Cell and Developmental Biology Commons^™

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 …

Profiling Nucleolin Phosphorylation During Dna Damage Response And Cell Cycle Arrest, Hanjun Jeon

Dissertations, Theses, and Capstone Projects

This dissertation examines site-specific and global phosphorylation dynamics of nucleolin (NCL) in response to DNA damage and cell-cycle perturbations. By combining phospho-specific immunoblotting with Phos-tag SDS-PAGE analysis, distinct phosphorylation patterns were identified across experimental conditions. The results define reproducible, condition-dependent phosphorylation states of NCL and provide a framework for studying its regulation under cellular stress.

The Effects Of Cinnamaldehyde On Tetrahymena Thermophila, Sydney Kurland

Publications and Research

In addition to their common use as spices in cooking and baking, cinnamon plants, Cinnamomum zeylanicum and Cinnamomum cassia for example, have long been used in herbal remedies worldwide. Cinnamon contains many vital oils and active compounds including cinnamaldehyde (CMD). Numerous studies looking at potential therapeutic effects of cinnamon have demonstrated its antioxidant, anti-inflammatory, and antimicrobial properties (1, 2, 3).   Therefore, it is important to continue studying the efficacy, benefits, and mechanisms of action of cinnamon and CMD to have a complete understanding of its full potential. Tetrahymena thermophila is a ciliated protozoan commonly used as a model organism to …

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 …

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 …

Characterization And Advancement Of Molluscan Venom Gland Cell Model Systems, James V. Parziale

Dissertations, Theses, and Capstone Projects

Venomous mollusks, including cone snails and coleoid cephalopods, produce rich repertoires of bioactive peptides with profound effects on cellular physiology, yet there are few tractable experimental systems that exist to study their development, maintenance, and venom secretion. Although therapeutics such as the cone snail peptide Ziconotide demonstrate the biomedical potential of molluscan venoms, progress in understanding how venom glands form, function, and evolve has been hindered by the lack of reliable husbandry and the complete absence of in vitro cell models. Modern comparative genomics has revealed widespread convergent evolution across venomous lineages, but molluscan datasets remain underrepresented, limiting insights into …

Potential Role Of A Ruthenium-Based Compound Ru-Im In The Treatment Of Triple Negative Breast Cancer, Rachele Rameau

Dissertations, Theses, and Capstone Projects

Triple negative breast cancer (TNBC) is an aggressive and heterogeneous molecular subtype of breast cancer that has limited available treatments. The organometallic cationic ruthenium derivative Ru-IM was found to be highly water soluble, was differentially toxic for breast cancer cells and tumors, and was involved in the pI3K/AKT/mTOR pathway. However, a full understanding of genetic and epigenetic factors that can be part of regulatory mechanisms of Ru-IM is yet to be determined. Epigenetic assays including DNA methylation, histone acetylation and histone deacetylation were performed with the half inhibitory concentration (IC50) values of Ru-IM. Bisulfite sequencing of untreated and treated MDA-MB-231 …

Retinal Precursor Cell Enriched Multiomic And Pseudo-Time Analysis Of Developing And Reprogrammed Photoreceptors, Brendon M. Patierno

Dissertations, Theses, and Capstone Projects

The vertebrate retina is a complex tissue made up of seven major cell subtypes which during development must differentiate and localize into a highly organized structure. These neuronal cells do not regenerate if damaged or diseased, and the progressive deterioration of cone photoreceptor cells is the leading cause of age related blindness. Currently there are no cures for this disease, but one promising therapeutic avenue is cell transplantation research. If we can further elucidate the gene regulatory networks that define cone cell development, this knowledge could be applied to the generation of healthy cone cells in clinically relevant models.

