Cell and Developmental Biology Commons^™

Investigating The Antibacterial And Immunomodulatory Effects Of Resolvin D2 On Monocytes And Macrophages, Cristina Maria Padovani

Theses and Dissertations

In the late phase of sepsis, immunosuppression occurs, where the host is unable to clear the pre-existing infection and is susceptible to secondary infections. It is believed that the ideal treatments for sepsis should attenuate immunosuppression so that the host can get back to homeostasis. Specialized Pro-resolving Mediators (SPMs) are endogenously- produced fatty acids that resolve infectious inflammation without being immunosuppressive. We hypothesize that an SPM – Resolvin D2 (RvD2) – can augment exhausted macrophage function during the immunosuppressive phase of sepsis. We developed a two-hit model to establish macrophage exhaustion in vitro, and found that RvD2 increased NF-κB activity, …

Regulation Of Intracellular Sorting Of The Bruno Protein In Drosophila Flight Muscles, Travis Main

Master's Theses

Understanding mechanisms of intracellular sorting is a fundamental inquiry of cell biology. We used the B-body and protein Bruno (Bru) as a model to study the formation of nuclear domains that are membraneless organelles inside the cell nucleus. Specifically, we sought to identify protein sequences that regulate Bru's affinity to B-bodies and protein aggregation. We generated various Bru mutants and subsequently tested them in vivo using fluorescence microscopy. We found that the protein solubility of Bru is determined through an interplay of RNA recognition motifs (RRMs) and intrinsically disordered regions (IDRs). Using truncation analysis, we identified a 31-amino acid region …

Neuroinflammation Levels Measured By Microglial Cell Activation, Emma G. Whitlock, Linda S. Yasui

Honors Capstones

Neuroinflammation is an inflammatory response in the brain that can be caused by different stressors such as diseases and/or external factors such as traumatic brain injuries. It is important to note duration and intensity of neuroinflammation levels when determining the impacts of these stressors to the brain environment. During neuroinflammation, a type of immune cell that becomes activated in the brain is called microglial cells. Microglial cells play a role in progression of the pathophysiological effects from the brain stressor. Studying changes in microglial cell shape provides evidence of the degree of neuroinflammation in the brain. Researchers can quantify neuroinflammation …

Mucins: Drivers Of Cancer Cell And Microenvironment Crosstalk In Pancreatic Cancer, Xiaoqi Li

Theses & Dissertations

Mucins facilitate the pancreatic cancer (PC) initiation, progression, and metastasis. Among mucins, MUC4 has been reported to inhibit lymphokine-activated cell killing and induce the apoptosis of cytotoxic T-cells. Counterintuitively, MUC4 expression is upregulated by multiple T-cell-secreted cytokines, such as IFN-γ, IL-17, and stroma-secreted factors like retinoic acid. Previously, we have identified that nuclear receptor coactivator 3 (NCOA3) regulates the MUC1 and MUC4 expression by increasing chromatin accessibility and maintaining protein stability. However, the comprehensive crosstalk mediated by MUC4 in cancer cells and T-cells and how its upstream regulator, NCOA3, modifies the cancer cell-intrinsic behavior is still elusive. Here, we show …

Targeting Lifr/C-Myc/Ddx21 Axis To Overcome Docetaxel Resistance In Prostate Cancer, Sushanta Halder

Theses & Dissertations

Resistance to chemotherapy poses a significant challenge in the treatment of advanced-stage prostate cancer (PCa), specifically with chemotherapy drugs like docetaxel (Doce), which is often employed after the failure of hormone therapy. However, 50-90% of PCa patients develop resistance to docetaxel within three years of post-chemo treatment, compounded by serious adverse side effects necessitating dose reductions. Various strategies are being investigated to address this issue, including identifying new therapeutic targets or mechanisms, developing novel combination therapies, and optimizing dosing regimens. In particular, our research is focused on uncovering the underlying mechanisms of resistance to docetaxel, such as the activation of …

Identification Of Mitotic Phosphatases And Cyclin K As Novel Molecular Targets In Pancreatic Cancer, Yi Xiao

Theses & Dissertations

Pancreatic cancer is a highly lethal disease worldwide. Given the limited effectiveness of current regimens in restricting tumor progression, it is imperative that potential molecular targets be identified to offer valuable insights into alternative therapeutics. By using a phosphate-binding tag (Phos-tag) technique, previous studies have identified several Hippo pathway-related proteins and kinases required for cancer growth or paclitaxel resistance. This work has screened various phosphatases and cyclins/cyclin-dependent kinases (CDKs) as potential cancer targets, but specifically focuses on characterizing the roles of carboxy-terminal domain small phosphatase like 2 (CTDSPL2), apoptosis-stimulating protein of p53-2 (ASPP2), and Cyclin K in pancreatic cancer.

