MSU Libraries Digital Repository (Michigan State University)
Not a member yet
106711 research outputs found
Sort by
ECOPHYSIOLOGY AND APPLICATIONS OF NITROGEN CYCLING COMMUNITIES
No full textThesis (Ph.D.)--Michigan State University. Microbiology and Molecular Genetics - Doctor of Philosophy, 2025Commercial greenhouse operations require sustainable strategies for water reuse and nutrient management to reduce agrochemical runoff. Nitrogen (N), a key plant nutrient, is prompt to leaching in the form of nitrate (NO3 12), contributing to environmental pollution and reduced fertilizer efficiency. Woodchip bioreactors (WBs) offer cost-effective solutions by using microbial communities to remove nitrate and degrade pesticides from greenhouse effluent.Chapter 2 investigates the dissimilatory nitrate reduction to ammonium (DNRA) in Trichlorobacter lovleyi SZ, a metal-reducing bacterium relevant to N cycling. Experiments under varying C:NO3 12 ratios showed that nitrite toxicity, not carbon limitation, restricts ammonification. T. lovleyi employs specialized respiratory and detoxification mechanisms to withstand nitrite stress, positioning it as a model organism for DNRA and identifying genes as markers for monitoring DNRA in engineered systems. Chapter 3 evaluates how hydraulic retention time (HRT) affects microbiome composition and agrochemical removal in 18-gallons bench-scale WBs. Experiments at 4, 24, and 48-hour HRTs showed that shorter HRTs favored rapid nutrient recycling but were less effective at pesticide degradation. Longer HRTs enhanced pesticide removal through increased contact time, sorption, and microbial taxa enrichment. Distinct microbial communities emerged at different HRTs, emphasizing HRT as a tunable parameter for optimized bioreactor performance. Chapter 4 investigates microbiome dynamics and functional stability in a year-long field study using a 1136 L woodchip bioreactor operated with a 25-minute HRT to treat greenhouse irrigation water. Despite daily fluctuations in nutrient and pesticide inputs, microbial communities acclimated within the first month and stabilized spatially across the bioreactor. Temporal shifts included the extinction of strictly anaerobic taxa such as Pirellula spp., likely due to gradual redox increases, while core taxa from Pseudomonadota and other phyla remained persistent. Metagenomic analyses revealed the consistent presence of genes encoding N, sulfur, and xenobiotic metabolism across metagenome-assembled genomes (MAGs), supporting the concept of functional redundancy, where key treatment functions were maintained despite taxonomic turnover. Overall, the system achieved over 99% N recycling and removed most detected pesticides, although further removal was needed for compounds with lower degradation potential (azoxystrobin). These findings highlight the resilience of the woodchip microbiome under real-world conditions and motivate the next phase of investigation, whether increased HRT can enhance pesticide removal without compromising nutrient recycling, as explored in Chapter 5. Chapter 5 builds upon Chapter 4 by evaluating microbiome seeding and extended HRT effects on bioreactor performance. Two bioreactors operated in parallel with identical influent water and a 1:2 mix of previously acclimated and fresh woodchips at 31- and 70-minute HRTs. Although seeding partially preserved some microbial taxa from prior acclimation, it did not significantly reduce the acclimation period or enhance community stability. Instead, HRT emerged as the dominant factor shaping microbial composition. Both short and extended HRT systems demonstrated comparable nutrient recycling (~98\u201399%) and pesticide removal efficiencies, suggesting shorter retention times (25\u201331 minutes) effectively balance performance with space efficiency. Chapter 6 presents a stakeholder survey assessing the feasibility and perceived value of WBs among Michigan greenhouse operators. While awareness of the technology remains low, participants recognized its potential benefits. Key barriers to adoption included limited technical knowledge, concerns about space, and economic uncertainty. These insights underscore the need for targeted outreach, financial incentives, and grower-engaged research to facilitate broader adoption. Together, this dissertation integrates mechanistic microbiology, field-scale bioreactor engineering, and stakeholder analysis to support the development of resilient, microbiome-informed systems for sustainable nutrient management and pesticide removal in greenhouse agriculture.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
DETERMINATION OF THE \u3b2-DECAY FEEDING INTENSITY DISTRIBUTIONS FOR NEUTRON-RICH NUCLEI NEAR THE Z = 28 AND Z = 50 SHELL CLOSURES USING TOTAL ABSORPTION SPECTROSCOPY