The …

The Sonic Hedgehog Effector Smoothened Modulates Cholinergic Interneuron Activity, Physiology, And Striatum-Dependent Behaviors, Santiago Uribe-Cano

Dissertations, Theses, and Capstone Projects

The striatum is a central node in action selection and associative learning, integrating cortical, thalamic, and neuromodulatory input. Among its principal modulators, dopamine (DA) and acetylcholine (ACh) are known for their temporally coordinated yet mechanistically distinct influences on striatal output. However, the upstream signals that regulate their dynamic interplay, particularly within cholinergic interneurons (CINs)—the primary source of striatal ACh—remain incompletely characterized. This dissertation investigates the role of Smoothened (Smo), a G protein-coupled receptor (GPCR) effector of Sonic Hedgehog (Shh) signaling, in modulating ACh signaling dynamics in the striatum.

Building on evidence that midbrain DA neurons co-release Shh and that CINs …

Mechanistic Insights Into The Neuroprotective Effects Of The Antidepressant Agomelatine In Alzheimer's Disease, Grace Terry

Dissertations, Theses, and Capstone Projects

Alzheimer’s Disease (AD) is a complex neurodegenerative disease that has limited treatment options and no cure. AD is characterized by robust pathology including extracellular amyloid beta plaques, intracellular neurofibrillary tangles, neuronal and synaptic loss, neuroinflammation, and brain atrophy. AD presents with cognitive decline and memory loss but only years after neuropathology has started to accumulate. This robust pathology has made AD difficult to treat and highlights the need for therapeutics that modulate multiple pathways. Agomelatine (AGO) was selected by a high-throughput machine learning drug repurposing algorithm by our collaborator Dr. Lie Xie (Hunter College Dept. of Comp. Sci.) as having …

Bmp Signaling Co-Regulation Of Immune Response And Lipid Metabolism, Katerina K. Yamamoto

Dissertations, Theses, and Capstone Projects

The Bone Morphogenetic Proteins (BMPs) are secreted peptide ligands of the Transforming Growth Factor beta (TGF-β) family, initially identified for their roles in development and differentiation across animal species. They are now increasingly recognized for their roles in physiology and infectious disease. In the nematode Caenorhabditis elegans, the BMP ligand DBL-1 controls fat metabolism and immune response, in addition to its roles in body size regulation and development. DBL-1 regulates classical aspects of innate immunity, including the induction of anti-microbial peptides. We theorized that BMP-dependent regulation of fat metabolism could also promote resilience against microbial pathogens. We found that …

Investigating The Role Of Early Growth Response 1 (Egr1) Gene In Riluzole-Induced Apoptosis In Osteosarcoma, Syeda Maryam Azeem

Dissertations, Theses, and Capstone Projects

Osteosarcoma is a rare but aggressive bone malignancy most commonly affecting adolescents and young adults (AYA). With 5-year survival rate stagnating over the last four decades despite the advancements in multi-modal therapy, drug repurposing offers a rapid path to new osteosarcoma treatments. Recent studies suggest that Riluzole, a drug approved for amyotrophic lateral sclerosis (ALS), may be repurposed for osteosarcoma treatment due to its ability to slow tumor progression and induce apoptosis. Previously, we have shown that Riluzole increases reactive oxygen species (ROS), activating c-Abl, which phosphorylates YAP in the nucleus. YAP then forms a complex with p73 to enhance …

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 …

Understanding How Genetic Mutations Induce Oligodendrocyte Progenitors To Become Cancer Cells, Dennis Huang

Dissertations, Theses, and Capstone Projects

Gliomas are the most devastating adult brain tumors characterized by poor survival rate and limited options for treatment. Previous studies have shown that they are very heterogeneous and can be further sub-classified based on their transcriptional signature and the presence of specific mutations. One such subtype, is the “proneural glioma”, which is characterized by the enrichment in oligodendrocyte progenitor cell (OPC) transcripts and mutations in genes encoding for the tumor suppressor P53 (Trp53) and for Platelet Derived Grow Factor (PDGF) signaling. Since OPCs are the most abundant proliferative population in the adult brain, in this …

Unpaired Virtual Histological Staining Of Tissue From Autofluorescence Using Regularized Cycle-Consistent Adversarial Networks, Zhesi Wen

Theses and Dissertations

We present a regularized CycleGAN with a Dense Residual U-Net to virtually stain autofluorescence images of tissue into H&E-like images. Our method outperforms standard architectures, reduces artifacts, and achieves superior FID scores, enabling efficient, label-free, and accurate digital pathology for unpaired datasets using multi-channel fluorescence inputs.

