Medical Cell Biology Commons^™

A Spatial Model Of Hepatic Calcium Signaling And Glucose Metabolism Under Autonomic Control Reveals Functional Consequences Of Varying Liver Innervation Patterns Across Species, Aalap Verma, Alexandra Manchel, Rahul Narayanan, Jan B. Hoek, Babatunde A Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Rapid breakdown of hepatic glycogen stores into glucose plays an important role during intense physical exercise to maintain systemic euglycemia. Hepatic glycogenolysis is governed by several different liver-intrinsic and systemic factors such as hepatic zonation, circulating catecholamines, hepatocellular calcium signaling, hepatic neuroanatomy, and the central nervous system (CNS). Of the factors regulating hepatic glycogenolysis, the extent of lobular innervation varies significantly between humans and rodents. While rodents display very few autonomic nerve terminals in the liver, nearly every hepatic layer in the human liver receives neural input. In the present study, we developed a multi-scale, multi-organ model of hepatic metabolism …

Metabolic Adaptation To The Chronic Loss Of Ca 2+ Signaling Induced By Ko Of Ip 3 Receptors Or The Mitochondrial Ca 2+ Uniporter, Michael P. Young, Zachary T Schug, David M. Booth, David I Yule, Katsuhiko Mikoshiba, György Hajnóczky, Suresh K Joseph

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IP3Rs) and the mitochondrial Ca2+ uniporter (MCU) are key proteins that regulate intracellular Ca2+ concentration. Mitochondrial Ca2+ accumulation activates Ca2+-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells. However, the interplay between calcium signaling and metabolism is not well understood. In this study, we used human cancer cell lines (HEK293 and HeLa) with stable KOs of all three IP3R isoforms (triple KO [TKO]) or MCU to examine metabolic and bioenergetic responses to the chronic …

Ethanol And Opioids Do Not Act Synergistically To Depress Excitation In Carotid Body Type I Cells, Ryan J. Rakoczy, Kajal Kamra, Yoon-Jae Yi, Christopher N. Wyatt

Neuroscience, Cell Biology & Physiology Faculty Publications

The combination of opioids and ethanol can synergistically depress breathing and the acute ventilatory response to hypoxia. Multiple studies have shown that the underlying mechanisms for this may involve calcium channel inhibition in central neurons. But we have previously identified opioid receptors in the carotid bodies and shown that their activation inhibits calcium influx into the chemosensitive cells. Given that the carotid bodies contribute to the drive to breathe and underpin the acute hypoxic ventilatory response, we hypothesized that ethanol and opioids may act synergistically in these peripheral sensory organs to further inhibit calcium influx and therefore inhibit ventilation.

Methods …

Mirna-30e Downregulation Increases Cancer Cell Proliferation, Invasion And Tumor Growth Through Targeting Rps6kb1, Lin Wang, Xiang-Bo Ji, Li-Hong Wang, Zhong-Kun Xia, Yun-Xia Xie, Wen-Jing Liu, Jian-Ge Qiu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Human esophagus carcinoma (EC) is one of the most common malignant tumors, especially in Africa and Asia including China. In EC initiation and progression, genetic and epigenetic aberrations have been reported to play a major role, but the underlying molecular mechanisms are largely unknown. In this study, the miR-30e levels were analyzed in human EC tissues and TCGA databases, and the results demonstrated that miR-30e expression in EC tissues was significantly decreased compared to adjacent normal tissues. To further investigate the role of miR-30e in cancer cells, we found that forced expression of miR-30e dramatically inhibited cell proliferation, invasion, tube …

Contact Normalization And The Role Of Maackia Amurensis Seed Lectin As A Novel Chemotherapeutic And Antiviral Agent, Stephanie A. Sheehan

