Cell and Developmental Biology Commons^™

Pi3kδ Inhibition Alters Cd8 T Cell Differentiation And Reprograms The Tumor Microenvironment Following Adoptive Immunotherapy, Alexandrea Joy Turnquist

Dartmouth College Ph.D Dissertations

T cell exhaustion remains a significant barrier to effective adoptive cell therapy in solid tumors. Here, we demonstrate that in vitro treatment with the PI3Kδ inhibitor CAL-101 generates T cells with enhanced stemness and metabolic fitness, though the stemness of these cells is not dependent on HIF-1α -dependent mechanisms. These cells show increased mitochondrial dependence and spare respiratory capacity while maintaining normal basal metabolism. Under chronic antigen stimulation, CAL-101-treated T cells, including human T cells, resist terminal exhaustion and maintain stem-like properties. Using single-cell RNA sequencing and spatial transcriptomics of B16 melanoma tumors, we found that CAL-101-treated T cells preferentially …

Investigating The Role Of Gαf In Sperm Storage In The Spermathecae Of Female Drosophila Melanogaster, Aileen Liu

Holster Scholar Projects

Reproductive secretory cells are essential for fertility and have been implicated in diseases such as high-grade serous cancer, yet the molecular mechanisms governing their function remain poorly understood. Using genetic tools available in Drosophila melanogaster, we investigated whether Gαf contributes to reproductive secretory-cell function by examining its role in sperm storage. Gαf is highly expressed in these cells, suggesting a potential role in secretory cell function. Tissue-specific RNAi, trans-heterozygous mutants, and tissue-specific rescue were utilized to examine the role of Gαf in sperm storage. Gαf knockdown consistently reduced sperm storage, supporting a role for Gαf in maintaining normal sperm …

Validation Of Next‑Generation Sequencing‑Derived Circulating Mrna Variants As Potential Diagnostic Tools In Hepatocellular Carcinoma And Cholangiocarcinoma, Daniel Zezulinski, Maarouf A. Hoteit, David E. Kaplan, Tingting Zhan, Cataldo Doria, Timothy M. Block, Aejaz Sayeed

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Liquid biopsy can transform oncology practice through early detection and real‑time monitoring of cancer progression and response to treatment. Circulating cell‑free tumor RNA offers promise as a novel and emerging alternative to circulating cell‑free tumor DNA for detecting the presence and understanding the biology of liver tumors. Both circulating DNA and RNA, which predominantly reside in extracellular vesicles, carry evidence of vital germline and somatic mutations. High impact single nucleotide changes, insertions and deletions in circulating RNA (ctRNA) serve a key role in cancer development and progression. Tumor cells exploit the RNA splicing machinery to induce structural and functional changes …

Ddrr Acts As A Dna Damage-Induced Cell Division Inhibitor In Acinetobacter Baumannii, Christian P. Lowe, Deborah Cook, Lily Hoard, Mckinnley Martin, Janelle M. Hare

Acinetobacter baumannii DNA Damage Database

An article titled, "DdrR acts as a DNA damage-induced cell division inhibitor in Acinetobacter baumannii" published in the Journal of Bacteriology on September 9, 2026.

Charge Modulation Of Peptide/Nucleic Acid Complexes: An Anionic Additive Enhances Gene Silencing And Crispr/Cas9 Editing By Promoting Intracellular Nucleic Acid Release, Abdulelah Alhazza, Sorour Khayyatnejad Shoushtari, Hasan Uludag, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Introduction: Small interfering RNA (siRNA) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated Protein 9 (Cas9) complexes are effective approaches to temporarily downregulate protein expression via post-transcription RNA interference or permanently altering protein expression via editing genomic DNA, respectively. However, the efficient delivery of these mediators to targeted cells has been challenging, largely due to their anionic and hydrophilic nature, which hinders their interaction with the cell membrane and cellular internalization. Cell-penetrating peptides (CPPs) exhibit dual characteristics as a carrier for nucleic acid delivery, where positively charged components bind to the negatively charged nucleic acid, and the hydrophobic components …

Architects Of Mrna Fate: Molecular And Cellular Control Of P-Body Organization In The Drosophilia Melanogaster Female Germline, Samantha Milano

Dissertations, Theses, and Capstone Projects

Processing bodies (P-bodies) are cytoplasmic ribonucleoprotein condensates that regulate mRNA storage, translational repression, and decay. While the biochemical principles governing condensate assembly have been extensively studied in vitro, how P-body organization is established and dynamically regulated in vivo to control specific mRNA populations remains poorly understood. This dissertation investigated the molecular and cellular mechanisms that govern P-body architecture and function in the Drosophila melanogaster female germline. First, I identified the conserved LSm protein Trailer Hitch (Tral) as a central organizer of P-body architecture. Using quantitative confocal and super-resolution microscopy combined with chemical perturbations, I showed that Tral coordinates the …

Data Curation And Integration For Cancer Cell Line Pharmacogenomics Analysis, Meric Kinali