CTDSPL2 …

Identifying The Molecular Determinants Of Lung Metastatic Adaptation In Prostate Cancer, Grace M. Waldron

Theses & Dissertations

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou

Theses & Dissertations

Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …

Homeobox A10: Regulator Of Pancreatic Cancer Progression And Survival, Sophia G. Kisling

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest incidence rates among all major cancers, yet it is disproportionally responsible for 8% of all cancer deaths. This high death rate is primarily attributed to the immunosuppressive tumor microenvironment and a lack of clinically relevant molecular targets. However, the underlying biology responsible for these poor outcomes remains obscure. To facilitate improved management of PDAC, an in-depth understanding of the molecular player(s) involved in PDAC aggressiveness is needed. Therefore, we analyzed the transcriptomic profiles of PDAC patients with long- and short-term survival and performed gene set enrichment analysis (GSEA), identifying a novel …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Understanding The Non-Canonical Regulation Of Srebp In Aspergillus Fumigatus, Muhammad Abubakar Khan

Dartmouth College Ph.D Dissertations

Aspergillus fumigatus is an opportunistic fungal pathogen causing invasive pulmonary aspergillosis (IPA), with high mortality rates in immunocompromised individuals. Adaptation to the hypoxic microenvironment of IPA is crucial for fungal virulence. The transcription factor SrbA, a Sterol Regulatory Element-Binding Protein (SREBP) homolog, plays a key role in this hypoxic response and regulates genes involved in hypoxic growth, sterol biosynthesis, and azole resistance, making it an attractive therapeutic target.

However, SrbA activation in A. fumigatus lacks critical components of the canonical SREBP pathway, such as SCAP, Site-1 protease (S1P), and Site-2 protease (S2P). Instead, the rhomboid protease RbdB, signal peptide peptidase …

Efficacy Of Mcl-1 Inhibitors In Multiple Myeloma Cells Resistant To Bortezomib, Emily Nelson, Omar S. Al-Odat, Sabrina M. Paparo, Daniel A. Guirguis, Gabriella Yao, Manoj Pandey, Subash Jonnalagadda, Tulin Budak-Alpdogan

Rowan-Virtua Research Day

Multiple myeloma (MM) is a type of cancer that affects plasma B cells. Patients with MM often experience frequent relapses and can develop resistance to drugs. As a medical researcher, it is important to understand the role of Mcl-1 in preventing intrinsic apoptosis and drug resistance. Mcl-1 belongs to the anti-apoptotic subgroup of Bcl-2 family proteins and plays a crucial role in these processes. Mcl-1 plays a crucial role in driving disease progression and contributing to drug resistance in MM. It has been observed that there is an increased expression of Mcl-1 in 52% of patients with MM during diagnosis, …

Investigating The Therapeutic Potential Of Soursop In Treating Hematologic Malignancies, Sabrina Marie Paparo, Rebeca Mendoza, Robert Chitren, Omar Al-Odat, Emily Nelson, Subash Jonnalagadda, Roger Strair, Manoj Pandey

Rowan-Virtua Research Day

Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) are hematologic malignancies that originate in the bone marrow and account for approximately 1.3% and 2% of cancer cases, respectively. AML is characterized by an accumulation of myeloblasts, or immature myeloid cells, that have the potential to spread to the peripheral blood. There is an uncontrolled proliferation of plasma cells in the bone marrow in MM. While the current treatment options for both AML and MM show promise in achieving initial remission, it is unfortunately common for patients to experience relapse and develop drug resistance. There is a theory that relapse and …

Microglial Dynamics And Mechanisms Underlying The Phagocytosis Of Dying Oligodendrocytes, Genaro E. Olveda