The Role Of Elongin B In Drosophila Melanogaster Muscle Development, Madelyne Dayan

Student Theses and Dissertations

Muscle atrophy is a result of a number of muscle diseases, as well as aging, disuse, and infections. Muscles weakened in these ways exhibit a characteristic decrease in size, strength, and mobility. The similarities between muscle in humans and Drosophila allow for direct comparisons to be made in vertebrates from studying muscle in Drosophila. Differential gene expression has been shown to play an important role in embryonic muscle development in Drosophila melanogaster. A previous study identified Elongin B (EloB) to be involved in somatic muscle morphogenesis in Drosophila, with mutant embryos displaying severe muscle defects, including thin, mis-attached, and missing …

Investigating Genetic Regulators Of Crystal Cell Development In Drosophila Melanogaster, Andrea Feria, Nyla Walbrook, Anisa Turaeva, Rebecca Spokony

Publications and Research

Crystal cells, a subset of Drosophila melanogaster hemocytes, are important for melanization, a crucial immune response. While the genetic regulation of crystal cell develop remains incompletely understood, this study investigates the functions of five candidate genes: ACXB, ACXA, Gp210, CG4390, and Cyp4s3; identidied through previous genome-wide association studies. Using the Gal4/UAS system along with RNA interference (RNAi), we exclusively knocked down each gene in third instar larvae and quantified crystal cell populations following heat shock-induced melanization. Our results imply that the knockdown of ACXB and ACXA significantly increased crystal cell counts in both sexes, suggesting these genes either act as …

The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker

Dissertations, Theses, and Capstone Projects

Under normoxic conditions, eukaryotes initiate translation of RNA through eIF4E recognition of the 5’ cap. However, under cellular stress, eukaryotic translation must be initiated through a 4E-independent, or “cap-independent” mechanism, involving eukaryotic initiation factor 4G (eIF4G) binding directly to the 5’ untranslated regions (5’ UTR) of the RNA. eIF4G binding then recruits the ribosome to the transcript. While this mechanism is useful for translation of apoptotic transcripts and transcripts involved in cell survival, cap-independent translation is also utilized by oncogenic RNA for tumorigenesis. Previous work by our lab and others has categorized this recruitment and initiation mechanism as either internal-ribosome-entry-site …

Atorvastatin Alters Neuronal Morphology Data Set, Carolyn L. Pytte

Publications and Research

Statins are highly effective and widely prescribed cholesterol lowering drugs. However, statins cross the blood-brain barrier and decrease neural cholesterol in animal models, raising concern that long-term statin use may impact cholesterol-dependent structures and functions in the brain. Cholesterol is a fundamental component of cell membranes and experimentally decreasing membrane cholesterol has been shown to alter cell morphology in vitro. In addition, brain regions that undergo adult neurogenesis rely on local brain cholesterol for the manufacture of new neuronal membranes. Thus neurogenesis may be particularly vulnerable to long-term statin use. Here we asked whether oral statin treatment impacts neurogenesis …

Caspases Protect Against Hyperglycemia Induced Necroptosis-Like Cell Death In Brain Endothelial Cells, Aleena S. Mathew

Theses and Dissertations

Acute diabetes characterized by high spikes in blood glucose levels in association with severe hyperglycemia can lead to an increased risk of ischemic stroke in the brain. To better understand high blood glucose levels, hyperglycemia, in the brain we explored its effects on endothelial cells. Endothelial cells line the inner walls of blood vessels and are directly impacted in hyperglycemia. Brain endothelial cells are a major component of the blood brain barrier (BBB) which tightly regulates the brain’s microenvironment. The type of cell death such as apoptosis, caspase dependent, or necroptosis, caspase independent, can exacerbate diabetes associated complications. There is …