No full textThesis (Ph.D.)--Michigan State University. Chemistry - Doctor of Philosophy, 2025\u3b2-decay is the dominant decay mode for the vast majority of unstable nuclei that have been observed. As such, properties such as \u3b2-decay rates, \u3b2-feeding intensity distributions, and \u3b2- delayed neutron emission probabilities represent critical pieces of information across many areas of nuclear science, from studying the structures of nuclei to modeling astrophysical nucleosynthesis processes to nuclear safety and security applications. Although the properties of nuclei close to stability are largely well known, as one moves away from stability, cases where information is incomplete, incorrect, or unknown become common. This is especially the case for neutron-rich nuclei far from stability, many of which have been difficult or impossible to study thus far due to experimental constraints, creating a reliance on theoretical models to explain and predict the behavior of nuclei across the nuclear chart. Often the least well- characterized observable needed to calculate \u3b2-decay properties is the \u3b2-feeding intensity (I\u3b2) distribution, particularly for nuclei with high \u3b2-decay Q-values and fragmented decay schemes. Total Absorption Spectroscopy (TAS) is a well-known method for determining \u3b2-feeding intensity distributions utilizing high efficiency detectors to minimize the impact of the Pandemonium Effect.This thesis focuses on two experiments where the \u3b2-feeding intensity distributions for 73Co, 129In, 133Te, and 133mTe were determined using the Summing NaI (SuN) total absorption spectrometer. The first experiment involved observing the \u3b2-decay of 73Co, produced at the National Superconducting Cyclotron Laboratory (NSCL), while 129In and 133Te were produced using the Californium Rare Isotope Breeder Upgrade (CARIBU) ion source at Argonne National Lab. I\u3b2 distributions were determined by comparing the data collected from each experiment with simulated data via a chi-square minimization procedure. Results will be presented showing an unexpectedly high feeding to states in 73Ni from 73Co above the neutron separation energy, with significant competition between neutron and \u3b3-ray emission. The measured I\u3b2 distributions for 133Te and 133mTe show substantial deviations from the I\u3b2 distributions presented in the literature, with potential impacts on r-process nucleosynthesis calculations and models of radioactive decay heat in nuclear reactors. Finally, while the I\u3b2 distributions presented for 129In and 129mIn also show deviations from the literature consistent with expectations vis-\ue0-vis the Pandemonium Effect, however the presence of contaminant isotopes with similar \u3b2-decay characteristics introduce significant uncertainty in these results.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
ALZHEIMER\u2019S DISEASE MECHANISM AND DRUG DISCOVERY CENTERING ON HYPERPHOSPHORYLATED TAU
No full textThesis (Ph.D.)--Michigan State University. Biochemistry and Molecular Biology - Doctor of Philosophy, 2025Misfolding of hyperphosphorylated tau, a microtubule-associated protein, is a hallmark of Alzheimer\u2019s disease (AD) and other tauopathies. However, the mechanisms underlying tau-induced neurotoxicity remain unclear. In this study, I investigated the cellular effects of recombinant hyperphosphorylated tau (p-tau), produced via the PIMAX method. Upon uptake, p-tau triggered intracellular calcium elevation, endoplasmic reticulum (ER) stress, unfolded protein response (UPR), leading to apoptosis. Proteomic analysis revealed dysregulated proteins linked to neurodegeneration. These cellular responses could be mitigated by apomorphine, a brain-permeable drug currently used in Parkinson\u2019s treatment. Furthermore, I explored disease-relevant factors, including the frontotemporal dementia\u2013associated P301L tau mutation and various cholesterol metabolites, which modulated p-tau aggregation and toxicity. To identify potential therapeutic inhibitors, Kuo Lab and our collaborators utilized p-tau aggregation and cytotoxicity assays to perform a high-throughput screen (HTS) of 106,000 small molecules. Several compounds emerged as potent inhibitors against both p-tau aggregation and cytotoxicity with good drug-like properties. Medicinal chemistry optimization of the top hits improved biological safety, central nervous system (CNS) exposure, and efficacy, offering promising candidates for tau-targeted therapies. Together, this work uncovers cellular pathways driving p-tau pathology, identifies modulators of tau toxicity, and establishes a foundation for small-molecule drug discovery in AD and other tauopathies.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
UNDERSTANDING SOCIAL NETWORKS ON SOCIAL MEDIA : MACHINE LEARNING, SOCIAL INFLUENCE, AND SENSITIVITY ANALYSIS IN TWITTER DISCOURSES ON CRITICAL RACE THEORY