Dartmouth College Ph.D Dissertations

Myelin is a complex multilamellar structure, generated by oligodendrocytes, that ensheaths axons and is a vital component for neural processing. Degeneration of both oligodendrocytes and their myelin sheaths is a common pathological feature associated with aging and neurodegenerative diseases. Efficient removal of the cellular and myelin debris is crucial for remyelination and prevention of further degeneration. Microglia, the primary phagocytes of the CNS, are thought to play a key role in this process. To investigate the cellular dynamics underlying microglia-mediated clearance of degenerating oligodendrocytes and myelin sheaths, at the single cell level, we developed a novel model for inducible cortical …

Intra-Accumbens Microinfusion Of The Dopamine D3 Receptor Partial Agonist (±)Vk4-40 Does Not Affect Basal Locomotion In Mice, Yeonwoo Sim, Nicole M. Hinds, Amy Hauck Newman, Daniel F. Manvich

Rowan-Virtua Research Day

The opioid epidemic remains a pressing public health crisis, prompting the search for alternative pharmacotherapies for Opioid Use Disorder (OUD). This study explores the potential of the dopamine D3 receptor (D3R) partial agonist, (±)VK4-40, as a novel treatment option. We investigated the impact of intra-nucleus accumbens (NAc) microinfusion of VK4-40 on basal locomotion in mice. Results indicate that VK4-40 did not significantly alter basal locomotion, suggesting that its therapeutic effects may not be mediated through disruptions in generalized motor function. Future research will focus on elucidating the neuropharmacological mechanisms underlying VK4-40's therapeutic actions and exploring its effects on psychostimulant-induced hyperlocomotion. …

Fiddler Crab Gut Microbiomes As An Indicator For Eutrophication Due To Waste-Water Contamination In Estuaries, Madison L. Geraci

Honors Theses

Estuaries are unique biogeochemical zones in coastal systems that provide a myriad of ecological functions: providing habitat for critically important fishery species, diverse species of plants and animals, and contributing to nutrient cycling. Estuaries are vulnerable to anthropogenic stressors as they are intersections between marine and terrestrial communities and are often the hotspot of coastal development and activity. Estuarine sediments act as repositories for anthropogenic contaminants, including excess nutrient runoffs and waste-water pollution that can cause states of eutrophication. Microorganisms are sensitive to these environmental changes, presenting a unique opportunity of being useful bioindicators of environmental stress. Isolating microorganisms from …

The Effect Of Diabetes Mellitus On Differentiation Of Mesenchymal Stem Cells Into Insulin-Producing Cells, Mohamed M. Kamal, Omar I. Badr, Shohda A. El-Maraghy, Heba R. Ghaiad

Pharmacy

Background

Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro.

Methods

We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and …

Uncovering Novel Small Regulatory Rna In Protostome, Sweta Khanal

Dissertations

Small RNAs play pivotal roles in post-transcriptional gene regulation across diverse phylum of protostomes. In this study, we investigate the functional significance of atypical miRNAs, mirtron miR-1017 in Drosophila. Through ectopic expression in neuronal cells, we demonstrate that miR-1017 extends lifespan by targeting its host transcript, acetylcholine receptor Dα2, and influencing its splicing. This novel trans-regulatory function suggests a mechanism for mirtron evolution, highlighting the interplay between splicing and post-transcriptional regulation. Additionally, we profile small RNA populations in the polychaete developmental model Capitella teleta, shedding light on the small RNA landscape in annelid worms. Our analysis reveals a rich …

Identifying The Roles Of Mir-17 In Ciliogenesis And Cell Cycle, Ashwaq Alanazi

Pharmaceutical Sciences (PhD) Dissertations

Emerging evidence suggests a significant contribution of primary cilia to cell division and proliferation mechanisms. MicroRNAs, especially miR-17, contribute to cell cycle regulation and proliferation. Recent investigations have highlighted the dysregulated expression of miR-17 in various malignancies, underlining its potential role in cancer. However, the correlation between primary cilia and miR-17 has yet to be fully elucidated. The present study examines the presence of miR-17 in primary cilia. The miR-17 expression is studied in selected ciliary protein knockdown cells. Using in-situ hybridization (ISH), we identified the subcellular localization of miR-17 in both cilia and cell bodies. We confirmed the importance …