Graduate School of Biomedical Sciences Theses and Dissertations

Cells communicate with each other to coordinate tissue function and homeostasis. Diseases including cancer, arthritis, and acute respiratory disease syndrome (ARDS) require a breakdown in this intercellular communication. For example, cancer progression is suppressed by junctional communication between nontransformed and transformed cells. This process is called contact normalization. Junctional communication must be disrupted to enable transformed cells to grow into malignancies. However, the junctions and mechanisms by which nontransformed cells normalize cell behavior have not been clearly defined. My project aimed to identify junctions and elucidate mechanisms underlying contact normalization. We discovered that cadherins, specifically N-cadherin, form junctions that enable …

The Molecular Mechanisms Of Estrogen Receptor Α On Two Single Nucleotide Polymorphisms To Regulate Wnt Signaling In Osteoblasts, Sarocha Suthon

Theses and Dissertations (ETD)

Osteoporosis is the most common bone metabolic disorder, affecting over 200 million people globally. It is characterized by bone mass depletion and microarchitectural deterioration, leading to bone fragility and susceptibility to bone fracture. Genetic factors, estrogen deficiency, and dysregulation of the WNT signaling pathway contribute to the development of this disease. Genome-wide association studies have predicted that the single nucleotide polymorphisms (SNPs) rs2887571 and rs9921222 associate with low bone mass, but the mechanism of these SNPs has remained unknown. Analysis of osteoblasts from 112 different joint replacement patients reveals that the genotype of rs2887571 correlates with WNT5B expression, and the …

Advancing Rna Virus Discovery And Biology With Whole Genome Sequencing, Mariah Katherine Taylor

Theses and Dissertations (ETD)

Two RNA virus families that pose a threat to human and animal health are Hantaviridae and Coronaviridae. These RNA viruses which originate in wildlife continue and will continue to cause disease, and hence, it is critical that scientific research define the mechanisms as to how these viruses spillover and adapt to new hosts to become endemic. One gap in our ability to define these mechanisms is the lack of whole genome sequences for many of these viruses. To address this specific gap, I developed a versatile amplicon-based whole-genome sequencing (WGS) approach to identify viral genomes of hantaviruses and severe acute …

Role Of Smad2 And Smad3 On Adipose Tissue Development And Function, Roshan Kumari

Theses and Dissertations (ETD)

Introduction: Obesity and its associated metabolic syndrome are major medical problems worldwide including United States. Adipose tissue is the primary site of energy storage, playing important roles in health. Adipose tissue also has other critical functions, producing adipocytokines and contributing to normal nutrient metabolism, which in turn play important roles in satiety, inflammation, and total energy homeostasis. Activin A and activin B play important roles in maintaining body composition and energy homeostasis. This dissertation highlights the role of activin/SMADs signaling in adipose tissue development, function, and maintenance.

SMAD2/3 proteins are downstream mediators of transforming growth factor-β (TGFβ) family signaling, including …

Simultaneous Brain And Intramedullary Spinal Abscesses In A Patient With Streptococcus Intermedius Infection, David P. Friedman, Joseph Desimone Jr, Aaron Christensen, Matthew Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A male patient in his thirties presented to the hospital with meningismus and altered mental status. Cerebrospinal fluid (CSF) analysis confirmed meningitis, but no microorganisms were identified. Head imaging (MRI) revealed multiple brain abscesses. Surgically-collected brain specimens revealed Gram-positive cocci and subsequently grew Streptococcus intermedius. MRI of the thoracic spine subsequently also identified an intramedullary spinal abscess. While brain abscesses and spinal abscesses caused by S. intermedius have been previously reported, the extent of disseminated disease in the patient was noteworthy.

An Investigative Analysis Of Underlying Alzheimer’S Disease Pathology: Understanding The Pathology Of Neurofibril Tangles, William Barker

Senior Honors Theses

Researchers familiar with Alzheimer’s Disease (AD) refer to two common pathological hallmarks: β-amyloid plaques and Neurofibril Tangles (NFTs). The development of these pathologies are the leading theory to explain the cause of cognitive decline and dementia-like symptoms of individuals with AD. The literature supports the theory that NFTs are caused by the hyperphosphorylation of the precursor tau protein. However, the mechanism that causes this hyperphosphorylation is still unknown. This review seeks to evaluate the normal function of tau then analyze and expound upon the current research concerning the underlying mechanisms for the hyperphosphorylation of tau observed in Neurofibril Tangles pathologies. …

