Cell and Developmental Biology Commons^™

Analysis Of Developmental Cardiogenic Processes Mediated By Fox And Zinc-Finger Transcription Factors, Rajnandani Katariya

All-Inclusive List of Electronic Theses and Dissertations

Cardiogenesis is a highly choreographed biological process requiring the precise integration of gene regulatory networks to govern cell division, fate determination, and spatial positioning. Disruptions in these mechanisms lead to congenital heart defects (CHDs), which affect approximately 1% of live births globally. Due to the evolutionary conservation of cardiac signaling pathways and the structural homologies between the Drosophila dorsal vessel and the early vertebrate heart tube, Drosophila melanogaster serves as a powerful model for dissecting the fundamental mechanisms of heart development. This dissertation investigates the molecular orchestration of cardiac development, specifically focusing on the roles of the transcription factors Jumu …

Unveiling The Biochemical Pathway Responsible For Ankyloglossia (Tongue-Tie) By Tracking Enzymatic Activity Of Apoptosis Pathways, Becca Ringstad

Celebrating Scholarship and Creativity Day (2018-)

Ankyloglossia (Tongue-tie) is a condition that is caused by failed cellular degeneration leading to a short lingual frenulum. This short lingual frenulum tethers the tongue to the bottom palate of the mouth and leads to problems, including breastfeeding for infants, depriving them of important proteins that build the gut microbiome, strengthen the immune system, and fight off antigens. If left untreated, it leads to problems with speech articulation, airway development, and obstructive sleep apnea. Treatment involves a frenectomy, which is the release of the short lingual frenulum using surgical scissors or a laser. Ankyloglossia can occur with conditions such as …

The Impact Of Glucose Exposure On Organic Cation Transporters (Oct) Function In A Corneal Epithelial Cell Line, David A. Garza

Theses & Dissertations

Organic cation transporters (OCT) facilitate the movement of neurochemicals and medications, contribute to the removal of cellular waste, and facilitate neuronal communication. Three subtypes of these high-capacity, low-affinity transporters (OCT1, OCT2, and OCT3) are differently expressed in peripheral tissues such as the liver, kidneys, as well as the central nervous system. OCTs are also expressed in ocular tissues. Chronic hyperglycemia is a complication commonly associated with diabetes that can lead to ocular diseases such as diabetic keratopathy, which affects the cornea. In this project, we expose immortalized human corneal epithelial cells (HCE-S) to various glucose concentrations to study their impact …

Inosine Accelerates Cancer Cell Killing By The Experimental Antifolate Ucp1162: Implications For Novel Combination Treatments, Reshma Ramesh, Charles Giardina, Alan Kuo

Honors Scholar Theses

Antifolates disrupt one-carbon metabolism (OCM), which stops nucleotide synthesis and therefore slows down cell proliferation. Our experimental antifolate, UCP1162, stops de novo purine synthesis and thymidine synthesis by targeting the OCM pathway. We investigated whether the downstream metabolites of OCM pathway: methionine, thymidine, and inosine, affect the cell death caused by UCP1162 using MV4-11 leukemia cells. Thymidine was found to partially rescue MV4-11 cells from UCP1162, in contrast, inosine was found to accelerate the cell death caused by UCP1162. These cytotoxic effects of UCP1162 alone and in combination with inosine were irreversible, as removal of treatment did not restore cell …

The Development Of A Crispr-Based Calibrated Functional Assay For Classifying Pathogenicity Of Msh2 And Msh6 Variants In Lynch Syndrome, Olivia N. Amodeo

Honors Scholar Theses

Lynch syndrome is a hereditary disease caused by the inheritance of a mismatch repair gene variant. Individuals with this condition are predisposed to cancer development, most commonly colorectal cancer. Current guidelines for variant classification are based on numerous evidence categories, including functional evidence. However, many novel clinical variants are not well characterized, and evidence is difficult to obtain if functional assays are not calibrated.

