Life Sciences Commons^™

Targeting Nonsense-Mediated Rna Decay In Splicing Factor Mutant Myeloid Malignancies, Claudia Cabrera

Arts & Sciences Graduate Student Theses and Dissertations

Approximately 50% of patients with myelodysplastic syndromes (MDS) (which frequently progresses to secondary acute myeloid leukemia [AML]), 60% of chronic myelomonocytic leukemia (CMML) and 20% of de novo AML harbor heterozygous somatic mutations in spliceosome genes. We and others have shown that mutations in spliceosome genes U2AF1, SF3B1, SRSF2 and ZRSR2 cause alterations in RNA splicing, leading to production of numerous aberrant RNAs. Interestingly, spliceosome mutant cells are more sensitive to genetic alterations or drugs that further perturb RNA splicing, compared to wild-type cells. The sensitivity of spliceosome mutant cells to further perturbations in RNA splicing raises the possibility that …

Understanding Loss Of Beta-Cell Identity And Progression Of Diabetes In Polygenic Mouse Models Of T2dm, Sumitkumar Patel

Arts & Sciences Graduate Student Theses and Dissertations

Type 2 diabetes (T2DM) is caused by the complex interaction of multiple genes and environmental factors. T2DM is characterized by hyperglycemia, insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing β-cells, recent studies indicate that β cell apoptosis rates are relatively low in diabetes. In this dissertation, I investigated β-cell failure in diabetes using KK and KKAy mouse models of polygenic T2DM, which spontaneously develop hyperglycemia, glucose intolerance, glucosuria, impaired insulin secretion and insulin resistance. I found that β-cell failure in KK …

Performative Biomechanics : Evolving Buildings Into Inhabitable Organisms, Josh Lopez

Bachelor of Architecture Theses - 5th Year

There has always been a connection between biology and architecture. Michael Pawlyn, in Biomimicry in Architecture, coined “biomechanical designs” to describe structural techniques derived from creatures. This study investigates chitin-based creatures. Crustaceans, insects, and microscopic organisms all have exoskeletons in nature. With a focus on crabs, other crustaceans and bugs, this study examines and evaluates the formal characteristics of chitin-based organisms. The architectural creations of OXMAN, NOX, which was founded by Lars Spuybroek; and Lebbeus Woods are among those that are analyzed and studied due to their inspiration from living things. They follow functional effectiveness in nature, which is why …

Progressive Multifocal Leukoencephalopathy In Chimeric Antigen Receptor T-Cell Therapy Recipients: A Case Study, Michelly Abreu, Chirag B Patel, Krina Patel, Fareed Khawaja, Sudhakar Tummala

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy modality that has shown remarkable response rates in refractory hematologic malignancies, including multiple myeloma (MM). Cytokine release syndrome (CRS) and neurotoxicity are well-described side effects of this therapy. CAR T-cell therapy recipients are also at increased risk for infections due to immune dysfunction, history of multiple lines of therapy, history of lymphodepleting chemotherapy prior to cell infusion, and prolonged B-cell aplasia. Progressive multifocal leukoencephalopathy (PML) is an opportunistic disease of the central nervous system caused by the reactivation of JC virus (JCV) in the setting of immunosuppression, which leads to …

Axl Promotes Inflammatory Breast Cancer Progression By Regulating Immunosuppressive Macrophage Polarization, Lan T H Phi, Yating Cheng, Yohei Funakoshi, Francois Bertucci, Pascal Finetti, Steven J Van Laere, Fang Zou, James P Long, Suguru Ogata, Savitri Krishnamurthy, James M Reuben, Jason M Foulks, Steven L Warner, Jennifer M Rosenbluth, Anil K Sood, Debu Tripathy, Naoto T Ueno, Xiaoping Wang

Faculty, Staff and Student Publications

Background: Tumor-associated macrophages (TAMs) are key promoters of inflammatory breast cancer (IBC), the most aggressive form of breast cancer. The receptor tyrosine kinase AXL is highly expressed in various cancer types, including IBC, but its role in TAMs remains unexplored.

