Cell and Developmental Biology Commons^™

A Genomics Driven Induced Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia - Early Results, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Research Days

While the cure rates for pediatric ALL have improved over the decades, infants with ALL (iALL) have not benefitted from these advances and continue to have a devastating prognosis. Unfortunately progress in treatment has also been slowed by inadequate research models. With this project, we address this unmet need by investigating a novel model to understand the cellular and molecular changes that occur during iALL onset and progression.

Statistical Mobility Of Aggregated Microswimmers, Yonatan Ashenafi

Biology and Medicine Through Mathematics Conference

No abstract provided.

Optimizing Immunotherapies For Improved Cancer Treatment, Anne Talkington, Anthony Kearsley

Biology and Medicine Through Mathematics Conference

No abstract provided.

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Cell Cycle Regulator Delays Pilus Production In Caulobacter Crescentus, Eli Johnson

Honors Theses

Caulobacter crescentus is a model bacterium for its unusual life cycle. This cycle features three distinct phases- the stalked stage, pre-divisional or actively dividing stage, and the swarmer stage, characterized by the production of a flagellum and multiple pili. Pili are necessary for cell attachment to surfaces and their reuptake into the cell can help drive the cell cycle forward. The gene that encodes the pilus subunit, pilA, is regulated by four binding sites for the cell cycle regulator CtrA. Previous research has determined that one site induces expression while two of the four sites inhibit expression. It is unknown …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Identifying Novel Upstream Regulators Of The Hippo Pathway: Forward Genetic Screen In Drosophila Melanogaster, Akshara Iyer

Honors Scholar Theses

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range of human disorders, including cancer. The physiological function of the Hippo pathway is best understood in Drosophila, where inactivation of the Hippo pathway tumor suppressors, or overexpression of the Yorkie (Yki) oncoprotein, results in tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis, and increased transcription of Hippo pathway target genes such as diap1 and expanded (ex). Despite the well-established Hippo pathway core signaling cascade, the upstream regulation of …

Characterizing The Expression Of The Sphingosine 1-Phosphate Pathway In Injury And Post-Traumatic Fibrosis, Nicole Cubbage

Masters Theses, 2020-current

Following injury, tissue repair allows for the restoration of the architecture and function of the injured tissue, while tissue replacement is characterized by severely damaged or non-regenerable tissue that is repaired by the laying down of extensive connective tissue, also known as fibrosis. The fibrotic process should be arrested at its early stage to have the greatest impact on preventing or reversing associate sequelae and promoting the regeneration of normal tissue. Sphingosine 1-phosphate (S1P), a metabolic product of cell membrane sphingolipids, has emerged as a pathway that may be involved in fibrosis. Most of S1P’s actions are mediated through the …

Examining The Role Of Rgs2 In The Maintenance Of Diapause After Anoxic Stress In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Patrick Clouser

Student Research Symposium

Austrofundulus limnaeus live in ephemeral ponds of Venezuela. They have evolved a unique life history that includes embryonic diapause, a period of developmental dormancy, metabolic arrest, and reduced protein synthesis. Diapausing embryos are resistant to environmental stress and survive months without oxygen (anoxia). A. limnaeus’ anoxia tolerance is an important survival mechanism as they can be buried in anoxic soil during development. Analysis of RNAseq data from diapausing A. limnaeus embryos show significant down-regulation of RGS2 transcripts in anoxic embryos. RGS2 regulates G-protein receptor signaling by inhibiting associated G_a-proteins and can inhibit protein synthesis. I hypothesis that …

Locating Vitamin D Receptors (Vdrs) In Annual Killifish, Austrofundulus Limnaeus, Rosalia N. Tanori, Amie L. Romney, Jason E. Podrabsky

Student Research Symposium

Austrofundulus limnaeus, a species of annual killifish found in unpredictable temporary habitats in South America, has a profound ability to survive long periods without water and oxygen. This tolerance is associated with the ability to enter metabolic dormancy associated with diapause. Entrance into diapause and tolerance of environmental stress is governed by an interplay of genetic and environmental factors. The vitamin D receptor (VDR) is among these factors and plays a crucial role in determining if an embryo will enter diapause or actively develop. My work aims to identify the genomic locations of VDR proteins in the A. limnaeus genome …

Annual Killifish: Eye Development And Retinal Cell Regeneration, Carmen Z. Rodriguez

Student Research Symposium

Vertebrate eye development is highly conserved. Current models have allowed the understanding of gene expression patterns that support eye development, but lack the context of extreme environmental conditions that challenge these fundamental programs. Typical vertebrate life spans can be years, but annual killifish, Austrofundulus limnaeus, are able to complete their entire adult lifespan in only weeks. Thus, A. limnaeus is a strong model for age-related macular degeneration. A. limnaeus also experiences embryonic diapause; a period of developmental dormancy. Developing/diapausing embryos of A. limnaeus are resistant to environmental stresses such as hypoxia/anoxia that would cause irreparable damage to vital organs, such …

Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier

Honors Scholar Theses

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles. In post-infectious hydrocephalus (PIH) cases, the condition presents challenges in understanding the immune response. PIH is a complex condition, often persisting after the initial infection is treated and thus requiring a deeper understanding of the immune mechanisms involved in its development. This thesis will explore the immunopathogenesis of PIH, elucidating the relationship between the immune response and neurological complications that would succeed infection. The immune response of PIH includes a series of events, beginning with the activation of immune cells and finishing with the release …

Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate …

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 …

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 …

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 …

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 …

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 …