To address this, our lab created a calibrated functional assay that calculates an odds of pathogenicity score for MSH2 and MSH6 gene variants that can be used as evidence for classifying variants of uncertain significance. This …

Reversible, Light-Controlled Inhibition Of Stim1-Mediated Calcium Signaling Using Photoswitchable Ml-9 Derivatives In Jurkat-Lucia Nfat Reporter T Cells, José L. Matute Gálvez

Honors Scholar Theses

Store-operated calcium entry (SOCE) through calcium release-activated

calcium (CRAC) channels is the dominant pathway for sustained Ca2+ influx in

non-excitable cells and is essential for T cell activation, driving downstream

signaling through the calcineurin-NFAT transcriptional axis. Dysregulation of

SOCE produces multi-systemic disease phenotypes, establishing that precise,

spatiotemporally controlled modulation of this pathway is a fundamental

therapeutic requirement. ML-9 is one of the only characterized small molecules

capable of targeting SOCE upstream at the level of STIM1 localization, but lacks

the selectivity, pharmacokinetic properties, and spatiotemporal control necessary

for therapeutic development.

This work describes the design, synthesis, and biological evaluation of …

Diacylglycerol Kinase Eta As A Novel Target In Nras Mutant Melanoma, Haley P. Wilson, Casey D. Stefanski, Signe Caksa, Glenn L. Mersky, Scott D. Varney, Jelan I. Haj, Dan A. Erkes, Timothy J. Purwin, Vivian Chua, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

NRAS mutations occur in 10%-30% of cutaneous melanomas and are associated with high tumor mutational burden. Mutant NRAS signaling drives aberrant cell growth and proliferation, in part, through activation of the RAF-MEK-ERK1/2 kinase pathway; however, targeted therapies to this pathway have limited effectiveness in patients with NRAS mutant melanoma. The role of other targetable signaling pathways in NRAS mutant melanoma is poorly characterized. Here, we demonstrated that one isoform of diacylglycerol kinase, diacylglycerol kinase eta (DGKη), a lipid signaling regulator, was highly expressed in NRAS mutant melanoma patient samples. Knockdown of DGKH in NRAS mutant melanoma cell lines resulted in …

Effects Of M6a Dna Methylation By Bacterial Methyltransferase In Colorectal Cancer, Fabian Alejandro Mendoza Galvan

Dissertations and Theses (Open Access)

Effects of m6A DNA methylation by bacterial methyltransferase in colorectal cancer Fabian Alejandro Mendoza Galvan Advisory Professor: Angela H. Ting, Ph.D. Fusobacterium nucleatum animalis (Fna) is found in the human oral cavity and gut. A distinct clade of Fna is primarily enriched in the tumor microenvironment (TME) and within colorectal cancer (CRC) cells. This clade DNA methylation pattern is primarily catalyzed by a cell-cycle regulated methyltransferase (CcrM) ortholog, M.FnI, that targets the GANTC sequence motif through methyl-6-Adenine (m6A) DNA methylation. We hypothesized that M.FnI enzyme can induce m6A methylation abnormalities in CRC cells to promote cancer progression. Evidence for endogenous …

Targeting Breast Cancer Brain Metastasis Through Novel Combination Of Fda-Approved Orally Active Blood-Brain Barrier Permeable Ret And Tgli1 Inhibitors, Joshua Cha

Dissertations and Theses (Open Access)

Breast cancer is the most diagnosed cancer in American women, and breast cancer brain metastasis (BCBM) exhibits the worst prognoses with a life-expectancy averaging at 6 months. This short life expectancy is largely attributed to the lack of effective treatment. Many challenges remain unsolved, including the limited number of actionable targets for targeted therapy and effective blood-brain barrier (BBB) permeable drugs that are safe without promoting drug resistance. Therefore, there is an urgent call for identification of novel therapeutic targets and development of BBB-permeable drugs. One of the potential targets identified by our lab for BCBM targeted therapy is the …

From Antigen Presentation To Tumor Control: Mechanisms Of Type I Conventional Dendritic Cell-Based Cancer Vaccines, Josue E. Pineda

Dissertations and Theses (Open Access)

Type 1 conventional dendritic cells (cDC1s) are important for generating and sustaining antitumor immunity. Accordingly, the abundance of cDC1s in human tumors correlates with improved outcomes in cancer. Capitalizing on this role, we previously demonstrated that vaccination with in vitro-derived murine cDC1s elicits durable tumor control in multiple preclinical models; however, the immunological mechanisms underlying the efficacy of cDC1 vaccination remain unclear. Here, we examined whether in vitro-derived cDC1s resemble tumor-infiltrating DC populations and whether MHC-I and MHC-II antigen presentation contribute to cDC1-mediated tumor control following vaccination in melanoma.