Autophagy And Meiotic Fidelity In C. Elegans, Kaitlin E. Kosinski

Dissertations, Theses, and Capstone Projects

Autophagy is an evolutionarily conserved multi-step recycling process in which cellular material is enclosed in the double membrane-bound autophagosome, which fuses with the lysosome to degrade its contents. Autophagy is essential for development and cellular adaptation to environmental or intracellular stress and is an important regulator of germline stem cell homeostasis in the model nematode C. elegans. We sought to determine if autophagy is important for genome stability during meiosis and found that the core adult C. elegans autophagy genes bec-1, atg-7, unc-51, and atg-18 were all required for proper meiotic development of oocytes. Loss of these …

Assessment Of Tripeptides Self-Assembly & Er Stress On Cell Viability And Exosome Secretion In Mda-Mb231, Azmat Parveen

Theses and Dissertations

This study delves into the effects of tripeptides KYpF and WYpK(NBD) on MDA-MB-231 cells, uncovering KYpF's ability to reduce cell proliferation and exosome secretion in peptide treated cells. Conversely, WYpK(NBD) demonstrated significant toxicity at 10 μM. These insights pave the way for optimizing peptide-based cellular treatments for exosome secretion purposes.

Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane

Theses and Dissertations

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. IL-24 induces cancer-specific apoptosis by activating endoplasmic reticulum (ER) stress and mitochondria dysfunction. We have previously demonstrated that IL-24 leads to apoptosis in cancer cells by protein kinase A (PKA) activation in human breast cancer cells. To further understand the mechanism by which IL-24 induces apoptosis, I analyzed the role of glycogen synthase kinase-3 (GSK3), a highly conserved and normally active serine/threonine kinase in cancer cells and downstream target of PKA. The work reported here provides direct evidence that GSK3 was inhibited following IL-24 treatment in human prostate cancer …

High Mdmx (Mdm4) In Mutant P53 Expressing Breast Cancer Cells Activates The Cxcl12-Cxcr4 Metastasis Signaling Axis, Rusia H. Lee

Dissertations, Theses, and Capstone Projects

The metastasis-promoting G-protein coupled receptor (GPCR) CXCR4 is activated by the cytokine CXCL12 (also known as SDF-1) to promote metastasis through CXCR4 upregulation. High CXCR4-expressing cancer cells utilize CXCL12, the exclusive endogenous ligand of CXCR4, to intravasate into the blood as circulating tumor cells (CTCs) which then extravasate to distant metastatic sites. We previously determined the oncogenes, Mouse Double Minute 2 and 4 (MDM2 and MDM4, also known as MDMX), drive TNBC metastasis and positively correlate with high expression of CXCR4. Interestingly, this upregulation of CXCR4 was only observed in primary tumor cells grown in the tumor microenvironment …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Stability Of Dna In Saliva Evidence Collected With Two Different Swabbing Solutions, Kuanwei Lu

Student Theses

As the significance of trace DNA has increased over time, it has become more important to optimize each process to avoid any loss of genetic material. Factors that could negatively affect the quality and quantity of DNA during transport or storage include environmental temperature, the DNA collection devices, the packaging, and possible contamination. This study compared the DNA stability of saliva stain swabs collected by moistening the swab with deionized water or Sample Keeper and stored at room temperature. Sample Keeper (Microread Genetics, Beijing) is a proprietary buffer marketed as a DNA stabilizing agent. We swabbed 110 saliva stains from …

Mechanistic And Engineering Studies Of Lov Photoreceptors In Yeast, Matthew M. Cleere

Dissertations, Theses, and Capstone Projects

A variety of cellular biosensors have evolved which can translate electromagnetic radiation from the environment into biological functions. Light-Oxygen-Voltage (LOV) domains in particular, are a group of photoreceptors that respond to blue wavelengths of light and can become a cellular photoswitch by converting this stimulus through their attached effector domains. For instance, the Helix-Turn-Helix (HTH) DNA-binding activity of the bacterial transcription factor EL222 and the Regulator of G-protein Signaling (RGS) in the fungal membrane associating protein BcLOV4 are both induced by blue-light sensing LOV domains. While previous work has provided the field with a structural characterization of LOV proteins in …

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …