Cell and Developmental Biology Commons^™

Modulation Of Redox-Sensitive Cardiac Ion Channels, Rawan S. Orfali, Al Hassan Gamal El-Din, Varnika Karthik, Elisanjer Lamis, Vanna Xiao, Alena Ramanishka, Abdullah Alwatban, Osama Alkhamees, Ali Alaseem, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate …

Irradiation Of Prostate Cancer Alters Circulating Small Extracellular Vesicle Functions, Aejaz Sayeed, Vaughn Garcia, Cecilia E. Verrillo, Rachel M. Derita, Md Niamat Hossain, Shiv R. Krishn, Samuel Sey, Christopher D. Shields, Adrian D. Altieri, Qin Liu, Khalid Sossey-Alaoui, William K. Kelly, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

It is known that β1 integrins and a downstream signaling molecule c-Src are upregulated in prostate cancer (PrCa) tissues, are co-expressed in circulating small extracellular vesicles (sEVs) and contribute to cancer progression. Here, we demonstrate that sEVs from PrCa patients show robust expression of both β1 integrins and c-Src. The impact of irradiation, a widely used therapy for the treatment of PrCa, on circulating sEVs is however not fully understood. We show that sEVs isolated from the plasma of transgenic adenocarcinoma of mouse prostate (TRAMP) mice, stimulate migration and anchorage-independent growth of recipient cancer cells, but sEVs are not active …

Surface Keratin 1, A Tumor-Selective Peptide Target In Human Triple-Negative Breast Cancer, Shih-Jing Yao, Farideh Amirrad, Elmira Ziaei, Azam Saghaeidehkordi, Moom R. Roosan, Kiumars Shamloo, Ajay Sharma, Rachita K. Sumbria, Surya M. Nauli, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Targeting drugs to cancer cells via overexpressed cell-surface receptors has emerged as an effective therapeutic strategy for several cancers. However, identifying cell-surface receptors that allow selective uptake of targeting ligands by cancer cells—while sparing normal cells—remains a challenge, especially for triple-negative breast cancer (TNBC), which lacks a well-defined receptor for targeted delivery. In this study, immunohistochemical (IHC) analysis revealed that human TNBC patient tissues have significantly higher levels of keratin 1 (K1) compared to normal breast tissues. Among TNBC tissues, grade 3 tumors showed significantly higher (threefold) K1 expression compared to grade 2 tumors. We analyzed human TNBC and normal …

Metabolic And Physiological Regulation In C. Elegans: Insights Into Sperm Activation And Peroxisome-Mediated Longevity, Yash Flora

LSU Doctoral Dissertations

Organelle dynamics lie at the heart of cellular signaling and metabolic regulation, orchestrating physiological processes such as reproduction and aging across the lifespan. In this dissertation, I investigate how organelle-based signaling coordinates sperm activation and modulates organismal aging in the nematode Caenorhabditis elegans. I identify SPIN-4, a previously uncharacterized Spinster family transporter, as a key regulator of spermiogenesis. SPIN-4 is strongly expressed in developing sperm, localizes to the plasma membrane, and promotes sperm activation by facilitating the export of sphingosine-1-phosphate (S1P). Loss of spin-4 results in defective pseudopod formation, reduced motility, and compromised fertility, phenotypes that can be rescued …

An Fgfr-P53 Developmental Signaling Axis Drives Salivary Cancer Progression, Julia M. R. Billington

USF Tampa Graduate Theses and Dissertations

Mucoepidermoid carcinoma (MEC) is the most frequently occurring salivary gland malignancy.Here, we investigated transcriptomic profiles of human fetal and adult salivary glands and MEC tumors to assess programs involved in MEC progression. Molecular and genetic analyses revealed that MEC tumors and fetal salivary glands share proliferative and developmental gene expression profiles that implicate an FGFR-p53 signaling axis in salivary MEC progression. Based on these findings, we developed a genetically engineered mouse model of advanced MEC via targeted expression of the CRTC1-MAML2 oncogene in salivary ductal cells. Specifically, CRTC1- MAML2 expression combined with p53 dysregulation in salivary ducts rewires FGF signaling …

The Only Constant Is Change: The Role Of Genetic Diversification In Cancer And Beyond, Malgorzata Tyczynska Weh

USF Tampa Graduate Theses and Dissertations

Genetic diversification, the process by which genetic variation arises in a population, is fundamental to evolution by natural selection. Mutation, a central diversification process, fuels adaptation across species, including in cancer. Yet most new mutations are neutral or deleterious on cell fitness, raising the question of how mutation-driven adaptation persists. To explore this paradox, I developed a spatial agent-based model (ABM) in which population fitness emerges from individual cells acquiring mutations at varied rates and with diverse fitness effects. I evaluated model behavior across adaptive states, mutation rates, and distributions of fitness effects. The results show that high mutation rates …

Microscopic Nucleic Acid-To-Protein Ratio: A Label-Free Approach For Pancreatic Cancer Detection, Sky Gao, Keerthi Priya Jangili, Alfred Akinlalu, Emmanuel Ogberefor, Tommy Gao, Kalpana Devaraj, Dali Sun