As expected, MHC-I- or MHC-II-deficiency had minimal impact on …

Understanding Epigenomic Landscapes In Cancer Progression And Immunotherapy Response, Jonathan Schulz

Dissertations and Theses (Open Access)

Nonmutational epigenomic reprogramming has emerged as a key hallmark of cancer that plays crucial roles in tumor evolution during its progression and response to therapy. However, the extent and nature of epigenomic reprogramming remains poorly understood. This dissertation examines how epigenetic regulation shapes cancer progression and response to immunotherapy. Working at the intersection of cancer biology and computational genomics, it develops analytical frameworks for characterizing chromatin structure and DNA methylation across diverse tumor contexts and uses these frameworks to address two complementary biological questions: how promoter-associated chromatin organization varies across cancer types, and how epigenetic perturbation modulates tumor immunogenicity in …

Abnormal Trafficking And Processing Of Multiple Matrix Metalloproteinases Drive Cartilage Defects In Congenital Disorders Of Glycosylation, Chia-Lun Wu

All Dissertations

Congenital Disorders of Glycosylation (CDG) are rare metabolic diseases caused by defects in glycosylation. Despite identification of over 200 CDG types, the mechanisms linking glycosylation defects to diverse clinical phenotypes remain unclear. This dissertation uses zebrafish models of PMM2-CDG and STT3-CDG to redefine CDG pathogenesis, shifting from a simple glycan deficiency model to one involving disrupted cellular spatial organization.

We identify a protease-dependent pathway underlying craniofacial cartilage defects. Specifically, defective proteolytic processing of N-cadherin, a key adhesion molecule in chondrogenesis, is a central driver of pathology. We further uncover an unconventional trafficking mechanism in which ER stress and altered secretory …

Assessing The Use Of Exon-Skipping Morpholino Antisense Oligonucleotides Targeting The Different Sumo Paralogs As Enhancers Of The Antitumor Activity Of Chemotherapeutic Agents, Andrea Teresa Garcia-Morin

Open Access Theses & Dissertations

Post-translational modifications (PTMs) are critical regulators of protein function, stability, and localization, with SUMOylation emerging as a key modulator of cellular stress response and survival in cancer. Non-small cell lung cancer (NSCLC) is characterized by heightened dependence on SUMOylation to sustain pro-survival signaling, DNA repair, and resistance to chemotherapy. This dissertation investigates a novel chemosensitization strategy based on the splice-switching of SUMO transcripts in NSCLC cells using exon-skipping morpholinos (ESMs), which redirect splicing toward non-conjugatable SUMO alpha isoforms, thereby reducing global SUMOylation. We hypothesized that decreasing global SUMOylation through forced alternative splicing of SUMO transcripts would impair the stress-protective functions …

Novel Roles Of G-Beta-Gamma Signaling In Microtubule Dynamics And Neurodegeneration, Diana I. Olivas

Open Access Theses & Dissertations

Neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), are characterized by progressive neuronal dysfunction, cytoskeletal disruption, and cognitive decline. Although Tau hyperphosphorylation and neurofibrillary tangle (NFT) formation are classical hallmarks of AD, emerging evidence suggests that microtubule (MT) dysfunction may precede and occur independently of Tau pathology. Understanding upstream regulators of MT dynamics is therefore critical for elucidating early mechanisms of neurodegeneration. Previous work from our laboratory demonstrated that G protein βγ (Gβγ) subunits directly interact with tubulin and promote MT assembly. However, the mechanism of Gβγ signaling in neuronal cytoskeletal stability and neurodegeneration remained poorly understood. The present study investigated …

Characterizing The Molecular Response Of Embryonic Zebra Finch To Acute Sound Playback, Saidat O. Adeniran-Obey Miss