Methods: We examined the effects of AXL inhibitor TP-0903 on tumor growth and tumor microenvironment (TME) component M2 macrophages (CD206+) in IBC and triple-negative breast cancer mouse models using flow cytometry and immunohistochemical staining. Additionally, we knocked out AXL expression in human THP-1 monocytes and evaluated the effect of AXL signaling on immunosuppressive M2 macrophage polarization and IBC cell growth …

Effects Of Angptl3 Deficiency On The Regulation Of Hepatic Lipoprotein Production And Lipid Metabolism, Kendall Helene Burks

Arts & Sciences Graduate Student Theses and Dissertations

Cardiovascular disease is the leading cause of death worldwide. A major treatment goal is to lower plasma lipids, especially low-density lipoprotein cholesterol (LDL), the cardinal risk factor for coronary artery disease (CAD). Patients with familial hypercholesterolemia (FH) experience early-onset CAD due to extremely high LDL. Underdiagnosis and undertreatment of FH are exacerbated by limited therapeutic options. However, one strategy has successfully lowered LDL in FH patients: Inhibition of the hepatically secreted protein Angiopoietin-like protein 3 (ANGPTL3). Despite promising clinical data, the mechanism by which ANGPTL3 inhibition lowers LDL has not been fully described. Although ANGPTL3 has been shown to modulate …

Characterizing Piezo1 Mechanotransduction In Articular Chondrocytes, Jaquelin Marlen Garcia Castorena

Arts & Sciences Graduate Student Theses and Dissertations

Osteoarthritis (OA) is the most common degenerative joint disease, affecting more than 350 million people worldwide. Along with inflammation and pain, a hallmark of OA is the degradation of articular cartilage (AC), an avascular and aneural tissue that coats and facilitates the bending of diarthrodial joints. AC withstands millions of cyclic mechanical loads annually, and chondrocytes, the only resident cells in the tissue, sense these loads through mechanically gated ion channels, including Transient Receptor Potential Vanilloid 4 (TRPV4), PIEZO1 and PIEZO2. PIEZO1 is a highly expressed calcium ion channel in chondrocytes that can be activated through mechanical loading or chemically …

Functional Diversification Of Rice Ago1 Proteins, Rachel Elie Jouni

Arts & Sciences Graduate Student Theses and Dissertations

Global demand for food is outpacing gains from conventional plant breeding. Scientists have turned to molecular crop breeding techniques to increase crop output and mitigate global hunger; however, a common setback in this process is the pleiotropic effects of target genes. We need to develop strategies to specifically modulate desired traits without incurring undesired penalties. Natural evolution frequently balances such tradeoffs through extensive regulation, which we can leverage to produce more specific results. Reproductive development is an important target of breeding efforts due to its direct effect on yield. Rice, a major staple food crop for half the world’s population, …

Investigating The Roles Of Sox10 And Etv4 In Melanocyte And Melanoma Development, Catherine Marie Newsom-Stewart

Arts & Sciences Graduate Student Theses and Dissertations

The neural crest is a transient, multipotent cell population unique to vertebrates that gives rise to diverse lineages, including craniofacial cartilage, peripheral neurons, glia, and pigment-producing melanocytes. Proper specification and differentiation of neural crest derivatives are orchestrated by tightly regulated gene regulatory networks, and disruption of these developmental programs can lead to congenital disorders and malignancies. Melanocytes, derived from the neural crest, are best known for their role in skin pigmentation but also contribute to homeostasis and specialized functions in the eye, ear, and heart. These cells produce melanin to protect tissues from ultraviolet radiation and oxidative damage, and they …

Lifespan Reference Curves For Harmonizing Multi-Site Regional Brain White Matter Metrics From Diffusion Mri, Alyssa H. Zhu, Talia M. Nir, Shayan Javid, Julio E. Villalón-Reina, Amanda L. Rodrigue, Lachlan T. Strike, Greig I. De Zubicaray, Katie L. Mcmahon, Margaret J. Wright, John Blangero

School of Medicine Publications

Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3–95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data …

Treatment Wastewater Of Oil Refinery By Fe2o3 Nps Produce By The Novel Alishewanella Jeotgali Strain Haq8., Hawraa Qays Al-Assdy, Wijdan Hussein Al-Tamimi, Asia Fadhile Almansoory

Karbala International Journal of Modern Science

Metal oxide nanoparticles like iron oxide (Fe₂O₃) exhibit strong reactivity and photolytic features in wastewater treatment and serve as an effective adsorbent for water purification due to its substantial surface area and affinity for different functionalized groups. Iron oxide nanoparticles) IONPs) are currently applied to treat oil-contaminated water. Fe₂O₃NPs were produced using an extracellular approach utilizing the Alishewanella jeotgali strain HAQ8. IONPs were characterized using UV-vis, FT-IR, XRD, AFM, SEM-EDX, and Zeta potential. λ max for the synthesized nanoparticles observed at (358) nm. The bands at 485 cm⁻¹ in the FT-IR spectrum confirmed the formation of …

Quantifying Dna Methylation In Response To Drought Stress In Silver Firs (Abies Alba), Julia K. Brandfonbrener

