Cellular and Molecular Physiology Commons^™

Effect Of Partial Ablation Of Skeletal Dynamin Related Protein 1 On Mitochondrial Health, Inflammation, And Fibrosis In A Mouse Model Of Duchenne Muscular Dystrophy, Tessa L. Duzz

Graduate Masters Theses

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder characterized by muscle weakness, degeneration, fibrosis, and impaired muscle regeneration. Mitochondrial dysfunction is an early pathological feature of DMD and has been linked to excessive mitochondrial fission. Dynamin-related protein 1 (Drp1) is a central regulator of mitochondrial fission, a key process in regulating mitochondrial quality and function. Inhibition of Drp1-mediated mitochondrial fission has shown promise as a potential therapeutic target for alleviating pathology and dysfunction in dystrophic muscle. The objective of this study was to determine whether partial skeletal muscle-specific ablation of Drp1 could improve muscle pathology and mitochondrial health in …

The Impact Of Tgfβ Conditioning And Socs3 Expression On Cytokine Signal Transduction And Inflammatory Gene Expression In Fibroblasts, Morgan Anderson-Crannage

NYMC Student Theses and Dissertations

Inflammation is a major driver in many aspects of recessive dystrophic epidermolysis bullosa (RDEB) pathology, including impaired wound healing, fibrosis, and potentially cutaneous squamous cell carcinoma development. Fibroblasts, as key stromal cells in the dermis, are responsible for orchestrating inflammatory responses through the secretion of cytokines and chemokines upon stimulation with IL-1α or IL-6. Suppressor of Cytokine Signaling 3 (SOCS3) functions as a negative feedback regulator of cytokine signaling and has emerged as a key modulator of inflammatory responses in immune cells and fibroblasts. Transforming Growth Factor Beta (TGFβ), a known driver of fibrosis in RDEB, has been implicated in …

Veratridine Suppresses Rictor-Mtorc2 Signaling Pathway In Colon Cancer Patient-Derived Xenograft Cells, Morgan Daniel Montgomery

Honors Thesis

Colorectal cancer (CRC) remains the second deadliest and fourth most common cancer in the world. The metastatic form of CRC is especially devastating due to a lack of effective and safer therapeutic options. Another challenge includes an increasing number of younger patients. Among critical signaling pathways overactivated in CRC, mTORC2 plays a key role in the progression of metastatic CRC, yet there is no selective mTORC2 inhibitor in the clinic. Interestingly, a natural plant alkaloid from the Veratrum genus, Veratridine (VTD), shows promise as VTD can upregulate UBXN2A, a colon-specific tumor suppressor protein. UBXN2A works with E3 ligases to ubiquitinate …

How To Search For The Engram: Optogenetics And Network Dynamics, Claudia Garcia Jou

Dissertations, Theses, and Capstone Projects

Memories are thought to be encoded by ensembles of neurons called "engram cells", because their artificial activation with optogenetics leads to the behavioral expression of a memory. However, the physiological mechanisms that mediate this process remain unknown. In this thesis, I investigate how optogenetic stimulation of memory-tagged cells changes neuronal firing, spatial coding, and the geometry of neural manifolds. I used an active place avoidance task and a foraging task to label engram cells in the dorsal hippocampus with Channelrhodopsin2 (ChR2). I then recorded the hippocampal activity response to optogenetic stimulation in mice under anesthesia, head-fixed, or freely moving. I …

Early Life Stress Mediates Cardiovascular Disease Risk Through Csf1r And Increases Risk Of Lupus Through Mature B-Cells, Cailin Elizabeth Kellum

ETDs from 2020-2029

The term Early Life Stress (ELS) encompasses traumatic events occurring before the age of 18 such as physical abuse, verbal abuse, household dysfunctions, sexual abuse, childhood neglect, child maltreatment, and adverse childhood experiences. The traumatic psychological and physical experiences in early life are widely known to cause enduring effects on mental and physical health in adulthood. Of note, individuals with ELS have adverse health outcomes earlier in adulthood and with more severity such as in the case of Systemic Lupus Erythematous (SLE), an autoimmune disease. The risk for autoimmunity and cardiovascular disease (CVD) increases with ELS exposure and CVD is …

Geographic Variation In Proteomic Responses To Ocean Acidification In A Cold-Water Coral (Balanophyllia Elegans), Keana A. Richmond

