Cell and Developmental Biology Commons^™

Repressive Interactions Between Transcription Factors Separate Different Embryonic Ectodermal Domains., Steven L. Klein, Andre L P Tavares, Meredith Peterson, Charles H Sullivan, Sally A. Moody

Anatomy and Regenerative Biology Faculty Publications

The embryonic ectoderm is composed of four domains: neural plate, neural crest, pre-placodal region (PPR) and epidermis. Their formation is initiated during early gastrulation by dorsal-ventral and anterior-posterior gradients of signaling factors that first divide the embryonic ectoderm into neural and non-neural domains. Next, the neural crest and PPR domains arise, either

Evaluation Of Cell-Matrix Interactions In K14+ Leader Cells On Caf-Modulated Matrix, Trey P. Redman, Jessanne Y. Lichtenberg, Priscilla Y. Hwang

Summer REU Program

No abstract provided.

Predicting Gene Function Of Unknown Yeast Orfs Through Phylogenetic Comparative Analysis, Lewis Barr

Graduate Research Showcase

Yeast (Saccharomyces cerevisiae) has been an instrumental model system for an extraordinary diverse array of research applications for over a century now. The S. cerevisiae genome was fully sequenced in 1996, and, as a result, 6,753 potential proteins were identified. These putative proteins were established by investigating likely open reading frames within the genome. Over the past few decades, nearly 5,000 open reading frames (ORFs) and their expressed proteins have been described, and the remaining undefined open reading frames are labeled as open reading frames of unknown function (ORFans). To better understand the remaining gaps within the S. …

The Role Of Ehd2 In Endothelial Cells, Rachael Judson

Electronic Theses and Dissertations

The role of EHD2 in terms of Cav1 interaction had not been previously characterized and was the main goal of this research. Cav1 has been shown to lead to the ubiquitination of Rac1. Because of this, the role of EHD2 in Rac1 regulation was investigated. An increase in long-term migration in endothelial cells was observed and suggested that EHD2 impacts the RhoA pathway instead of the Rac1 pathway. This lead to the hypothesis that EHD2 controls a part of the RhoA pathway. This hypothesis is supported by the loss of filamentous actin and an increase in serrated junctions in cells …

Inhibition Of De Novo And The Prion-Like Spread Of Amyloidogenesis Using In Vitro And In Vivo Disease Models, Johnson Anazoba Joseph

Electronic Theses and Dissertations

The aberrant fibrous, extracellular, and intracellular proteinaceous deposits in cells, organs and tissues are referred to as amyloids. These deposits are dominated by β-sheet structures that have been implicated in several neurodegenerative diseases and cancer. In this work, the types of amyloidosis studied include Parkinson’s disease (PD) using UA196 and NL5901 strains of Caenorhabditis elegans (C. elegans), Alzheimer’s disease (AD) using GMC101 strain of C. elegans, and cancer-associated mutant p53 aggregation in MIA PaCa-2 mutant cells. Several molecules including SK-129, NS132, NS163, bexarotene, a polyphenol (-)-epi-gallocatechine gallate (EGCG), ADH40, RD148, and RD242 were screened in vitro and in …

Extracellular Vesicles And Lipid Flippase Regulators In C. Elegans, Lauren Pitts

Electronic Theses and Dissertations

Extracellular vesicles (EVs) are membrane derived organelles released by all cell types and carry a vast array of cargos that can influence communication, development, and disease. One type of EV, known as microvesicles, form by budding directly from the plasma membrane in a process known as ectocytosis, however the mechanisms that govern this process are poorly understood. In C. elegans, the P4-ATPase, TAT-5, along with its activator, PAD-1, inhibit EV release from the plasma membrane by inhibiting phosphatidylethanolamine (PE) exposure on the outer leaflet of the plasma membrane. We identified 3 key domains of PAD-1 that are required to inhibit …

The Pathophysiological Mechanisms Of Alzheimer's Disease; Investigating Therapeutic Interventions For Disease Onset, Alexandra A. Sandberg

Electronic Theses and Dissertations

Alzheimer’s Disease is a multifarious disease that progressively affects more people as both the proportion of older adults in the population and life expectancy increase in both the United States and worldwide. This devastating disease is a result of rampant neuronal loss in the memory centers of the brain that robs the independence of those who are diagnosed and places a heavy burden on those who care for them. Traditionally speaking, research has focused on the hallmark pathology of amyloid plaques, targeting them to try and prevent disease onset. However, countless failures in clinical trials aimed at this said pathology …

Mutations Linked To Rare Diseases Can Be Generated And Tested In Zebrafish, Brianna Jansen, Luke Schipper, Valeria Lacroix, Amy Wilstermann, Rachael Baker

Summer Research

• BCS1L is important for cellular respiration and located in the mitochondria.
• Mutations in BCS1L cause a wide variety of symptoms leading to 3 rare diseases.