Biology Honors Projects

As future droughts are expected to increase in duration and severity due to climate change, forest managers may need to evaluate which coniferous species are the most resilient in drought events. Drought stress induces changes in physiology, including decreases in water potential, stomatal closure, pigment degradation, and leaf senescence (Jongdee et al., 2002, Munné-Bosch & Alegre, 2004, Heitholt et al., 1991). These physiological changes are associated with epigenetic regulation of gene expression in response to abiotic stressors (Alongi et al. 2025) and have been highly studied in crop plants and Arabidopsis. This project examines the photosynthetic and epigenetic response …

Digitization And Archival Of Insect Collections: Literature Review, Rebekah Rogers

Department of Entomology: Distance Master of Science Projects

A slide presentation discussing how and why digitization has become a key component in the curation and care of natural history collections.

Understanding Potential Profitability Estimates For Western Kentucky Grain Production, Austin Randolph, Naveen Musunuru

Honors College Theses

Profitability remains a persistent challenge for grain farmers across the United States and globally. Without profitability, the continued operation of any grain farm becomes unsustainable. For grain farmers, profitability is not merely a financial goal but a crucial determinant of their livelihood. However, many grain producers face a significant obstacle: a lack of reliable tools to predict profitability and plan for the next season or make adjustments to existing operations. While budgets can offer a framework and tentative guidelines for farmers to follow, fluctuations in market prices can ultimately undermine these financial plans. The objective of this project is to …

Novel Combination Therapies For Estrogen Receptor-Positive Breast Cancer Driven By Rational Molecular Mechanisms, Anneka Lila Johnson

Dartmouth College Ph.D Dissertations

Breast cancer (BC) is the most common non-keratinocyte cancer diagnosed in women in the United States with approximately 300,000 new cases diagnosed each year. Despite a myriad of treatment options, BC remains the second-most deadly cancer. Estrogen receptor-positive (ER+) BC comprises 60-70% of BC diagnoses and is treated with endocrine therapies that limit ER signaling. Despite endocrine therapy options, ~1/3 of patients experience recurrence within 10-20 years of diagnosis. Novel therapeutic strategies are required to limit BC recurrence-related morbidity and mortality.

Radiotherapy is used as an adjuvant treatment for ER+ BC patients prior to the use of endocrine therapy. Radiation …

05.05.2025 Ored Connect, Liz Williamson

ORED Newsletter

Research Showcase Photos

Showcase Raffle Winners

Chancellor's Award for Research and Creative Scholarship

Video of the ORED website

Protocol For A Randomized Controlled Trial To Determine If Biomarkers Predict Response To A Pediatric Chronic Pain Symptom Management Program, Rona L Levy, Tasha B Murphy, Margaret M Heitkemper, Miranda A L Van Tilburg, Ann R Mcmeans, Jocelyn Chang, Cynthia Boutte, Katherine Lamparyk, Bruno P Chumpitazi, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Background/Objectives: Disorders of gut-brain interaction (DGBI), characterized by chronic abdominal pain and significant disability, affect 15-20% of children and adults and continue into adulthood in ~60% of cases. Costs for adults reach USD 30 billion per year, yet effective management strategies are elusive. Studies support using cognitive behavioral therapy (CBT), but abdominal pain only improves in ~40% of patients. Dietary management (low FODMAP diet; LFD) has also shown promise but it is effective in only a similar percentage of patients. Studies suggest that biologic factors (biomarkers) contribute to CBT response. Similarly, gut microbiome composition appears to influence abdominal pain …

Language Mapping During Awake Brain Surgery In A Deaf Patient With A Brain Tumor: Illustrative Case, Ene Chibawanye I, Elizabeth Silva, Kyle Noll, Mariana Bradshaw, Katherine Connelly, Ho-Ling Liu, Ravi Tummala, David Ferson, Frederick F Lang, Vinodh A Kumar

Faculty, Staff and Student Publications

Background: Signed language integrates complex sensorimotor processes involving visual and motor networks. The contribution of language regions such as Broca's and Wernicke's areas during signing is not well established. Here, the authors report the case of a 45-year-old right-handed male with congenital deafness, who communicates using American Sign Language (ASL) and Signed English, presenting with focal seizures. Imaging showed a diffuse infiltrative glioma in the right cerebral hemisphere.