Graduate Masters Theses

Cancer cell lines are essential resources for connecting genomic and molecular features with drug response and identifying biomarkers. Therefore, large-scale cancer cell line resources have been growing, but this introduces challenges such as data standardization, consistent annotation, matching identifiers, cross-database integration, and a reproducible computational framework. CellMiner Cross Database (CellMinerCDB) integrates pharmacogenomic datasets from multiple resources and provides a standardized analysis of cell lines across datasets. This thesis examines cancer cell line cross-databases and their importance in pharmacogenomics, with a particular focus on CellMinerCDB. As part of this work, I developed an R package for the gCSI (Genentech Cell Line …

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 …

Urinary Collagen As An Indicator Of Prostate Fibrosis In Lower Urinary Tract Dysfunction, Claweens Quetant

Graduate Masters Theses

Lower urinary tract dysfunction (LUTD) is a progressive disorder that affects millions of men over the age of 50 years old. LUTD manifests as urgency, nocturia, urinary frequency, weak urinary stream, and incomplete bladder emptying (Egan, 2016). The current treatment for LUTD doesn’t always yield the desired results due to several issues. In this thesis, we aim to address the lack of suitable tools for detecting prostatic collagenization and to assess whether urine could serve as a substrate for detecting pro-fibrotic proteins associated with moderate-to-high AUASI scores. We used whole urine from 2 different cohorts, the Boston and the LURN …

Crosstalk Between Upr And Mitochondria: The Triad Of Er-Mitochondria Contacts, Ca²⁺, And Ros, Ester Zito, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endoplasmic reticulum (ER) stress is triggered by several cellular perturbations causing protein misfolding, and activates the unfolded protein response (UPR), an initially adaptive signaling network that aims to restore ER and cellular homeostasis. Growing evidence indicates that UPR signaling extends beyond ER proteostasis, influencing mitochondrial function and bioenergetics through ER-mitochondria contact sites (ERMCs). The CHOP-ERO1A-IP3R axis has a primary role in recruiting mitochondria to adaptive UPR. However, its sustained activation renders UPR signaling maladaptive, leading to mitochondrial dysfunction through both outer mitochondrial membrane permeabilization (OMMP) and mitochondrial permeability transition pore (mPTP) opening, ultimately contributing to irreversible cell injury and disease …

The Role Of Seed Mix Characteristics And Soil Amendments During Post-Agricultural Prairie Restoration, Valerie N. Thurston, Michaela J. Woods, Madelaine Gregory, Mary C. Lloyd, Ryan W. Mcewan

Biology Faculty Publications

Introduction: Prairie restoration on degraded lands may be influenced by seed mix characteristics, including species richness and legume establishment. Soil amendments may facilitate restoration; however, the practical usefulness of techniques such as applications of whole soil and leaf mulch remains relatively unclear.

Objectives: We assessed whether increasing species richness and legume content in seed mixes enhances prairie restoration success and examined how soil amendments interact with seed mix composition to influence cover, species richness, diversity, and legume establishment.

Methods: We conducted a field experiment on a 12-ha post-agricultural site in Ohio, U.S.A. Twenty 50 × 50 m plots received one …

Three-Dimensional Cell And Nuclear Geometries Inform Tissue Level Fluid Mechanics During Epithelial Remodeling, Liam Joseph Russell

Electronic Theses and Dissertations

During epithelial remodeling, mechanical and molecular programs must coordinate to drive the cell shape changes that enable new tissue topologies. Dynamic morphogenesis requires epithelia to preferentially exhibit solid- or fluidlike properties depending on developmental and biophysical constraints. Convergent extension in the Drosophila germband epithelium is one such remodeling event, during which the lateral ectoderm lengthens by two-fold along the primary body axis while concomitantly shortening orthogonally. This process is an incredibly dynamic and attractable system for studying tissue morphogenesis mechanics in vivo.

Germband extension is driven by oriented cell intercalation through T1 transitions, where cells directionally interdigitate with one another …

Investigating Caveolar Systems: Spatiotemporal Quantification Of Caveolin-1 And The Mechanotransducive Function Of Ehd2, Jasper Stanae Farrington

Electronic Theses and Dissertations

Caveolae are 50-100nm cholesterol rich flask shaped invaginations found in many differentiated cells. Namely, these structures have been seen to be abundant in endothelial cells where they are involved in many signaling contexts. However, under mechanical stress, the characteristics of caveolae alter, flattening to increase membrane compliance, while displaced proteins can shift from structural roles to mechanosensitive signaling functions. Caveolin-1 (Cav1) is the principal protein required for Caveolar formation while Eps15 Homology Domain Containing Protein 2 (EHD2) is a membrane ATPase that acts to stabilize caveolae at the surface. Despite their emerging importance, understanding the organization and dynamic regulation of …

Exploring Foundations Of Animal Host-Microbe Interactions In A Freshwater Sponge, Jacob S. Pawley