Preferential Infection Of Ccr6+ Cd4+ T Cells By Hiv Is Increased By Human Intestinal Endothelial Cells, Fisher Pham, Jessica Eddy, Nathan Dapprich, Anding Shen

Summer Research

Th17 cells are found to be heavily depleted in the gut of HIV patients. Even after successful antiretroviral therapy, HIV patients exhibit a smaller Th17 population for years after treatment. Previous research has found human intestinal endothelial cells (IEC) to increase HIV infection of helper T cells. Using CCR6 as a marker for Th17, we investigated the effect of IEC on HIV infection of Th17 cells. IECs were found to increase the preferential infection of resting and activated CCR6+ cells. Th17 cells are known to be more susceptible to HIV infection than other types of CD4+ T cells. IEC stimulation …

Antioxidant Biomarkers And Nutraceutical Therapeutics In Neurodegeneration And Neurotrauma, Lilia A. Koza

Electronic Theses and Dissertations

Mild traumatic brain injury (mTBI), yielding a Glascow Coma Scale of 13-15, is the most commonly occurring severity of TBI. Pathology from mTBI consists of blood brain barrier disruption, neuroinflammation, oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal degeneration, and resulting neuronal death. These processes deplete the body’s endogenous antioxidant system. We report a retrospective analysis of antioxidant blood biomarkers in patients with a history of mTBI from a local sports medicine clinic, Resilience Code. We found persistent sex-specific antioxidant depletions in mTBI patients associated with worsened symptomology.

Certain populations, such as athletes, are at high risk for repetitive mTBI …

Organellar Zn2+ Homeostasis And The Role Of Trpml Channels In Neuronal Lysosome Physiology And Axonal Transport, Taylor Franklin Minckley

Electronic Theses and Dissertations

Zinc (Zn²⁺) is crucial for proper cellular function, and as such it is important to measure and track Zn²⁺ dynamics in living cells. Fluorescent sensors have been used to estimate Zn²⁺ content of subcellular compartments, but little is known about endolysosomal Zn2+ homeostasis. Similarly, although numerous sensors have been reported, it is unclear whether and how Zn²⁺ can be released from intracellular compartments into the cytosol due to a lack of probes that can detect physiological dynamics of cytosolic Zn²⁺. My dissertation started with comparing and characterizing different Zn²⁺ sensors including the …

The Effects Of Neuronal Growth Factors On Lps-Activated Schwann Cells, Caitlyn E. Henry, Peyton Kimmel, Angela Asirvatham Ph.D.

Student Research Poster Presentations 2022

Schwann cells (SCs) are the principal support cells of neurons in the peripheral nervous system, that both myelinate axons for the rapid conduction of electrical impulses as well as assist in axonal repair during nerve injury. During nerve injury, SCs secrete tumor necrosis factor alpha (TNF-α)^1,5,6 and other proinflammatory mediators^1,6, attracting macrophages to the site of injury to induce inflammation and clear myelin debris.^1,6 Once the debris is cleared, the neuron stimulates SC proliferation by secreting neuronal mitogens, such as heregulin^3,4, and an unknown factor that activates the cAMP pathway³, an important …

Simulation Of An Inflammatory Model Using Schwann Cells, Caitlyn Henry, Peyton Kimmel, Angela Asirvatham

Student Research Poster Presentations 2022

During peripheral nerve injury, the myelin surrounding the neuronal axons is damaged, initiating an inflammatory response to remove myelin debris. Once myelin debris is cleared, Schwann cells acquire a proliferating phenotype which allows them to grow and divide so that remyelination can occur. The neuron stimulates Schwann cell division by secreting growth factors, like heregulin, and an unknown growth factor that activates the cAMP pathway. Although the role of cAMP in axonal regeneration is well-known, not much has been explored about its function in Schwann cells during nerve injury and inflammation. To simulate an inflammatory environment, the S16 Schwann cell …

Generalizing Frameworks For Sentience Beyond Natural Species, Michael Levin

Animal Sentience

Crump et al. (2022) offer a well-argued example of an essential development: a rigorous framework for assessing sentience from the perspective of moral concern over an agent’s welfare. Current and forthcoming developments in bioengineering, synthetic morphology, artificial intelligence, biorobotics, and exobiology necessitate an expansion and generalization of this effort. Verbal reports (the Turing Test) and homology to human brains are utterly inadequate criteria for assessing the status of novel, unconventional agents that offer no familiar touchstone of phylogeny or anatomy. We must develop principled approaches to evaluating the sentience of (and thus, our responsibility to) beings of unfamiliar provenance and …

A Novel Chelator For Pb-212/Bi-212-Based Alpha-Particle Radiotherapy For Cancers, Eric Doorn, Mengshi Li, Brianna Cagle, Nicholas Baumhover, Zhiming Dai, Dijie Liu, Ivy Vance, Frances Johnson, Michael K. Schultz

Summer Research

Lead-212 ( 212Pb) has been identified as a promising candidate for alpha(α)- particle radiotherapies for cancers in preclinical and clinical studies. Using a low molecular weight peptide, the radiotherapy will target with high affinity selective markers highly expressed in cancer cells but found in low concentration in healthy tissue. A radiometal is coupled to a chelator moiety linked to the peptide to deliver the α-particle radiation destroying cancer cells.