No full textThesis (Ph.D.)--Michigan State University. Measurement and Quantitative Methods - Doctor of Philosophy, 2025This dissertation brings together three interconnected studies that collectively examine online discourse surrounding Critical Race Theory (CRT) while advancing methodological innovations in evaluating machine learning (ML) model performance through sensitivity analysis. Study 1 employs a combination of natural language processing (NLP) and ML techniques to categorize CRT-related tweets, assessing both topical relevance and sentiment. It comparatively assesses various feature extraction methods and classification models for detecting tweets relating to CRT, school board recalls, and transgender student rights (TSR), as well as discerning right-leaning sentiments. Study 2 builds on the optimal models established in Study 1, using the influence model to investigate the influence process and the patterns of user engagement with these topics and sentiments. Focused on the Loudoun County school board recall, this study explores how exposure within Twitter networks influences subsequent tweeting behaviors, highlighting the amplification roles of both bot-like and human users in promoting right-leaning sentiments. Study 3 introduces a methodological innovation through the MCRINI sensitivity framework. Derived from the mathematical equivalence between the area under the ROC curve (AUC) and the Mann-Whitney-Wilcoxon rank-sum test, this framework conceptualizes ML model performance as robustness to rank shifts. It quantifies sensitivity in terms of the number of cases that need to be re-ranked in order to nullify the inference, which improves both interpretability and stakeholder engagement in social science applications of ML.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
Investigating Structure-Function Relationships in Cytochrome c Nitrite Reductase : Tuning Catalysis and Redox Cooperativity
No full textThesis (Ph.D.)--Michigan State University. Biochemistry and Molecular Biology - Doctor of Philosophy, 2025Soil microbes play a crucial role in reducing nitrogen loss from agricultural systems by converting nitrate to ammonium through the dissimilatory nitrate reduction to ammonium (DNRA) pathway. Central to this important pathway in the global nitrogen cycle is the pentaheme enzyme cytochrome c nitrite reductase (NrfA). NrfA is a soluble, periplasmic enzyme that catalyzes the six-electron, eight-proton reduction of nitrite to ammonium at a single active site. This reaction is facilitated by its redox partners, quinol oxidases. In Chapter 1, we review current knowledge on the regulation, homology,andmaturationofNrfA.InChapter2,wesummarizethelatestprogressinelucidatingthe reaction mechanism of ammonia production. Building on this mechanistic understanding, we next investigated the functional roles of two key hemes within the NrfA architecture. In Chapter 3, our goal was to determine the influence of heme 1\u2019s proximal ligand on active site tuning and catalytic efficiency. We replaced the coordinating lysine with a histidine to create an all-His variant that is found natively in some DNRA organisms. As expected, this variant demonstrated greatly reduced substrate affinity and catalytic efficiency but maintained roughly half of WT activity levels. The catalytic changes emphasizetheimportanceoffirst-andsecond-sphereresiduesonactivesitetuning and catalysis. In Chapter 4, we investigated the role of heme 5 which sits at the NrfA homo-dimer interface and is hypothesized to mediate electron sharing and/or electron storage. We introduced a site-directed H290M mutation, replacing the native heme 5 histidine ligand with methionine to create a functional knockout. Surprisingly, spectroscopic and electrochemical analyses revealed that this mutation significantly altered the redox potentials and reduction sequence of the hemes. These findings suggest that heme 5 may play a broader role in maintaining redox cooperativity across the hemes. Finally, in chapter 5, we characterized NrfA\u2019s redox partner and quinol oxidase, NrfH. Although still in early stages, our work on NrfH lays a foundation for future studies aimed at harnessing its electron-donating capabilities. Together, these findings advance our understanding of DNRAenzymologyandmayinformstrategiestoenhancenitrogenretentioninagricultural soils.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
A STATE OBSERVER BASED PROTECTION SYSTEM FOR MICROGRIDS : THEORY AND IMPLEMENTATION