Electrical and Computer Engineering: Faculty Scholarship

Accurate and timely diagnosis remains a major clinical challenge, hindered by the limitations of conventional histopathological methods, which often rely on labor-intensive staining protocols and subjective interpretation by specialized pathologists. These methods can fail to capture the full molecular and phenotypic heterogeneity of tumors, leading to increased diagnostic time, cost, and variability. To overcome these challenges, we developed a novel label-free ultraviolet (UV) microscopic imaging technique that exploits the intrinsic optical absorption properties of cellular nucleic acids and proteins. By modifying standard brightfield microscopes, our approach quantitatively measures the nucleic acid-to-protein ratio (NPr), enabling high-resolution visualization and discrimination between malignant …

Detection Of Quorum-Sensing Molecules In The Mutualistic Bacteria Vibrio Fischeri Exposed To Simulated Microgravity Using Cell-Based Biosensors., Paulina Slick, Maria C. Tobarra, Alba A. Chavez, Hugo Castillo

Beyond: Undergraduate Research Journal

Bacteria flourish in multiple environments when communicating with each other in a process known as Quorum Sensing. This process is accomplished by the production of small signaling molecules referred to as Autoinducers (AI). This communication allows the bacteria to alter their gene expression in an effort to regulate their cell number, behavior, community formation and virulence. The space environment provides stressful conditions for bacteria as they are exposed to radiation and Microgravity (µG or MG) altering synthesis and concentration of Autoinducers. The purpose of this research was to expose the model system Vibrio fischeri to simulated microgravity using the recently …

Exploiting Genomics To Advance Genetic Gain For Reproductive Traits In Sheep, Mujibur Rahman

ORBioM (Open Research BioSciences Meeting)

Poor reproductive performance has a negative impact on the profitability of sheep production systems with the number of lambs reared highlighted as a key driver of farm profitability. Nevertheless, the genetic improvement of reproductive traits in sheep has been constrained by their low heritability and pleiotropic nature. Understanding the underlying genetic architecture can improve genomic prediction estimates and enhance genetic gain.

This study will utilize large-scale genomic and phenotypic datasets to enhance genetic gain in sheep reproductive traits through four approaches: 1) to determine the effect of inbreeding depression on reproduction, 2) to identify causal variants impacting reproductive performance through …

Is Anoxia Tolerance A Common Trait In Fish Cell Lines?, Lori Tran

University Honors Theses

Most vertebrates need a constant supply of oxygen to sustain life, with disruption to O₂ supply or delivery quickly leading to cell and tissue damage and death. Many aquatic species are able to withstand long periods without O₂ due to evolving to survive the regular periods of hypoxia and anoxia in their natural habitat. The Austrofundulus limnaeus, or the annual killifish, in particular have shown the highest anoxia tolerance in all vertebrates and is a promising model for developing effective treatments for anoxia-related damage, such as heart attacks and strokes. The A. limnaeus are not the only …

Murine Tbk1 Regulates Mpp3-Type Hspcs And Circulating Leukocytes In Normal Hematopoiesis And Flt3+ Lscs In Mll-Af9-Driven Leukemia, Austin P. Runde, Joseph Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Rohit Thalla, Allan Youmaran, Mattias Lenz, Peter Breslin, Wei Wei, Jiwang Zhang

School of Medicine

BACKGROUND: Acute myeloid leukemia (AML) is an aggressive hematologic cancer with a notoriously bleak prognosis; for non-M3 AML, the overall 5-year survival rate is ∼30%. While 60-70% of newly diagnosed AML patients will achieve complete remission (CR), half of these patients will experience relapse (secondary resistance) by three years from their diagnosis. Moreover, 30-40% of AML patients present with refractory disease (primary resistance) and cannot respond to frontline treatments. Leukemia stem cells (LSCs) are implicated in both primary and secondary resistance, and their eradication is necessary to maintain CR. LSCs have unique transcriptomes and immunophenotypes, thus can be identified relatively …

Carbon Monoxide Releasing Polymeric Micelles, Riya Joshi

Electronic Theses and Dissertations

Carbon monoxide (CO), traditionally known as a toxic gas, has emerged as a potential therapeutic agent due to its cytoprotective, anti-inflammatory, and vasodilatory properties. This study explores the development of CO-releasing polymeric micelles as a controlled delivery system for biomedical applications. Using ring-opening metathesis polymerization (ROMP), we synthesized diblock copolymers incorporating CO-releasing moiety diphenylcyclopropenone (DPCP) with hydrophilic polyethylene glycol (PEG) to enhance solubility and stability of the overall CO releasing system. Dynamic light scattering (DLS) and electron microscopy (EM) confirmed the formation of well-defined micelles, while fluorescence assays demonstrated efficient CO release with the use of Iridium photocatalyst under 470 …

Abstract 2853 Prmt7 Negatively Regulates The Expression P53 In Response To Dna Damage, Molly Niswender, Lorenzo Pessi, Cecilia Lopez, Marco Bisoffi