The Role Of Hgf/Met Signaling In Metastatic Uveal Melanoma, Ryota Tanaka, Mizue Terai, Eric R Londin, Takami Sato

Department of Medical Oncology Faculty Papers

Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signaling promotes tumorigenesis and tumor progression in various types of cancer, including uveal melanoma (UM). The roles of HGF/MET signaling have been studied in cell survival, proliferation, cell motility, and migration. Furthermore, HGF/MET signaling has emerged as a critical player not only in the tumor itself but also in the tumor microenvironment. Expression of MET is frequently observed in metastatic uveal melanoma and is associated with poor prognosis. It has been reported that HGF/MET signaling pathway activation is the major mechanism of treatment resistance in metastatic UM (MUM). To achieve maximal therapeutic benefit …

Super-Resolution Microscopy Reveals Photoreceptor-Specific Subciliary Location And Function Of Ciliopathy-Associated Protein Cep290, Valencia L Potter, Abigail R Moye, Michael A Robichaux, Theodore G Wensel

Faculty, Staff and Students Publications

Mutations in the cilium-associated protein CEP290 cause retinal degeneration as part of multiorgan ciliopathies or as retina-specific diseases. The precise location and the functional roles of CEP290 within cilia and, specifically, the connecting cilia (CC) of photoreceptors, remain unclear. We used super-resolution fluorescence microscopy and electron microscopy to localize CEP290 in the CC and in the primary cilia of cultured cells with subdiffraction resolution and to determine effects of CEP290 deficiency in 3 mutant models. Radially, CEP290 localizes in close proximity to the microtubule doublets in the region between the doublets and the ciliary membrane. Longitudinally, it is distributed throughout …

Genetic Targeting Of Adult Renshaw Cells Using A Calbindin 1 Destabilized Cre Allele For Intersection With Parvalbumin Or Engrailed1, Alicia R. Lane, Indeara C. Cogdell, Thomas M. Jessell, Jay B. Bikoff, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Renshaw cells (RCs) are one of the most studied spinal interneurons; however, their roles in motor control remain enigmatic in part due to the lack of experimental models to interfere with RC function, specifically in adults. To overcome this limitation, we leveraged the distinct temporal regulation of Calbindin (Calb1) expression in RCs to create genetic models for timed RC manipulation. We used a Calb1 allele expressing a destabilized Cre (dgCre) theoretically active only upon trimethoprim (TMP) administration. TMP timing and dose influenced RC targeting efficiency, which was highest within the first three postnatal weeks, but specificity was low with …

Retinoic Acid Fluctuation Activates An Uneven, Direction-Dependent Network-Wide Robustness Response In Early Embryogenesis, Madhur Parihar, Liat Bendelac-Kapon, Michal Gur, Tali Abbou, Abha Belorkar, Sirisha Achanta, Keren Kinberg, Rajanikanth Vadigepalli, Abraham Fainsod

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Robustness is a feature of regulatory pathways to ensure signal consistency in light of environmental changes or genetic polymorphisms. The retinoic acid (RA) pathway, is a central developmental and tissue homeostasis regulatory signal, strongly dependent on nutritional sources of retinoids and affected by environmental chemicals. This pathway is characterized by multiple proteins or enzymes capable of performing each step and their integration into a self-regulating network. We studied RA network robustness by transient physiological RA signaling disturbances followed by kinetic transcriptomic analysis of the recovery during embryogenesis. The RA metabolic network was identified as the main regulated module to achieve …

Nsaids Naproxen, Ibuprofen, Salicylate, And Aspirin Inhibit Trpm7 Channels By Cytosolic Acidification, Rikki Chokshi, Orville Bennett, Tetyana Zhelay, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for relieving pain and inflammation accompanying numerous disease states. The primary therapeutic mechanism of these widely used drugs is the inhibition of cyclooxygenase 1 and 2 (COX1, 2) enzymes that catalyze the conversion of arachidonic acid into prostaglandins. At higher doses, NSAIDs are used for prevention of certain types of cancer and as experimental treatments for Alzheimer’s disease. In the immune system, various NSAIDs have been reported to influence neutrophil function and lymphocyte proliferation, and affect ion channels and cellular calcium homeostasis. Transient receptor potential melastatin 7 (TRPM7) cation channels are highly expressed in …