No full textThesis (Ph.D.)--Michigan State University. Electrical and Computer Engineering - Doctor of Philosophy, 2025The protection of microgrids (MGs) is an emerging research topic due to the increasing integration of distributed generation (DG) based renewable energy resources (RES). Although a microgrid can operate in two modes: grid\u2014connected and islanded, protection against unexpected disturbances and faults in microgrid systems faces significant challenges due to the high penetration of RES, dual operation modes, and fluctuations in fault currents. Moreover, as microgrids proliferate and become increasingly smaller in size, the use of conventional protection methods can become unreliable and cost-prohibitive. This dissertation investigates the development of a protection system to alleviate the aforementioned issues.First, an integrated control and protection framework based on a state observer is developed and demonstrated. This framework enables the microgrid to detect faults and limit fault-current contributions. As the DGs are connected to the MG through power converters and the MG primarily supplies critical loads, the technical benefits of incorporating external fault-current limiters (FCLs) into the integrated protection framework are investigated to ensure power continuity and stable, reliable operation under all conditions. Second, the dissertation introduces a modern multi-function protection technique, where a decentralized Multi-Agent System (MAS) control strategy is utilized to enable reliable data exchange over the MG network. This framework can accommodate various functions, such as fault detection, isolation, and auto-reconfiguration. Third, this dissertation develops a dynamic state estimation based protection method using a linear state space model for each protection zone and real-time measurements, where a weighted least absolute value (WLAV) estimator implemented via linear programming estimates the system state. The protection logic is developed based on the residuals of the state estimation and the operational limits of the system to detect and isolate the faulted zone. Finally, a prototype digital relay-based control and protection integration scheme is developed, in which the relay is modeled using residuals from a state observer, phase-voltage continuity, and the circuit-breaker (CB) status of the protected component. The proposed digital relay is designed and tested in real time using the Real-Time Digital Simulator (RTDS), providing a high-fidelity environment for evaluating its performance under various fault scenarios. Its communication framework is based on the IEC 61850 standard.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
PRACTICING INTERPERSONAL CONFLICT FOR ANTIRACIST MEANS : REDRESSING SETTLER-COLONIAL LEGACIES OF INTERCULTURAL COEXISTENCE
No full textThesis (Ph.D.)--Michigan State University. Rhetoric and Writing - Doctor of Philosophy, 2025Using a nontraditional reporting structure, this dissertation approaches interpersonal conflict (IC) as a concept, practice, and theory for antiracist means. Interpersonal conflict is an expected, even mundane, experience of coexistence. Additionally, because IC is conceived and approached in different ways through racialized socialization, it can lead to harm and violence if approached uncritically. Thus, understanding conflict (broadly) and IC through an analysis of settler-colonialism, racism, and antiracism provides avenues for avoiding the default systemic violence we can inflict on each other as denizens of a settler-state and inheritors of its legacies and technologies. The introduction focuses on understanding race as a technology of settler-colonialism, and therefore, antiracism as a decolonial option. Through this understanding of race and settler-colonialism, conflict is theorized as a racialized practice that exists in a larger system of structural relations that cannot be uncritically ignored. The introduction is meant to offer a larger framework in which IC exists as one example of the way systemic violence is made possible in our bodies. Chapter I focuses on moments of IC in a research study on antiracist practice that led to further theorizations of conflict and the need to understand the role of IC in academic professional settings. The next two chapters arise as avenues of change derived from these considerations. Chapter II focuses on revisiting the methodology of that original study to offer more robust antiracist methodological practices for further studies based on the moments of IC experienced. In particular, expanding the consent process and foregrounding the role of emotional labor in data collection for participants are offered as antiracist methods that address the possibility and reality of IC more critically. Chapter III focuses on presenting an antiracist professional development (PD) curriculum focused on more self-aware and critical approaches to IC in intercultural academic professional spaces. As a model for the self-work necessary for antiracism, this theorization and presentation of an antiracism PD curriculum is meant to address what to do with the inevitability of conflict in intercultural academic spaces and how to make something with it as opposed to uncritically living with it. Through analyzing IC in the specific context of academic professional spaces, this dissertation hopes to model how to apply larger systems analysis of settler-colonialism into mundane everyday existence. The hope here is that in these micro interventions we might learn to make do with our enculturation in settler-colonialism in ways that reduce harm and, maybe, offer decolonial options for coexistence.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