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Protein Arginine Methyltransferase 7 (PRMT7) is the only member of the protein arginine methyltransferase protein family that monomethylates its protein substrates. PRMT7 is found in both the nucleus and cytoplasm of breast cells and is believed to play a robust role in the tumorigenesis and metastasis of breast cancer. The goal of this project is to uncover possible pathways for PRMT7 to promote cancer progression. A preliminary antibody array was performed to determine the regulation of known cancer-related proteins by PRMT7. An early-stage human breast cancer cell line, MCF-7, was transfected with plasmid pCDH1-hPRMT7-GFP to over-express PRMT7. Qualitative and quantitative …

The Anticancer Activity Of Novel Chromene Derivatives Against Colorectal Cancer Cells, Rym Magramane

Thesis/ Dissertation Defenses

Colorectal cancer (CRC) stands as the third most common cancer globally, accounting for nearly 10% of all newly diagnosed cancer cases. In the UAE, CRC was ranked as the third most frequently diagnosed malignancy, and the leading cause of cancer-associated deaths in 2023. Standard CRC treatment strategies include surgical resection, chemotherapy, immunotherapy, targeted therapy, or a combination of all, depending on the cancer stage and molecular profile. Despite these interventions, disease recurrence is experienced by a considerable number of cancer patients. Hence, there is an urgent need to develop novel alternative treatments to overcome poor prognosis. Recently, cancer research has …

Ensemble-Based Binding Free Energy Profiling And Network Analysis Of The Kras Interactions With Darpin Proteins Targeting Distinct Binding Sites: Revealing Molecular Determinants And Universal Architecture Of Regulatory Hotspots And Allosteric Binding, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

KRAS is a pivotal oncoprotein that regulates cell proliferation and survival through interactions with downstream effectors such as RAF1. Despite significant advances in understanding KRAS biology, the structural and dynamic mechanisms of KRAS allostery remain poorly understood. In this study, we employ microsecond molecular dynamics simulations, mutational scanning, and binding free energy calculations together with dynamic network modeling to dissect how engineered DARPin proteins K27, K55, K13, and K19 engage KRAS through diverse molecular mechanisms ranging from effector mimicry to conformational restriction and allosteric modulation. Mutational scanning across all four DARPin systems identifies a core set of evolutionarily constrained residues …

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 …

Topodino: Self-Supervised Topological Representation Learning For Neuronal Morphologies, Yasser Binbisher

Master's Theses

Neuronal cell types are categorized by transcriptomic identity, yet their morphological heterogeneity defies this classification. In response, researchers have adopted unsupervised graph representation learning as a tool to reveal morphological variation within single-class transcriptomic types. However, the complex geometry of neuronal morphology—especially long axons and dense dendrites—challenges graph neural networks, which struggle with message propagation across extended structures. To mitigate this, current approaches enforce sub-sampling on neuronal graphs and omit axons entirely, sacrificing critical biological features for computational efficiency. To overcome this trade-off, this thesis introduces TopoDINO, a self-supervised, topology-aware representation learning model designed to preserve the full hierarchical organization …

Investigating A Link Between Dna Repair And Dna Replication In Escherichia Coli Using A Bacterial Two-Hybrid System, Lo Cooper

University Honors Theses

Cells rely on nucleotide excision repair (NER) to remove bulky DNA lesions, such as those caused by UV light. In Escherichia coli, NER involves the UvrABC complex, and includes two main pathways, global genomic repair and transcription-coupled repair (TCR). While TCR, which preferentially removes lesions that block RNA polymerase on the transcribed strand of active genes, is well studied, less is known about whether a similar coupling between repair proteins and replisomes blocked by damaged DNA exists. Such a process has been suggested by a high throughput interactome study, using the replisome subunit HolC as bait and the damage …

Basal Autophagy Promotes Accurate Chromosome Segregation In Drosophila Oocytes And Declines During Oocyte Aging, Diana C. Hilpert

Dartmouth College Ph.D Dissertations

The frequency of trisomic pregnancies exponentially increases with advanced maternal age, a phenomenon known as the maternal age effect. The majority of these aneuploid pregnancies arise from meiotic segregation errors in the oocyte and premature loss of sister chromatid cohesion is a contributing factor. However, the mechanisms that lead to premature cohesion loss during oocyte aging are not fully understood.

Using Drosophila melanogaster as a model organism, work described in this dissertation demonstrates that basal levels of autophagy, a degradation process for damaged organelles and protein aggregates, are required during meiotic prophase for arm cohesion maintenance and accurate meiotic segregation …

Elucidating The Roles Of Eukaryotic Initiation Factors Involved In Dap5 Mediated Translation, Jacob Nk Quartey

Dissertations, Theses, and Capstone Projects

Translation initiation in eukaryotes is a highly regulated process essential for accurate protein synthesis. It is a dynamic process that involves a complex interplay between messenger RNAs (mRNAs), ribosomal subunits, and a host of initiation factors, ensuring precise start codon selection and the subsequent assembly of the translation machinery. This process has well been known to be mediated by the eukaryotic Initiation Factor (eIF4F), which consists of the cap binding protein eIF4E, the scaffolding protein eIF4GI, and the helicase factor eIF4A.The recognition and binding of eIF4E to the m⁷G cap structure of the mRNA is essential for the …