M6a Associated Tsuc7 Inhibition Contributed To Erlotinib Resistance In Lung Adenocarcinoma Through A Notch Signaling Activation Dependent Way, Kai Li, Zi-Yang Peng, Shan Gao, Qing-Shi Wang, Rui Wang, Xiang Li, Guo-Dong Xiao, Jing Zhang, Hong Ren, Shou-Ching Tang, Xin Sun

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: The small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects.

Methods: Multiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections.

Results: We explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of YTHDF2 …

Therapeutic Efficacy Of Mesenchymal Stem Cells For Cardiovascular Diseases, Dragana Radoje Miloradovic, Dragica Radoje Pavlovic, Miodrag Bozidar Stojkovic, Sanja Bratislav Bojic, Vladislav Bogdan Volarevic, Marina Milosav Gazdic Jankovic, Biljana Tomislav Ljujic

Journal of Mind and Medical Sciences

Despite the improvements in pharmacological and surgical treatments, cardiovascular diseases (CVDs) are the number one cause of death worldwide. During the last two decades, the search for new therapies has been revolutionized with the growing knowledge of stem cell biology. Due to their huge differentiation capacity and paracrine effects, mesenchymal stem cells (MSCs) are a promising tool for the treatment of CVDs. The encouraging outcomes of preclinical studies using MSCs as a treatment for diseased myocardium have set the scene for worldwide clinical trials. In this review, we overview either complete or ongoing clinical trials using MSCs for the therapy …

Cell-Based Therapies For Retinal Diseases: A Review Of Clinical Trials And Direct To Consumer "Cell Therapy" Clinics, John Hinkle, Raziyeh Mahmoudzadeh, Ajay E. Kuriyan

Wills Eye Hospital Papers

Background: The retinal pigment epithelium (RPE) is implicated in the pathophysiology of many retinal degenerative diseases. This cell layer is also an ideal target for cell-based therapies. Several early phase clinical trials evaluating cell therapy approaches for diseases involving the RPE, such as age-related macular degeneration and Stargardt's macular dystrophy have been published. However, there have also been numerous reports of complications from unproven "cell therapy" treatments marketed by "cell therapy" clinics. This review aims to outline the particular approaches in the different published clinical trials for cell-based therapies for retinal diseases. Additionally, the controversies surrounding experimental treatments offered outside …

Understanding The Effect Of Dietary Palmitic Acid On Glycolysis During Innate Immune Memory In Macrophages, Khaleda A. Aqaei

University Honors Theses

Trained immunity is long-term innate immune memory induced by a primary stimulus, which leads to hyper-inflammation upon secondary stimulation with a homologous or heterologous ligand. Trained immunity is mediated by epigenetic and metabolic reprogramming of the target cell and leads to modification of gene expression and cellular function. Classically, trained immunity is initiated by β-glucans, an inflammatory molecule found on the exterior of fungal species. Interestingly, our lab has recently described that dietary fatty acids can initiate trained immunity, working through similar pathways as β-glucans. Specifically, our data show that a pre-treatment with a specific dietary saturated fatty acid (SFA), …

Gβγ Regulates Mitotic Golgi Fragmentation And G2/M Cell Cycle Progression., Kalpana Rajanala, Lauren M. Klayman, Philip B. Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins (αβγ) function at the cytoplasmic surface of a cell's plasma membrane to transduce extracellular signals into cellular responses. However, numerous studies indicate that G proteins also play noncanonical roles at unique intracellular locations. Previous work has established that G protein βγ subunits (Gβγ) regulate a signaling pathway on the cytoplasmic surface of Golgi membranes that controls the exit of select protein cargo. Now, we demonstrate a novel role for Gβγ in regulating mitotic Golgi fragmentation, a key checkpoint of the cell cycle that occurs in the late G2 phase. We show that small interfering RNA-mediated depletion of …