A TALE OF TWO THYLAKOID-ASSOCIATED LIPID DROPLETS : UNDERSTANDING CYANOGLOBULES AND PLASTOGLOBULES
No full textThesis (Ph.D.)--Michigan State University. Biochemistry and Molecular Biology - Doctor of Philosophy, 2025Thylakoid-associated lipid droplets, long thought to be inert lipid storage bodies, haverecently emerged as dynamic and multifunctional organelles. Plastoglobules (PGs), in particular, have emerged as key thylakoid-associated lipid droplets, known for their involvement in lipid metabolism, redox buffering, and more recently, in stress signaling and hormone biosynthesis. Yet, fundamental questions remain regarding the evolutionary origins of PGs, their mechanisms of formation, and their broader physiological significance. This dissertation addresses these gaps through a cross-kingdom investigation of thylakoid-associated lipid droplets, revealing mechanistic and evolutionary insights that reshape our understanding of LD biology from cyanobacteria to plants. Chapter1 provides a conceptual foundation for this work by examining the current understanding of PGs, emerging data on cyanobacterial LDs, and their evolutionary context. Chapter 2 of this dissertation presents the first identification and in-depth characterization of cyanobacterial lipid droplets in Synechocystis sp. PCC 6803, here defined as cyanoglobules (CGs). CGs exhibit features similar to PGs, including dynamic morphology, monolayer boundaries, and enrichment in prenyl lipids and redox-active compounds such as plastoquinone derivatives. Through lipidomics and proteomics, I show that CGs contain orthologs of plastoglobule proteins found in Arabidopsis thaliana, supporting an evolutionary link between prokaryotic and eukaryotic plastidial LDs. Deletion mutants for CG-associated proteins displayed phenotypes affecting pigmentation, photosynthesis, and growth, indicating their role in stress resilience and organismal adaptation. Chapter 3 expands the analysis to Anabaena sp. PCC 7120 in a non-nitrogen-fixing background strain. Under nitrogen deprivation, CGs accumulate significantly, exhibiting conserved yet species-specific lipid and protein profiles. This chapter further establishes CGs as stress-responsive compartments involved in lipid remodeling and redox buffering, mirroring PG behavior during plant senescence and high-light stress as well as the same LDs which is CGs in Synechocystis. In Chapter 4, I expand the research on understating the biogenesis of CGs by investigate the biogenesis of CGs using mutants in the Esterase/Lipase/Thioesterase (ELT) gene family in Synechocystis which the single mutant of this family previously known to have lesser CGs. In this chapter, I found that a double mutant (slr2103/slr1807) exhibits a "stay-green" phenotype ii under phosphorus deficiency, resembling Arabidopsis pes1/pes2 plastoglobule mutants under dark induced senescence. This phenotype suggests functional conservation in pigment recycling and stress response, offering a mechanistic model for plastidial LD evolution. The study positions CGs as mobile, adaptive compartments integrating lipid metabolism with environmental signaling in cyanobacteria. In Chapter 5, I explore the plastoglobule-localized Esterase/Lipase/Thioesterase 4 (ELT4) protein in Arabidopsis thaliana, revealing a previously unrecognized role for plastoglobules in hormone biosynthesis and developmental regulation. ELT4, initially uncharacterized, was identified as one of three ELT proteins exclusively localized to PGs, alongside PES1 and PES2. Through analysis of mutant and overexpression lines, phenotypic characterization, and hormone profiling, I show that ELT4 is functionally connected to the jasmonic acid (JA) pathway 12a key regulator of plant stress responses and male fertility. The elt4 single mutant exhibits partial male infertility and delayed flowering, alongside hallmark JA- defective phenotypes such as anther indehiscence and shortened stamen filaments, which are rescued by exogenous JA application. Notably, the triple mutant pes1pes2elt4, results in complete sterility, underscoring potential functional redundancy or additive effects within this enzyme family. While the precise enzymatic role of ELT4 in JA metabolism remains to be elucidated, these findings suggest a broader, previously underexplored role for plastoglobule- localized enzymes in linking plastidial lipid metabolism to hormone-regulated reproductive development. Chapter 6 provides an integrated synthesis of these findings, presenting a unifying model where plastidial lipid droplets 12both CGs in cyanobacteria and PGs in plants 12are framed as evolutionarily conserved, metabolically active, and functionally versatile organelles. Future directions include elucidating the molecular mechanisms of CG biogenesis, cross-species functional validation of ELT4, and dissecting the molecular pathways through which ELT4 modulates hormone signaling and contributes to stress responses and developmental regulation.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