All Theses

Auditory stimuli are important cues that influence developmental plasticity in animals and are important for development and adaptation to an ever-changing environment. In the zebra finch (Taeniopygia guttata), there is evidence of adaptive developmental reprogramming in response to a prenatal ‘heat call’. Embryos exposed to this heat call exhibit changes in growth rate post-hatch, increased heat resistance, and enhanced reproductive success at maturity. However, it has long been assumed that embryonic zebra finches cannot respond to sound due to the immaturity of their auditory system. These findings raise the critical question of whether late-stage zebra finch embryos can, …

Mechanistic Insights Into Enterolactone-Mediated Glut4-Dependent Glucose Uptake, Merritt Smith

Senior Honors Theses

Type 2 diabetes mellitus (T2D) is one of the leading causes of morbidity and mortality in the United States, with approximately 25% of healthcare expenditures directed toward its management and associated metabolic complications. In response to the urgent need for novel therapeutic strategies, recent research has focused on bioactive compounds derived from dietary sources. In light of that, we identified the plant lignan matairesinol (MA) and its gut-derived metabolite, enterolactone (ENL), as agents capable of enhancing glucose uptake in 3T3-L1 differentiated adipocytes. These results suggest that enterolactone may represent a promising dietary supplement for improving glycemic control in patients with …

Discovering The Genetics Underlying Speciation Traits In Heuchera (Coral Bells), Tajinder Singh

Honors Theses

Hybridization is a key evolutionary mechanism for generating biological diversity, ultimately shaping diversification and adaptation of plant lineages in natural and agroecosystems.  Our understanding of the frequency, distribution, and significance of hybridization is rapidly increasing, but the external driving forces that dictate why certain species hybridize, and others do not remain obscure. The physical traits that shape gene flow and trait sharing among species are likely to be among the key factors that directly control hybridization. Gene flow in most plants is mediated by pollinating insects and thus by pollination syndromes, which are suites of floral traits that have evolved …

Cleft Palate And The Coordination Of Wnt Signaling And Pax9 In Murine Palatogenesis, Landon Wyatt

Honors Theses

Cleft palate is a common craniofacial birth defect that arises when the molecular and morphogenetic events guiding secondary palate formation lose coordination during a narrow developmental window. In mice, successful palatogenesis requires the paired palatal shelves to grow vertically, elevate above the tongue, and fuse at the midline; disruption of any of these steps can result in clefting. Two important regulators of this process are canonical Wnt signaling and the transcription factor Pax9, both of which contribute to normal palatal mesenchymal growth and patterning during early development. This paper first examines whether altered Dkk1/Wnt signaling contributes to the Pax9-null palate …

Using The Flexon Approach To Rnai To Identify Essential Genes That Affect Gonadal Development In C. Elegans, Joyce S. Lefevers

Undergraduate Theses

To elucidate the molecular role of essential genes in the gonadal development of Caenorhabditis elegans (C. elegans) it is necessary to utilize specialized molecular techniques such that the phenotypic effects of gene knockdown can be studied while the viability of the organism is preserved. Shaffer and Greenwald (2022) developed the floxed exon (flexon), a tool that improves upon previous approaches to spatiotemporal control of gene expression. The flexon subunit is made up of an artificial exon with a stop cassette flanked by artificial introns which, when inserted into a gene of interest, prevents the expression of that gene. …

Autoantibody Reactivity In Hidradenitis Suppurativa: Characterizing Keratinocyte And Apocrine Gland Targets Across Disease Progression And Anti-Tnf-Α Treatment, Talla Hamouche

Student Theses and Dissertations

Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin disease associated with impaired quality of life, representing one of the highest burdens among dermatological conditions. This debilitating disorder primarily affects apocrine-gland-bearing and flexural skin areas, most commonly the axillae, breast, buttocks, and groin. As lesions recur and new sites emerge, surgical excision does not guarantee prevention of disease reestablishment. Despite its substantial burden, HS remains among the least understood and most treatment-resistant inflammatory diseases. The mechanisms underlying this chronicity and the frequent failure of conventional anti-inflammatory therapies remain unresolved. An underappreciated autoimmune dimension may contribute to HS pathogenesis: the clonal …