Alveolar Socket Healing In 5-Lipoxygenase Knockout Aged Female Mice Treated Or Not With High Dose Of Zoledronic Acid, Ramez H Mahmoud, Claudia C Biguetti, Gustavo B Simionato, Isabela C Custódio, Raquel B P Silva, Marco A H Duarte, Leonardo P Faverani, Edilson Ervolino, Walid D Fakhouri, Mariza A Matsumoto

Faculty, Staff and Student Publications

This study investigated the role 5-lypoxigenase (5-LO) on alveolar socket healing in aged female mice treated with zoledronic acid (ZL). Forty 129/Sv female mice (64-68 weeks old), 20 wild type (WT) and 20 5-LO knockout (5LOKO) were equally distributed according to ZL treatment: WT Control, WT ZL, 5LOKO Control, and 5LOKO ZL. ZL groups were treated with an intraperitoneal injection of 250 µg/Kg of ZL, while controls were treated with saline. Treatments were administered once a week, starting four weeks before surgery for tooth extraction and until 7 and 21 days post-surgery. Mice were euthanized for a comprehensive microscopic analysis …

Clinically Relevant Dosage Of Vancomycin Does Not Negatively Impact Periosteum Derived Osteoblast Precursor Cellular Functions, Alexis Hernandez

Seton Hall University Dissertations and Theses (ETDs)

Surgical site infections (SSI) can develop post-operatively and carry significant clinical and financial implications. SSI can carry a cost of up to $30,000 per case, as well as an estimated 6 day longer hospitalization. Patients with Type II Diabetes (DM) have an increased susceptibility to infection and suffer from poor bone healing overall. Therefore, diabetic patients who have undergone orthopedic surgery risk both an increased chance of developing an SSI as well as suboptimal bone healing. Vancomycin and other antibiotics have traditionally been used prophylactically to prevent infection, however the effect of vancomycin on bone healing in a diabetic population …

Placenta-Specific Slc38a2/Snat2 Knockdown Causes Fetal Growth Restriction In Mice, Owen R. Vaughan, Katarzyna Maksym, Elena Silva, Kenneth Barentsen, Russel V. Anthony, Sara L. Hillman, Thomas L. Brown, Rebecca Spencer, Anna L. David, Fredrick J. Rosario, Theresa L. Powell, Thomas Jansson

Neuroscience, Cell Biology & Physiology Faculty Publications

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of …

Exogenous Inter-Α Inhibitor Proteins Prevent Cell Death And Improve Ischemic Stroke Outcomes In Mice, Louise D Mccullough, Meaghan Roy-O'Reilly, Yun-Ju Lai, Anthony Patrizz, Yan Xu, Juneyoung Lee, Aleah Holmes, Daniel C Kraushaar, Anjali Chauhan, Lauren H Sansing, Barbara S Stonestreet, Liang Zhu, Julia Kofler, Yow-Pin Lim, Venugopal Reddy Venna

Faculty, Staff and Students Publications

Inter-α inhibitor proteins (IAIPs) are a family of endogenous plasma and extracellular matrix molecules. IAIPs suppress proinflammatory cytokines, limit excess complement activation, and bind extracellular histones to form IAIP-histone complexes, leading to neutralization of histone-associated cytotoxicity in models of sepsis. Many of these detrimental processes also play critical roles in the pathophysiology of ischemic stroke. In this study, we first assessed the clinical relevance of IAIPs in stroke and then tested the therapeutic efficacy of exogenous IAIPs in several experimental stroke models. IAIP levels were reduced in both ischemic stroke patients and in mice subjected to experimental ischemic stroke when …

Comparative Analysis Of Proteomics Biomarkers Associated With Residual Ridge Resorption Induced By Denture Wear, Rohana Ahmad, Ainin Sofia Mohamad Napi, Tong Wah Lim, Su Keng Tan, Saiful Anuar Karsani, Musalmah Mazlan, Lay Kek Teh, Steven M. Morgano, Nadim Z. Baba

Makara Journal of Health Research

Background: The biochemical bone turnover markers for residual ridge resorption (RRR) are unclear. Therefore, the present study aimed to determine the biochemical bone turnover markers associated with RRR by comparing proteomics between the compressed mucosa of denture wearers and the non-compressed mucosa of non-denture wearers.