Structure Preserving, Deep Learning Methods for Fluid Moment Models
No full textThesis (Ph.D.)--Michigan State University. Applied Mathematics - Doctor of Philosophy, 2025This dissertation collects results in applying neural networks to problems associated with fluid moment models in kinetic gas dynamics. Governed by the Boltzmann transport equation, gas dynamic problems are high dimensional problems and fluid moment methods are an approach to reduce the dimensionality to facilitate computation. But this reduction in dimension risks losing features and properties that are present in the higher dimension setting.We present our work developing neural network methods to solve the moment closure problem to the Boltzmann equation with the BGK approximation. Our network is trained on higher dimensional data to create closures that capture kinetic features while maintaining lower dimensional moment models. Then we turn our attention to applying neural networks to approximate Maxwellian boundary conditions for the moment problem, again with the hope of preserving kinetic features of the boundary in moment models. Finally, we explore properties of recently developed neural network architectures that allow Lipschitz and bi-Lipschitz control between layers. This is done to exposition the features of these new architectures and investigate if applying this architecture to our neural network closures improves performance and accuracy in difficult regions.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references
MOLECULAR MECHANISMS OF OBESITY-DRIVEN CARCINOGENESIS : IMPLICATIONS FOR SKIN CANCER AND MULTIPLE MYELOMA
No full textThesis (Ph.D.)--Michigan State University. Pharmacology and Toxicology-Environmental Toxicology - Doctor of Philosophy, 2025The National Cancer Institute defines cancer as a disease characterized by the uncontrolled proliferation of cells that can invade and spread to other parts of the body. In 2022, around 20 million new cancer cases were recorded worldwide, and estimates indicate this figure may increase to 29.9 million in 2040. The etiology of cancer is multifactorial and afflicts many tissue types, causing millions of deaths worldwide. Therefore, it is imperative to develop novel drugs for both prevention and treatment. Obesity is a risk factor for several types of cancer, including breast, prostate, and colon cancer and contributes to disease progression. However, the influence of obesity on the development of nonmelanoma skin cancer (NMSC), the most common type of cancer, remains unclear. The first objective of this dissertation is to understand how obesity may contribute to the development of NMSC, specifically the transformation of benign actinic keratosis into potentially invasive cutaneous squamous cell carcinoma. RNA-Seq analysis of a cell line identified Angiopoietin-like 4 (ANGPTL4) as a potential target of adipocyte-secreted factors in keratinocytes that support growth. Immunohistochemistry staining of lesional skin biopsies revealed that ANGPTL4 is linked to the early stages of NMSC development, with high levels expressed in actinic keratosis and cutaneous squamous carcinoma in situ. The protein was absent in the keratinocytes within the invasive squamous cell carcinoma, suggesting the early role of this protein in NMSC development. These data suggest that targeting ANGPTL4 may offer a novel therapy for preventing the progress of NMSC. Additionally, patients with high ANGPTL4 levels or those with obesity may represent a critical demographic for risk assessment and therapeutic intervention. The second objective of this dissertation is to identify novel compounds that could be developed into drugs for multiple myeloma. Multiple myeloma is a cancer associated with obesity that is currently incurable because patients become refractory to treatments. Through a phenotypic and target-based screening approach, some compounds were identified that can be optimized for the treatment of multiple myeloma. The first compound, MSU-43222, proved effective against dexamethasone-resistant multiple myeloma cell lines, with low toxicity observed in peripheral blood mononuclear cells (PBMC). The second group of compounds, which were GPR68 inhibitors (OGM1, R, and R17 significantly decreased the viability of human multiple myeloma cell lines (MM.1S cells). They also induced the expression of ferroptosis-related genes (ATF4, CHAC1, and SLC7A11) and increased lipid peroxide levels in MM.1S cells. These GPR68 inhibitors provide an alternative approach to targeting apoptosis-resistant multiple myeloma patients. Overall, this thesis reveals promising approaches for therapeutic interventions in preventing and treating obesity-related cancers, including NMSC and multiple myeloma.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references