Cal Poly Humboldt theses and projects

In the face of a rapidly changing climate, assessing organismal responses to future stressors in the context of current, natural exposure to stress could provide key insights to understanding marine ecosystem resilience. I used Balanophyllia elegans, a cold-water, solitary, azooxanthellate coral as a model to better understand how varying oceanographic conditions across its geographic range have shaped its ability to tolerate and potentially adapt to current and future ocean acidification conditions. I collected B. elegans individuals from four sites across 2,500km of their range and subjected them to two pH treatments to investigate site-specific protein expression in response to …

Nutrient-Driven Transcription Factor-Dna Interactions And Their Signaling Mechanisms In Metabolic Disease, Evelyn A. Bates

Theses and Dissertations--Nutritional Sciences

Metabolic homeostasis is maintained through tightly coordinated signaling networks that integrate diverse physiological inputs. Central to this regulation are transcription factors, which sense nutrient, hormonal, and vitamin-derived signals and translate them into coordinated gene expression programs. Transcription factor activity is governed by DNA binding, recruitment of coregulatory proteins, and interactions with specific response elements in gene promoters, which allows them to selectively modulate diverse metabolic pathways. Owing to their multifactorial and tunable nature, transcription factors have emerged as promising targets for the treatment and diagnosis of metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). This dissertation explores the molecular …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

Expanding The Role Of Muscle Stem Cell Fusion In Muscle Under Hypertrophic Stimulus, Jensen Goh Zhong Sheng

Theses and Dissertations--Physiology

Muscle stem cells (MuSCs) are a unique stem cell population that can activate in response to both injury and growth stimuli. Studies on muscle regeneration have shown MuSC activation follows a uniform progression through proliferation, differentiation, and fusion. Therefore, to determine whether MuSC replication is a prerequisite for differentiation under hypertrophic stimulus, I used a lineage-tracking mouse model (Pax7^rtTA; TRE-H2B-GFP) to label MuSC nuclei and simultaneously tracked DNA synthesis via EdU incorporation. This dual-labeling approach allowed us to not only distinguish MuSC-derived nuclei but also demarcate which MuSC had proliferated prior to fusion. I then employed a mechanical …

A Tale Of Two Serpins: Pathologic And Protective Roles Of Agt And Pai-1 In Metabolic And Cardiovascular Disease, Alex C. Pettey

Theses and Dissertations--Physiology

Metabolic and cardiovascular diseases are leading causes of morbidity and mortality worldwide. Conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), aortic aneurysm, and cardiac fibrosis have limited pharmacological therapies, underscoring the need for deeper mechanistic investigations. Serine protease inhibitors (serpins) have been implicated in these pathologies and represent potential therapeutic targets. Despite structural homology, serpins regulate diverse physiological processes through both protease inhibition and non-inhibitory mechanisms. This dissertation examines the roles of two serpins, angiotensinogen (AGT) and plasminogen activator inhibitor-1 (PAI-1), in preclinical models of metabolic and cardiovascular disease to identify novel mechanisms that may inform future therapeutic strategies. …

Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici

Honors Undergraduate Theses

Manuka honey is known for its vital usage in wound healing, being an agonist towards fighting infections, and is an acting antioxidant [32]. Its main constituents are flavonoids and phenolic compounds, with methyl syringate (MSYR) being a major active ingredient. The specific compounds responsible for these antioxidant effects, particularly in the CNS, remain unclear. It is hypothesized that pre-treatment of mouse neuroblastoma cells with MSYR followed by hydrogen peroxide exposure will activate the AMPK/SIRT1/PGC-1a pathway, due to MSYR’s phenolic structure, and thus reduce oxidative stress and improve mitochondrial biogenesis. Hydrogen peroxide is a standard reactive oxygen species (ROS) treatment to …

Modulating Oran Nitrate-Reducing Bacteria To Enhance Nitric Oxide Bioavailability As A Therapeutic Target For Atherosclerosis, Donovan C. Davidson

CMC Senior Theses

Atherosclerosis remains the primary driver of global cardiovascular disease, yet clinical interventions are largely restricted to high-cost, invasive procedures only after it has reached a critical stage. Recent research has identified a connection between the oral microbiome and vascular health via the enterosalivary nitrate-nitrite-nitic oxide (NO) pathway. Oral nitrate-reducing bacteria (ONRB) drive the synthesization of NO by reducing dietary nitrate into nitrite, which is then converted into bioavailable NO. NO is a potent vasodilator that maintains endothelial health by suppressing inflammation through inhibiting the expression of adhesion molecules VCAM-1 and ICAM-1. However, this pathway is easily compromised by dysbiotic oral …