Observations: Remarkably, preoperative functional MRI language activations were bihemispheric and overlapped for both traditional language paradigms and sign paradigms, suggesting that the same cortical regions of the brain are used for language …

Mitochondrial Network Expansion And Loss During Oligodendrocyte Life And Death, Xhoela Bame

Dartmouth College Ph.D Dissertations

Oligodendrocytes are the myelinating cells of the central nervous system, known for modulating signal transmission, refining neural circuits, and providing metabolic support to axons. Oligodendrocytes are generated throughout life from oligodendrocyte precursor cells (OPCs) and are damaged or lost in demyelinating and neurodegenerative diseases and age-related pathologies. Thus, understanding the cellular checkpoints that occur during the generation and degeneration of oligodendrocytes is crucial for maintaining their population in health and recovering it in disease and aging.

Using high-resolution optical imaging, I have discovered a dynamic redistribution and subcellular partitioning of mitochondria during oligodendrogenesis. Mitochondria transiently expanded towards the differentiating OPC …

Acquisition Algorithms For Protein Mass Spectrometry And Their Application To Clinical Proteomics, Nathan Wamsley

Arts & Sciences Graduate Student Theses and Dissertations

Bottom-up protein mass spectrometry aims for the identification and quantification of protein species by proxy of their proteolytic peptides. This dissertation presents methodological advances in three areas of protein mass spectrometry: acquisition methods, clinical appli- cations, and data analysis algorithms. The second chapter presents an optimized internal standard-triggered parallel reaction monitoring (OIS-PRM) method and demonstrates its application to study prognostic biomarkers in head and neck squamous cell carcinoma (HN- SCC). OIS-PRM uses intelligent scan scheduling and real-time monitoring of peptide elution profiles to reduce cycle-times and improve quantitative precision and accuracy. The assay measured NRF2 activation in both cell lines …

Proteogenomic Analysis To Inform Causal Gene Prioritization For Human Disease, Daniel Western

Arts & Sciences Graduate Student Theses and Dissertations

Genome-wide association studies (GWAS) have been key in expanding our understanding of the genetic contributions to common diseases. However, these genetic associations frequently fail to clarify causal disease mechanisms, as they often fall in non-coding regions and are difficult to interpret. One solution is to perform a GWAS for the levels of a cellular trait, known as quantitative trait locus (QTL) mapping. Through methods such as colocalization, Mendelian Randomization, and transcriptome/proteome-wide association studies, the QTL variants can be compared to disease GWAS, identifying shared variation between cellular and disease traits. We can then prioritize cellular traits as potential causative, targetable …

Examing The Role Of Complement Signaling In Viral Neuroinflammatory Responses, Marlene Kanmogne

Arts & Sciences Graduate Student Theses and Dissertations

The complement system is an ancient pathway that serves dual roles as a key regulator of neuroinflammation and a critical regulator of neural networks. Few studies have addressed how these two pathways may interact during infection of the central nervous system. While some components of complement are expressed in the healthy developing brain, complement component 3a receptor (C3aR) is a G protein coupled receptor that is expressed by astrocytes, microglia and infiltrating immune cells during inflammatory states. We previously found that C3aR is required for engulfment of synaptic material by activated microglia during neuroinvasive viral infection. Here, we used a …

Mutant-Specific Analysis Of Tumor Cell Heterogeneity In Glioblastoma, Patrick Desouza

Arts & Sciences Graduate Student Theses and Dissertations

Glioblastoma (GBM) is an aggressive brain tumor driven by the interplay between tumor cell-intrinsic and -extrinsic heterogeneity, enabling rapid evolution. To investigate how canonical GBM mutations promote functional plasticity, we developed an isogenic human neural stem cell (NSC) model of GBM by sequential addition of TERT promoter, TP53, and PDGFRA point mutations. TP53 loss-of-function increased TERT expression during serial mutagenesis, but only triple mutant NSCs reliably formed lethal brain tumors in vivo that recapitulate GBM. Tumor cell evolution triggered stress-related metabolic changes and transitioned toward a neuronal progenitor network driven by transcription factor INSM1. INSM1 is highly expressed in human …

Mechanisms Of Protective Humoral Immunity And Pathogenesis In Alphavirus Infection, Natasha Monir Kafai

Arts & Sciences Graduate Student Theses and Dissertations

Alphaviruses are enveloped, mosquito-transmitted, positive-sense RNA viruses of the Togaviridae family classified into Old and New World groups based on endemic regions and human disease characteristics. Old World alphaviruses, including chikungunya virus preferentially cause arthritogenic disease, whereas New World viruses like Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV), and Western equine encephalitis virus (WEEV) can cause neurological disease. Since the 1920s, VEEV has been responsible for major periodic outbreaks affecting hundreds of thousands of humans and equines in South and Central America. Expansion of mosquito vectors raises concern for possible VEEV reemergence. In addition, VEEV is a …

Birds Of A Feather: An Integrated Outdoor-Based Bird Study P-3 Curriculum Guide, Erin A. Buzza

