film materials—such as stretchability, biocompatibility, and conformability—initial research efforts focused on developing individual sensing and actuation systems. Subsequent studies synthesized these technological advancements to engineer an integrated HMIs system, markedly enhancing interaction between humans and machines. These systems are particularly suited for wearable and implantable devices, where traditional rigid electronic systems fall short. The dissertation is structured around three main studies: the development of waterproof, flexible field-effect transistors for pH sensing in biofluids; a wireless, regeneratable biosensing platform for cocaine detection using pH-sensitive aptamers; and the application of sensor-actuator coupled interfaces to simulate gustatory experiences in virtual reality environments. Together, these studies demonstrate the potential of thin-film technologies in creating more adaptive, responsive, and efficient interfaces for health monitoring, biochemical detection, and immersive digital interactions.

PHD, Kent State University, 2024, College of Arts and Sciences / School of Biomedical Sciences

Wound healing is a very complex process requiring a well-orchestrated integration of multiple cellular and molecular events involving many players for antimicrobial activity and the promotion of new vascular formation. Acute wounds are healed by following the normal process of repair including inflammation, proliferation, and remodeling phases. If acute wounds fail to progress through the normal healing phases, it can develop into delayed healing or non-healing chronic wounds, particularly associated with the presence of bacterial biofilm (a community of bacteria encased in a protective matrix) and impaired angiogenesis. Conventional antibiotics frequently develop resistance and have limited efficacy against biofilm-associated wound infections. Approaches for promoting pro-angiogenic activity for wound healing have been relied on the use of bioactive molecules or growth factors, which have limitations in developing cost-effective treatment options. Additionally, thus far, each of the above aspects for antimicrobial and proangiogenic activities have been separately investigated to a great extent and an integrated approach to simultaneously addressing these three issues in a single drug delivery platform has yet to emerge. Wound scaffolds are biomaterial platforms designed to support tissue regeneration and enhance wound healing. In particular, nanoparticle-based scaffolds hold promise for treating chronic wounds due to their characteristics to exhibit higher reactivity due to high surface to volume ratio for improved cellular interactions, and easiness in surface functionalization, and controlled release of bioactive molecules. Additionally, their small size enables deep penetration into the wound bed. In this study, we propose to harness the unique characteristic of copper ion that can exhibit antibacterial and pro-angiogenic properties towards developing a cost-effective 33 scaffold for treating chronic wounds. Copper has emerged as an essenti (open full item for complete abstract)

Doctor of Philosophy, Case Western Reserve University, 2024, Biomedical Engineering

Cancer therapy has significantly advanced over the past few decades due to development of improved surgical technique, early detection, and novel therapy development. However, cancer remains one of the most lethal diseases due to metastasis, drug resistance, and recurrence. Immunotherapy holds the promise of utilizing the body's immune system to eliminate cancer cells. Immune checkpoint blockade therapy remains the most common utilization of immunotherapy in the clinical but yields varying degrees of success due to the massively immunosuppressed tumor microenvironment. Discovery of novel immune checkpoints and technology for targeting these checkpoints is critical for the advancement of cancer immunotherapy. The novel immune checkpoint protein VISTA (V-domain Immunoglobulin Suppressor of T cell Activation) impairs the toll-like receptor (TLR)-mediated activation of myeloid antigen presenting cells, promoting the expansion of myeloid derived suppressor cells, and suppressing tumor-reactive cytotoxic T cell function. Gene therapy targeting the VISTA checkpoint protein in conjunction with potent TLR agonists represents a safer yet potent alternative to antibody mediated cancer immunotherapy that has shown toxicity in the clinic. The overall objective of the work in this dissertation is to develop nanoparticle platforms for delivery of gene therapy mediate immune checkpoint blockade cancer immunotherapy regiments. First, a dual action lipid nanoparticle (Dual-LNP) that incorporates a VISTA-specific siRNA and a TLR9 agonist (unmethylated CPG) is developed. The Dual-LNP ensures co-delivery of both cargoes to tumor-infiltrating myeloid cells, leading to simultaneous silencing of VISTA and stimulation of TLR9. Next, the efficacy of the Dual-LNP was tested in multiple solid tumor models. The Dual-LNP treatment achieved a high cure rate in colon carcinoma MC38, melanoma B16F10, and YUMM1.7 models (83%, 60%, and 48%, respectively). Finally, investigation into the immune landsc (open full item for complete abstract)