Gcn5l1-Mediated Lysine Acetylation Regulates Mitochondrial Dysfunction In The Aged Heart, Jackson Edmond Stewart

Graduate Theses, Dissertations, and Problem Reports (ETD)

For over a century, cardiovascular disease (CVD) has been and remains the leading cause of death globally. CVD risk and severity increase significantly with advanced age, and mitochondrial dysfunction has been implicated in the pathogenesis of aging. Furthermore, mitochondrial health is crucial for cardiac function, as one-third of total cardiomyocyte volume is occupied by mitochondria in order to meet the high energy demand of contractile and relaxational function. It is thus crucial that we understand the pathological mechanisms driving mitochondrial dysfunction in aging and how this contributes to age-associated cardiovascular disease. The current manuscript aims to fill this knowledge gap …

Exposure To Pm2.5 And Aging., Daniel Chris Gomes

Electronic Theses and Dissertations

Inhalation of fine airborne particulate matter (PM_2.5) is an environmental risk factor for numerous health disorders, including cardiovascular diseases (CVD). While several studies have shown that PM_2.5 exposure can induce oxidative stress, DNA damage, and inflammation, the underlying mechanisms that translate these effects into systemic pathology remain poorly understood. Some recent studies have shown that PM_2.5 exposure can lead to telomere shortening in leukocytes, but the generality of this outcome and contribution to endothelial dysfunction has not yet been fully explored. We hypothesized that PM_2.5inhalation accelerates cellular aging and senescence in both circulating peripheral …

Establishing Procedures For Primary Human Myoblast Cell Culture, Erica Duffy

Biomedical Engineering

Peripheral Artery Disease (PAD) affects an estimated 200 million people worldwide and is the leading cause of amputation in the United States. PAD is characterized by atherosclerotic narrowing of arteries, resulting in ischemia from reduced blood flow to distal tissues. Although surgical and percutaneous interventions can restore perfusion, fewer than 50% of patients experience sustained benefit, highlighting the need for alternative therapeutic strategies. One promising approach is promoting arteriogenesis, the growth and outward remodeling of pre-existing collateral vessels that improve blood flow around the occluded arteries. Arteriogenesis is regulated by regenerative, M2-polarized macrophages, making macrophage polarization a key therapeutic target. …

Advanced Interactions Of Directed Energy With Retinal Pigment Epithelial Cells And Their Photochemical And Photothermal Responses, Jin B. Ha

Theses & Dissertations

Excess optical radiation can injure the retina through either rapid heat deposition (photothermal damage) or cumulative photo‑oxidative stress (photochemical damage), yet current laser‑safety limits treat these mechanisms as independent. To test that assumption, this dissertation integrated systematic wavelength, duration and temperature‑controlled laser exposures with live/dead fluorescence imaging in a melanin‑loaded hTERT‑RPE1 monolayer model. First, concurrent 447 nm (blue) and 2 µm (infra‑red) beams delivered for 200 s demonstrated a strong thermal–photochemical synergy: each beam alone was sub‑threshold (≤25 % lethality) but together produced 100 % RPE death without exceeding 50 °C, proving that modest heating markedly lowers the photon dose …

Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells

Electronic Theses and Dissertations

Cardiac fibroblasts are central effectors of cardiac repair after myocardial infarction (MI). In response to signaling cues, they differentiate to a range of phenotypes with robust capacities to synthesize and secrete extracellular matrix (ECM) and signaling molecules. Although activated fibroblast phenotypes are associated with pronounced changes in metabolism, it remains unclear how the metabolic network upholds the effector functions of fibroblasts in the post-infarcted heart. Here, we identified that critical enzymes in the phosphoenolpyruvate (PEP) cycle, i.e. pyruvate kinase muscle-2 (PKM2) and phosphoenolpyruvate carboxykinase-2 (PCK2), are elevated in the heart after MI and examined their role in regulating post-MI remodeling …

Breaking The Rules: Post-Translational Modifications And Proteome Dynamics During Anoxia, Chelsea Jordan Hughes

Dissertations and Theses

Most organisms are ill-equipped to survive anoxia, but some organisms have developed molecular strategies to mitigate the cellular stressors associated with a lack of oxygen. While it is established that anoxic survival is contingent on metabolic suppression, it is unclear what mechanisms support this change in gene expression. Gene expression is regulated by a variety of mechanisms within the cell, including alteration of chromatin structure through histone modifications and protein modifications which contribute to the ever-changing proteomic landscape of the cell. Protein modifications such as ubiquitylation can lead to the degradation of proteins, while modifications to transcription factors can change …

The Role Of G6pd Variants And 3d Genomic Structure In The Development Of Pulmonary Hypertension, Christina M. Signoretti Ph.D.

