Cell and Developmental Biology Commons^™

From Chaos To Clockwork: Investigating The Role Of Circadian Genes In Metabolic Development Of 2nd And 3rd Instar Drosophila Larvae, Elliott R. Ruegsegger, Stephanie Hood, Amy Poe

Biological Sciences Undergraduate Honors Theses

Circadian clocks regulate daily physiological and metabolic rhythms across many organisms. In Drosophila melanogaster, the molecular clock involving period (per) and timeless regulates gene expression across 24-hour cycles. Circadian rhythms are well characterized in adult, mature organisms, but their emergence during early developmental stages remain poorly understood. In D. melanogaster, the circadian regulation of sleep and feeding rhythms emerges during the 3rd instar larval stage. This suggests that the circadian regulation of metabolism may also arise during this stage. Further, the metabolic consequences of circadian clock disruptions during this developmentally rich period remain unclear. This research aimed to …

Identifying The Role Of Human Dna Polymerase Delta During Human Cytomegalovirus Genome Synthesis, Rachel Laree Dansereau

Dartmouth College Master’s Theses

Human cytomegalovirus (HCMV) is a large double stranded DNA virus and member of the Herpesviridae family. Like all herpesviruses, HCMV presents with characteristics of persistent, lifelong infections that transition between lytic and latent states. The replication of the viral genome is traditionally thought to occur by a rolling circle mechanism, but this model is supported by little evidence. It is known that HCMV actively recruits several host proteins to viral replication compartments (RCs), including proteins involved in the DNA damage response (DDR). The exact mechanisms of how these proteins are used and in what ways they help the virus remain …

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 …

Reconstruction Of Fox Transcription Factor-Regulated Subnetworks Mediating Cardiac Progenitor Cell Divisions, Md Rezaul Hasan

All-Inclusive List of Electronic Theses and Dissertations

Congenital heart disease (CHD) is the most common congenital anomaly worldwide, affecting approximately 1% of live births, corresponding to 1.35 million infants born with CHD each year, and remains a leading cause of infant mortality; therefore, it is urgent to understand the genetic and molecular mechanisms underlying CHD for advancing early diagnosis and treatment. Because many aspects of the Drosophila heart formation are highly reminiscent of vertebrate heart development, Drosophila melanogaster serves as a simple yet powerful model system for studying cardiac development and CHD. While at least eight Forkhead box (Fox) transcription factors (TFs) are required for proper cardiac …

Analysis Of The Effects Of Astaxanthin On Human Colorectal Cancer Cells, Kara A. Walters

Theses/Capstones/Creative Projects

Astaxanthin (AXT) is an antioxidant carotenoid that is produced by the microalgae Haemococcus pluvialis. This supplement is best known for its potential health benefits including anti-inflammatory, antitumor, immunomodulatory, anticancer and antidiabetic activities. Astaxanthin is marketed as an oral dietary supplement and is widely used in the nutraceutical industry as well as a coloring agent in the food industry. Since Astaxanthin has been increasingly popular as a dietary supplement, cytotoxicity is relevant to consumer exposure. Obtaining the IC50, the concentration that inhibits 50% of cell growth, is important to find how Astaxanthin may interact with cancer, and this can be found …

Spectral Characterization Of Colorectal Cancer Using Excitation-Scanning Hyperspectral Imaging, Natalie Hadad

Honors Theses

Colorectal cancer is one of the most common and deadly cancers worldwide, with a lifetime risk of approximately one in twenty-three for men and one in twenty-five for women. Although early detection significantly improves survival, current diagnostic approaches such as tissue biopsy are invasive, reliant on subjective interpretation, have extended turnaround times, and risk missing flat or depressed lesions that are more difficult to detect than raised polyps. These limitations highlight the need for objective, minimally invasive technologies capable of detecting early tissue changes. This study investigates excitation-scanning hyperspectral imaging (Ex-HSI) as a label-free optical approach for identifying colorectal cancer–associated …

Developing A Protocol For Non-Cellular Transplantation Of Donor Mitochondria Into Recipient Cells, Andrew Parton

Honors Theses

Tumor innervation has emerged as a critical feature of cancer progression, with increased nerve density correlating with enhanced aggressiveness, metastatic dissemination, and poor clinical outcome. However, the functional contribution of neurons to tumor biology remains incompletely defined. We recently identified the intercellular transfer of mitochondria from neurons to cancer cells as a mechanism that promotes tumor progression. We therefore hypothesized that disruption of this transfer could attenuate tumor aggressivity. To directly investigate this process, we developed an approach to isolate mitochondria from donor cells and transplant them into recipient cancer cells independently of canonical cell-cell interactions. Transferred mitochondria were tracked …