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

SARS-CoV-2, the virus responsible for COVID-19 has been shown to induce syncytia formation, where multiple cells merge to form multinucleated giant cells. This phenomenon is driven primarily by the Spike protein of the virus, which also mediates viral fusion with the plasma membrane of target cells. This dissertation investigates the role SARS-CoV-2 Spike protein has on syncytia formation in epithelial and endothelial cells. My findings indicate that while syncytia formation is driven by variants of the Spike protein, there are significant differences in the frequency and size of syncytia. Notably, the Omicron variant produces smaller and less frequency syncytia compared to the Delta variant in epithelial cells. Additionally, exploring small molecule inhibitors may offer insights into the mechanism of syncytia formation. Understanding how syncytium formation disrupts the endothelial barrier could shed light on how SARS-CoV-2 infiltrates and causes multi-organ manifestations. These differences in syncytium formation are crucial for understanding the pathogenicity, transmissibility, and overall impact of SARS-CoV-2, providing valuable insights into COVID-19 severity and aid in the development of targeted therapeutic strategies.

Doctor of Philosophy, Case Western Reserve University, 2025, Biomedical Engineering

Due to recent advancements in the field of cancer imaging and diagnostic techniques, most solid human cancers are diagnosed at earlier stages while the cancer is still localized to a primary tumor site. For this reason, surgery remains the cornerstone of curative treatment with the primary objective of surgical intervention being the complete removal of the tumor, aiming to eliminate cancerous tissues. Ideally, this goal is achieved in a single surgical procedure, ensuring no residual malignant tissue remains. However, achieving complete resection can be challenging, particularly in traditional surgeries where surgeons primarily rely on gross visual inspection and tactile feedback to identify and remove the tumor. This increases the risk of leaving behind microscopic cancer cells that are not visible or palpable during the procedure. As a result, there is a significant risk of Positive Surgical Margins (PSMs), where cancer cells are present at the edge of the resected tissue. PSMs are a critical concern because they often result in tumor recurrence and necessitate additional treatments including adjuvant therapies, such as radiation therapy, chemotherapy and so on. These therapies, while essential for reducing the risk of recurrence, substantially increase the overall cost and complexity of treatment and add to the physical and emotional burden on patients, prolonging the recovery process and potentially impacting their quality of life. The challenge of achieving complete tumor resection underscores the need for improved surgical technologies and adjunct treatments that can enhance the live visualization of tumor removal and simultaneously treat the remaining tissues to reduce tumor recurrence and improve overall survival. To address these challenges, this research aims to enhance treatment strategies for prostate cancer (PCa) through innovative theranostic approaches utilizing Prostate-Specific Membrane Antigen (PSMA) as a key biomarker. PSMA is notably overex (open full item for complete abstract)

Doctor of Philosophy, Case Western Reserve University, 2025, Biomedical Engineering

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting adults with hallmark motor symptoms. Recent research has however shown it to be a multifaceted disorder with a myriad of non-motor symptoms. Eye movement deficits are an under-recognized and less understood symptom in PD, affecting at least half of the PD population in some form. Differentiating PD-related ocular motor deficits from age-related or congenital abnormalities presents significant challenges. Recent research has established a relationship between PD and ocular motor dysfunction, revealing that the pathological firing from the basal ganglia circuitry, where PD originates, disrupts the pathways controlling ocular motor behavior. This study delineates three primary ocular motor deficits in PD: vergence, saccades, and fixational stability or strabismus. Vergence is impaired by decreased gains, altered trajectories, and decreased fusion maintenance, leading to difficulties in maintaining binocular vision. Saccadic movements show decreased conjugacy, increased latencies, and slower trajectories, resulting in less accurate and coordinated eye movements. Fixational instability is observed as 12 increased exodeviation and an increased angle of strabismus, which further compromise visual stability. Additionally, our research explores the impact of therapeutic interventions on ocular motor behavior in PD. Deep brain stimulation (DBS), commonly used to manage motor symptoms such as tremor and rigidity in PD, also alters ocular motor function. Unlike levodopa, which produces no effect on OMD, DBS was shown to influence fibers in the ocular motor network. In 75% of cases with recognized PD-related ocular motor deficits, DBS improved vision-related quality of life to varying extents. However, the benefits of DBS on ocular motor responses depend on the specific location and region of stimulation, with some configurations potentially exacerbating the deficits. This (open full item for complete abstract)