NYMC Student Theses and Dissertations

Pulmonary hypertension is an under-recognized global health epidemic which is estimated to affect 1% of the population. It is associated with sustained mean pulmonary artery pressure greater than 20 mmHg, pulmonary artery remodeling, smooth muscle and endothelial cell proliferation and subsequent increased right ventricle hypertrophy due to increased afterload. Glucose-6-phosphate dehydrogenase (G6PD) is one of the key enzymes in the pentose phosphate pathway and has been previously linked to the development of pulmonary hypertension. G6PD deficiency is the most common human enzymopathy which affects approximately 400 million people worldwide and is a result of agricultural and epidemiological evolution in different …

Mechanisms Of Placental Impairment And The Upregulation Of Fetuin-B During Maternal Undernourishment, Mia Camilliere

NYMC Student Theses and Dissertations

Proper nutrition is crucial during pregnancy to support fetal and placental development. Failure to meet these nutritional needs can result in adverse health outcomes for both mother and baby. Despite its high prevalence in underdeveloped countries, maternal undernourishment is a public health issue worldwide. There are several possible causes of maternal undernourishment, and these can occur alone or in combination, such as poor access to nutrition, hyperemesis gravidarum, and drug use. This condition can adversely affect placental development and function to the extent of placental insufficiency, perturbing the entire pregnancy. The placenta is responsible not only for hormonally and physically …

Ammonia Regulation In Aedes Taeniorhynchus, A Salt-Water Mosquito, Joseph Edmonds

Undergraduate Honors Theses

The salt tolerant mosquito species Aedes taeniorhynchus has been observed in high salinity and ammonia conditions. Previous studies indicate Na+/K+ ATPase (NKA), the proton pump vacuolar-type H+ ATPase (VHA) and sodium-dependent cation-chloride cotransporters (NKCC’s) in sodium secretion in larval Aedes taeniorhynchus. However ammonia transporter such as Rh-protein, Amt1, and Amt2 have only been characterized in Aedes taeniorhynchus’s fresh water relative Aedes aegypti. Our research exhibits the expression of these transporters in A.taeniorhynchus using immunohistochemistry techniques. Evidence of VHA and NKA function in ammonia transport was characterized in vivo using drug antagonists in varying saline and ammonia concentrations. Ammonia flux rates …

The Antioxidant Potential Of Rosemary Leaf-Derived Nanovesicles, Shani Akila Griffin

Master's Theses

Human dermal fibroblasts are essential for maintaining skin homeostasis. However, exposure to exogenous and endogenous stressors can lead to fibroblast instability, extracellular matrix degradation, and excessive reactive oxygen species (ROS) production. These factors contribute to skin aging and ROS-induced skin disorders leading to hair loss. Adverse effects from synthetic treatments have driven interest in natural alternatives like plant extracts for skin therapy. However, the polyphenols in these treatments require an effective delivery system to ensure their stability and targeted application. Plant derived nanovesicles (PDNVs) are emerging as a promising natural alternative for therapeutic applications. Their biocompatibility, stability, and encapsulated compounds …

Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins

Biomedical Sciences ETDs

Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological …

Neuronal Tol-1 Integrates Microbial And Metabolic Cues To Modulate Feeding And Aversion In C. Elegans, Gursimran Singh Gujral

Theses, Dissertations and Culminating Projects

Toll-like receptors (TLRs) are key mediators of innate immunity, but emerging evidence suggests that they also play critical roles in the functioning of the central nervous system. This thesis explores the function of TOL-1, the Caenorhabditis elegans homolog of mammalian TLRs, in sensory neurobiology and behavioral responses to nutritive food. In particular, carbon dioxide and ethanol are commonly encountered in microbial environments and can signal metabolically active food sources or potential pathogens. Using tol-1 loss-of-function mutants, neuronal rescue lines, and a combination of molecular, tissue imaging, and behavioral assays, we demonstrate that TOL-1 functions in chemosensory neurons to regulate feeding …

Stromal Cells In The Small Intestine: Physiology, Localization, Function, And Alterations Induced By Chronic Arsenic Exposure, Scott Ventrello