Methods: The mucosal specimens of 11 complete-denture wearers were obtained from the alveolar ridge during surgical implant exposure for implant-retained overdentures. All denture wearers had been edentulous and worn dentures for at least 5 years. The tissues of 11 non-denture wearers were taken from the ridge during minor preprosthetic surgery. The mucosal proteins …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Intensity-Dependent Changes In Quantified Resting Cerebral Perfusion With Multiple Sessions Of Transcranial Dc Stimulation, Matthew Sherwood, Lindsey Mcintire, Aaron T. Madaris, Kamin Kim, Charan Ranganath, R. Andy Mckinley

Neuroscience, Cell Biology & Physiology Faculty Publications

Transcranial direct current stimulation (tDCS) to the left prefrontal cortex has been shown to produce broad behavioral effects including enhanced learning and vigilance. Still, the neural mechanisms underlying such effects are not fully understood. Furthermore, the neural underpinnings of repeated stimulation remain understudied. In this work, we evaluated the effects of the repetition and intensity of tDCS on cerebral perfusion [cerebral blood flow (CBF)]. A cohort of 47 subjects was randomly assigned to one of the three groups. tDCS of 1- or 2-mA was applied to the left prefrontal cortex on three consecutive days, and resting CBF was quantified before …

Investigations In The Cellular And Molecular Biology Of Human Airway Mucociliary Tissue, Vincent Manna

Graduate School of Biomedical Sciences Theses and Dissertations

Our laboratory has integrated the use of a human-derived, in vitro model of airway mucociliary tissue. We isolate human nasal epithelial cells (HNECs) from the nasal mucociliary tissue of donors with a small brush and expand the airway progenitor cells in culture. The HNECs are then seeded onto semi-permeable transwell inserts. The inserts are in contact with the media in the lower chamber but don’t contain media in the upper chamber therefore the cells are exposed to the air while drawing nutrients from the media below, this is called the Air-Liquid Interface (ALI). HNECs cultured at the ALI initiate a …

Vascular Disease Pathogenesis In Smooth Muscle Dysfunction Syndrome And Majewski Osteodysplastic Primordial Dwarfism Type Ii, Jamie Wright

Dissertations and Theses (Open Access)

Vascular diseases are a leading cause of morbidity and mortality world-wide. Understanding their pathogenesis is crucial to better diagnosis and management of these life-threatening conditions. Through the study of rare mutations that lead to early onset and severe vascular diseases, we can elucidate underlying mechanisms for vascular disease pathogenesis and develop better treatments to prevent and manage more common causes of vascular diseases. In this study we look at two rare diseases that lead to severe vascular phenotypes, Smooth Muscle Dysfunction Syndrome (SMDS) and Majewski Osteodysplastic Primordial Dwarfism Type II (MOPDII). SMDS is a rare condition due to pathogenic variants …

Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas

Graduate Theses/Dissertations

Extracellular nucleotides (ATP, UTP) released from cells act on nucleotide receptors to promote vascular inflammation. Increased leukocyte-endothelial interaction is a hallmark of vascular inflammation. The nucleotide P2Y₂ receptor (P2Y₂R), activated by extracellular ATP≈UTP, plays a role in cardiovascular homeostasis and immune regulation. Moreover, accumulating evidence from studies in vitro and in vivo models have implicated the P2Y₂R in the inflammatory response significantly contributing to the progression and pathogenesis of asthma, atherosclerosis, sepsis, and ischemia. I hypothesized that P2Y₂R activation by UTP, an agonist of the receptor, increased leukocyte rolling and adhesion in the microvasculature from baseline. To test the hypothesis, …