Masters Theses/Capstone Projects

In a post-pandemic world that places technology at the at the forefront, educators are searching for ways to help students connect with the natural world. This project aids teachers in tackling this challenge by using the study of birds as a motivation to engage students with the outdoors and local wildlife. To demonstrate how ornithology topics can be used as an integrated thematic unit, research regarding components of ecological literacy is presented. They include nature-based learning, outdoor learning, environmental education, and wildlife education. In addition to these pedagogies, the benefits of incorporating interdisciplinary learning within the classroom are also provided …

The Impact Of Insufficient Sleep On The Serial Reproduction Of Information, David L. Dickinson, Sean P. A. Drummond

ESI Publications

Story retelling is an important form of communication, cultural practice, and message transmission. Insufficient sleep is known to affect relevant cognitive skill areas necessary for story retelling or transmission fidelity. We conducted a preregistered randomized cross-over study on n = 155 young adults with exogenously assigned nightly sleep levels experienced in their at-home environments. A serial story reproduction task was administered online, and chains of up to three retells of a given story involved varied numbers of sleep restricted (SR) versus well-rested (WR) retellers. While story content decayed with each retell, group-level analysis showed that additional SR retellers in a …

Evaluation Of Phenotypic Antimicrobial Resistance From Bacterial Pathogen Isolates In Bison, Aleena M. Kallan

Honors Capstones

Bison, the American buffalo, are increasingly utilized for food consumption due to their high protein content. Shiga toxin-producing Escherichia coli (STEC) is an important food-borne pathogen that leads to severe clinical infections and becomes antimicrobial-resistant (AMR). Specifically, fluoroquinolone antibiotics can complicate human treatment when infected with resistant STEC. This study aims to determine the presence of STEC in bison reservoirs and their antimicrobial resistance. Fecal samples (n=320) from bison herds were collected, followed by specific culture-based isolation for STEC. Polymerase chain reaction (PCR) was employed for pathogen confirmation, with 25.6% prevalence. PCR targeting gene, gyrA (resistant to fluoroquinolone), was tested …

Endemism Shapes Viral Ecology And Evolution In Globally Distributed Hydrothermal Vent Ecosystems, Marguerite V. Langwig, Faith Koester, Cody Martin, Zhichao Zhou, Samantha B. Joye, Anna-Louise Reysenbach, Karthik Anantharaman

Biology Faculty Publications and Presentations

Viruses are ubiquitous in deep-sea hydrothermal vents, where they influence microbial communities and biogeochemistry. Yet, viral ecology and evolution remain understudied in these environments. Here, we identify 49,962 viruses from 52 globally distributed hydrothermal vent samples (10 plume, 40 deposit, and 2 diffuse flow metagenomes), and reconstruct 5708 viral metagenome-assembled genomes, the majority of which were bacteriophages. Hydrothermal viruses were largely endemic, however, some viruses were shared between geographically separated vents, predominantly between the Lau Basin and Brothers Volcano in the Pacific Ocean. Geographically distant viruses shared proteins related to core functions such as structural proteins, and rarely, proteins of …

Genomic Structure Among Populations Of A Regionally Rare Perennial Plant Indicates The Need For Reevaluation Of Management Units, Cheyenne Moore, Angela J. Mcdonnell, Scott Schuette, Christopher T. Martine

Faculty Journal Articles

Conservation of rare species often relies on the delineation of management units and genomic tools can now be applied for this purpose. However, this is not as common on a local scale, where populations are often small and fragmented, despite the utility of informing conservation and management practice at the regional level. We use a genotyping by sequencing (GBS) approach to assess the perennial riparian plant species Baptisia australis (Fabaceae) in Pennsylvania, where the taxon is at the edge of its natural distribution and considered threatened. In this system, we investigate whether sampled subpopulations exhibit genetic structure. We find that …

Rapid Identification Of Ambystoma Mexicanum Genotype Using Pcr Techniques, Elizabeth C. Dean

Undergraduate Honors Thesis Projects

Ambystoma mexicanum is an aquatic salamander species, commonly known as the axolotl, native to Mexico that is widely researched all over the world. In the wild, these salamanders have brown/black colored skin due to the presence of melanophores and xanthophores with shiny spots due to iridophores. In captivity, however, there are multiple different color morphs (phenotypes) of axolotls including leucistic, melanistic, and copper. Melanoid axolotls have black skin made by mostly melanophores, little xanthophores, and no iridophores. Melanistic genotypes such as melanoid and wild type color morphs are thought to be controlled by a single gene called Leukocyte Tyrosine Kinase …