College Of Natural Sciences Spring Newsletter, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

[Page 1] Dean's Message
[Page] 2 Awards & Recognitions // Student Spotlights
[Page] 3 Zhang Named to Landsat Science Team // The Power of Teaching
[Page] 4 “Science as Art” Competition Welcomes High School Artists
[Page] 5 Testing for “Forever Chemicals” in Surface Water // New Faculty Spotlight
[Page] 6 Ambassador Initiated Outreach
[Page] 7 57th Annual Geography Convention
[Page] 8 Twice the Impact on On Call with the Prairie Doc
[Page] 9 Making Staple Foods Healthier // Halaweish & Cole-Dai Retire
[Page] 10 Drone Day 2026
[Page] 11 Student Research, Scholarship, and Creative Activity Day (SRSCAD)
[Page] 12 Ceremony …

Morphological Variation Of Lingual Glands In Wild American Alligator (Alligator Mississippiensis) Populations, Benjamin Angalet

Master's Theses

American alligators (Alligator mississippiensis) inhabit diverse aquatic ecosystems including freshwater wetlands, swamps, and estuarine rivers. As apex predators, their physiological resilience has implications for ecosystem stability and long-term conservation. With projected sea-level rise and increasing saltwater intrusion into coastal freshwater habitats, understanding the osmoregulatory capacity of alligators is increasingly important. Unlike marine-tolerant crocodilians such as the saltwater crocodile (Crocodylus porosus), which possess specialized salt-secreting lingual glands in addition to renal and cloacal mechanisms, the morphology and physiological significance of lingual glands in wild American alligators remain poorly understood. This study examined lingual gland morphology and plasma …

Genetic Screen For Regulators Of Pol4, A Dna Repair Polymerase In Saccharomyces Cerevisiae, Pasang Dolma Sherpa

Theses and Dissertations

In Saccharomyces cerevisiae, DNA polymerase 4 (POL4) is the beta repair polymerase, the product of the POL4 gene, and is involved in base excision repair (BER) and microhomology-mediated end joining (MMEJ). Despite its involvement in these repair pathways and its conservation across eukaryotes, deletion of POL4 shows no detectable phenotype under standard laboratory conditions. I hypothesized that unknown genes act as backup systems, providing redundant activities that allow pol4Δ cells to survive. To test this, a genetic screen for mutants showing synthetic lethality with pol4Δ was implemented. I constructed a strain lacking the POL4 gene and carrying …

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 …

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, …

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 …

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 …

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 …

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 …

Quantification Of Mouse Tracheal Epithelial Cell Differentiation With Cilia Defects, Olivia V. Allen

Honors Thesis

Primary Ciliary Dyskinesia (PCD) is an autosomal recessive disorder that affects 1 in every 7,500 live births. PCD results from motile cilia defects, impairing mucociliary clearance and causing chronic respiratory infections. Our lab studies include three PCD mouse lines — bgh (Spef2), nm1054 (Cfap221), and Cfap54^gt/gt (Cfap54). Prior transcriptomic data led us to hypothesize that PCD mutant mouse tracheal epithelial cells (MTECs) exhibit reduced differentiation into ciliated cells. MTECs from the trachea of the Wild Type (WT) and the PCD mutant mouse lines were cultured at an Air Liquid Interface (ALI) to start …

Optimizing Itpa R178c Assays Via Hplc, Jared J. Reisnouer, Wally D. Pines

2026 Symposium

Two of the major nucleotide bases in DNA and RNA (Adenine and Guanine) are derived from the purine Inosine Monophosphate (IMP). IMP may occasionally form the noncanonical nucleotide Inosine Triphosphate (ITP) within the cell and become incorporated into DNA during replication, leading to potentially lethal errors. To combat this, human cells produce the “housekeeping” enzyme Inosine Triphosphatase (ITPA) to revert ITP to IMP. A mutation of this protein that replaces the 178th amino acid Arginine with Cysteine (R178C) is associated with a fatal infantile encephalopathy. Previous assessments of enzyme-substrate binding and catalysis for ITPA variants have been run at a …

Transgenic Plant Cells For The Cost-Effective Production Of Pharmaceutical Proteins, Maria Gambaro

Create@State

Plant-based systems are becoming an important method for producing pharmaceutical proteins because they can be more cost-effective, and safer compared to traditional production methods which commonly use mammalian cells. This project aims to develop a transgenic plant cell system that can produce a pharmaceutical protein using molecular cloning techniques. A transgenic plant cell has the DNA of another plant integrated into its genome, altering its gene expression to produce different proteins. To begin, a plasmid carrying the gene of interest and the DNA components needed for expression will be designed. The plasmid will then be used to introduce the gene …