All Dissertations

Arsenic is a prevalent toxicant found to affect around 94 to 240 million individuals in over fifty countries who are exposed to levels above the EPA and WHO standard of 10 ppb. As one of WHO’s top ten chemicals of public health concern, it is linked to several chronic diseases including diabetes, obesity, cancers, and inflammatory bowel diseases. Arsenic increases inflammation and disrupts the intestinal barrier in the small intestine and colon. Further, previous studies found that arsenic decreased secretory cell lineage and stromal cell gene expression markers in the small intestine. Thus, our goal was to investigate arsenic’s effect …

Investigating The Effects Of Hepatocyte Growth Factor On Primary Myoblast Proliferation, Grace Heller

Biomedical Engineering

Peripheral artery occlusive disease (PAOD) is a progressive vascular condition that affects over 200 million people worldwide and approximately 8 million in the United States. It is characterized by atherosclerotic narrowing of peripheral arteries, leading to reduced blood flow, ischemia, and, in severe cases, tissue loss and limb amputation. Although surgical revascularization is the gold standard, many patients—particularly those with comorbidities like diabetes— continue to experience poor outcomes, emphasizing the need for alternative therapies. One promising strategy is to enhance collateral arteriogenesis, the remodeling and enlargement of collateral arterioles that naturally bypass occluded vessels. Satellite cells (SCs), which give rise …

Metabolite Analysis To Understand Factors Limiting Microbial Fermentation At High Substrate Concentrations, Bishal D. Sharma

Dartmouth College Ph.D Dissertations

Clostridium thermocellum, a thermophilic anaerobic bacterium, holds promise as a biocatalyst for conversion of lignocellulosic biomass into biofuels. This microbe has been subjected to various metabolic engineering strategies, including the deletion of genes encoding secondary fermentation products such as H₂, formate, acetate, and lactate, as well as the expression of heterologous genes to redirect carbon flux toward ethanol production. Despite these efforts, achieving economically viable ethanol titers remains a challenge. We hypothesized that studying how intracellular metabolite concentrations change as fermentation stops could reveal metabolic bottlenecks or regulatory mechanisms limiting ethanol production at high titers. However, metabolomics studies at …

Metabolic Transitions In Embryos Of Artemia Franciscana: Regulation And Consequences For Oxidative Stress, Daniel Anthony Arabie

LSU Doctoral Dissertations

Embryos of Artemia franciscana survive harsh conditions in diapause and anoxia-induced quiescence for years by undergoing deep metabolic transitions. I investigated the relationship between phosphorylation of pyruvate dehydrogenase (PDH) and carbon flux to the tricarboxylic acid (TCA) cycle during metabolic depression. The difference in catalytic activity of the PDH complex (PDC) in maximally phosphorylated and dephosphorylated samples was 16.5-fold. Western blot analysis confirmed the changes in phosphorylation of PDH. Analysis of PDH expression in diapause and post-diapause embryos via phospho-PDH showed no significant differences. Investigation of post-diapause embryos under anoxia showed that phosphorylation of PDH decreased and activated the enzyme. …

Characterizing And Targeting The Non-Catalytic Functions Of Phosphatase Of Regenerating Liver 3 (Prl-3) In Oncogenesis And Cancer Progression, Jeffery T. Jolly

Theses and Dissertations--Molecular and Cellular Biochemistry

Phosphatase of Regenerating Liver 3 (PRL-3) is frequently upregulated in various cancers and is associated with poor patient prognosis. Although traditionally studied for its phosphatase activity, PRL-3 also interacts with the CNNM family of magnesium transporters through its catalytic site, and these two functions are mutually exclusive at any given time. Most previous studies relied on a commonly used PRL-3 mutation that disrupts both phosphatase activity and CNNM binding, making it challenging to determine which function drives its oncogenic effects. To address this gap in the field, I utilized a panel of PRL-3 mutants that selectively disrupt either phosphatase activity …

Assessing The Role Of Daily Thermal Fluctuations In The Performance Of Mitochondrial Energy Transduction Of The Centrarchid, Lepomis Cyanellus, Grayson Hofmann

Masters Theses

Freshwater systems are affected by current climate extremes, forcing species found in these systems to withstand drastic changes in temperature. Temperature changes affect these organisms by altering their metabolic rate and energy balance. Increases in temperature can lead to an increase in oxygen consumption, which ultimately increases the need for more energy production. Mitochondrial energy transduction of green sunfish (Lepomis cyanellus) and many other fish species after a thermal insult, has hardly been explored. This study complements the limited research available on mitochondrial function in similar species, as they ignore the possibility of consecutive thermal events, which are …