Electronic Theses and Dissertations

The most ancient eukaryotic immune defense mechanisms evolved in unicellular species. Multicellular eukaryotes, however, expanded these mechanisms to meet challenges unique to multicellular life, including barrier formation, long-distance cell signaling, and coordinated responses that eliminate microbial threats while minimizing damage to the host. As such, animal immune signaling pathways are exceptionally intricate and diverse. Though, most of what is understood about animal host–microbe interactions stems from a small handful of model systems. Here, I evaluate host–microbe interactions and innate immunity in sponges using the highly tractable freshwater sponge, Ephydatia muelleri. I report the discovery of an external host-derived matrix …

Antimicrobial Responses Of Staphylococcus Aureus In Simulated Spaceflight Conditions, Mikayla Dutkiewicz, Yegor Bushnev

Discovery Day - Daytona Beach

Microbial persistence in confined environments, such as spacecraft, can pose challenges to astronaut health and habitat maintenance. This project investigates Staphylococcus aureus, a Gram-positive bacterium commonly associated with human microbiota and opportunistic infections, in spaceflight-relevant environmental conditions. Further, this project will assess the influence of the antimicrobial/antioxidant compound quercetin to assess its effects on bacterial growth and virulence under standard Earth gravity and simulated International Space Station (ISS) conditions. This approach will assess whether spaceflight-relevant stressors, including microgravity and radiation, alter treatment efficacy by influencing microbial physiology and antimicrobial susceptibility. Data collection and analysis are ongoing, and results are expected …

Tardigrade Bio-Exploration Reproduction Research Payload, Natalie Brattain, Chloe Nissen, Kylie Nager, Peter Ulrich, Enoch Tonkine

Discovery Day - Daytona Beach

The Tardigrade Bio-ExplorAtion Reproduction Research Payload (tBEARR) is an external International Space Station (ISS) standardized laboratory payload module mission under development by the Embry-Riddle Orbital Research Association (ERORA), an undergraduate research organization at Embry-Riddle Aeronautical University (ERAU) in Daytona Beach, Florida. As a club-driven mission, tBEARR provides undergraduate students with hands-on experience across all phases of space research, including payload design, biological experimentation, systems integration, and mission operations. The mission is supported by a biology research team focused on stress-response biology, experimental design, and biological validation throughout ground testing, high-altitude balloon flights, and orbital operations.   The primary objective of tBEARR …

Apical-Out Lung Organoids: A Platform For Spaceflight And Cf Research, Valeria Jimenez, Ally Schwennesen

Discovery Day - Daytona Beach

A genetic condition known as cystic fibrosis (CF) is brought on by mutations in the CFTR gene, which results in chronic lung inflammation and impaired chloride ion transport. CF bronchial epithelial cells enable direct comparison of disease pathology, while normal human bronchial epithelial (NHBE) cells offer an essential model for researching airway physiology. Realistic modeling of respiratory tissue and its reaction to environmental stressors like microgravity is made possible by the creation of 3D lung organoids from these cells. In this project, we developed apical-out organoids, which expose the apical surface of epithelial cells to the external environment. These organoids …

Interplay Between Patterning And Morphogenesis During Zebrafish Embryonic Development, Chia-Teng Chang

Arts & Sciences Graduate Student Theses and Dissertations

Patterning and morphogenesis occur concurrently during embryonic development. In many contexts, both processes are regulated by morphogen signaling: morphogens specify spatially organized cell identities while also influencing the cell behaviors that shape tissues. This creates a reciprocal problem. Morphogen signaling can affect how cells move, while cell movement can change how cells experience and interpret morphogen signals. This dissertation investigates this reciprocal problem during zebrafish gastrulation and neurulation. First, it examines how the ventral-to-dorsal bone morphogenetic protein (BMP) activity gradient regulates germ-layer morphogenesis during gastrulation. BMP signaling is known to pattern dorsal–ventral cell fate and regulate mesodermal convergence and extension …

Assessing Non-Thermal Plasma In Cutaneous Regeneration, Arden Rodriguez, Meliah Martin, Graeme Grainger, Arineh Shahbazi

Discovery Day - Daytona Beach

Chronic and acute wounds remain a significant clinical challenge, particularly in austere and resource-limited environments where access to advanced care is restricted. Non-Thermal Plasma (NTP) has emerged as a promising, non-invasive modality with reported antimicrobial and regenerative properties; however, its mechanisms of action and effects on human skin tissue require further characterization. The scope of this project is to engineer and utilize a 3D human skin epithelial model to evaluate the effects of NTP on wound healing. We will first build a 3D epithelial tissue model that will simulate human skin, followed by modeling and evaluation of wound pathology and …

The Osteocyte-Osteoblast Network Requires Dynamic Mechanical Loading For Key Functions, Kevin Kowalski

Discovery Day - Daytona Beach

Spaceflight investigations have demonstrated that reduction in gravity-induced loading regimes is detrimental to maintenance Earth-normal bone and marrow. Mechanistically, however, there are still gaps in knowledge about how the reduction in gravity influences the different niches within the tissue. For example, cortical bone is a stable semi-solid structure that allows for only minor deformations before failure, while marrow is a viscous hydrogel-like material that can resist significant fluidic and compressive forces. We hypothesize that maintenance of different niches within the bone microenvironment are dependent on different loading regimes, and that the collective impact if gravity-induced loading needs to be considered …