To develop a novel Pb specific chelator (PSC) that will provide high affinity to Pb212 and improve the in vitro and in vivo binding pharmacokinetics and stability of progeny of the …

Exploring The Role Of Ahr Activation In Bladder Cancer Models, Hyeon Jin Kim, Peter Jones, Josh Jang, Justin Kulchycki

Summer Research

Immune checkpoint inhibitor therapy was designed to reinvigorate immune cells to bind and kill cancer cells. However, the treatment that was intended to help patients resulted in hyper progressive disease (when the tumor shows accelerated growth, leading to an explosion of tumor growth in a short period of time). We searched for a particular gene that could function as a biomarker for hyperprogression. Upon inspecting tumor samples, we discovered a biomarker called CYP1A1. We thought to test if a tumor that expressed high levels of endogenous CYP1A1, treated with immunotherapy, ultimately led to hyper progression. Every step of the project …

Targeting Histone Reader Enl With Protac Degrader, Josiah Harsh, Zhaoyu Xue, Fan Xuan, Xiaobing Shi, Hong Wen

Summer Research

ENL is a histone reader that is part of the super elongation complex and is primarily involved in chromatin and gene expression regulation. ENL has also been found to play an essential role in the progression of a spectrum of acute myeloid leukemia (AML). Some hotspot mutations of its reader module, the YEATS domain, have been found to be oncogenic. For this reason, we explored the efficacy of a newly developed ENL PROTAC degrader in its ability to degrade wild-type and mutant ENL protein and suppress oncogene expression in cancer cells.

The Role Of Integrins In Hiv-1 Infection Of Intestinal Endothelial Cell Stimulated Resting Cd4+ T Cells, Jessica Eddy, Fisher Pham, Nathan Dapprich, Anding Shen

Summer Research

A major barrier to eradicating HIV is latent reservoirs in resting CD4+ T cells. Antiretroviral therapy is effective in bringing the viral load down to undetectable levels but is unable to eradicate the latent reservoir. Previous data from our lab revealed that when stimulated by intestinal endothelial cells (IEC), resting CD4+ T cells can be directly infected while remaining in a resting state, allowing formation of latent reservoirs. An additional study found that integrins, which are cell surface molecules, play a role in the interactions between endothelial cells (EC) and T cells. Our research further examines the role of integrins …

A Tale Of Two Toxicants: How Trichloroethylene (Tce) And Perchloroethylene (Pce) Metabolites Affect Immune Cell Viability Upon Co-Exposure With Lipopolysaccharide (Lps), Eleanor Scheeres, Sean Harris, Erica Boldenow

Summer Research

• TCE and PCE are volatile organic solvents used in industrial processes, such as metal degreasing and dry cleaning, and known human carcinogens.
• GBS is a common bacteria in the vaginal flora but can lead to complications such as preterm birth during pregnancy.
• Lipopolysaccharide (LPS) is a gram-negative bacterial cell wall component that induces inflammatory immune responses and is used as an infection model.
• Co-treatment (GBS+DCVC) in placental membranes lead to inhibition of pathogen stimulated cytokine secretion (Fig. 1).
• We hypothesized that DCVC and TCVC (PCE’s metabolite) would produce decreased cell viability, and DCVC+LPS would produce further immune inhibitory effects, which …

Er-Golgi In Membrane Repair In Cardiomyocytes, Visakuo Tsurho, Hsin-Yu Chen, Daniel Michele

Summer Research

Impaired membrane repair leads to muscular dystrophies like Miyoshi Myopathy and LGMD2B1. The mechanism behind membrane repair is not well understood, and there are few studies on membrane repair in cardiomyocytes. Research in nonmuscle cells suggest that lysosomes are a source of membranes for repairing injuries2. Few lysosomes were found in cardiomyocytes compared to non cardiomyocytes. Therefore, we investigated the ER and Golgi as potential organelles involved in membrane repair in cardiomyocytes. We used Sec22b to investigate ER to Golgi in membrane repair in cardiomyocytes because it is an ER-Golgi protein involved in membrane fusion and Golgi vesicle trafficking in …