Biochemistry, Biophysics, and Structural Biology Commons^™

Chronic Kidney Disease Promotes Atrial Fibrillation Via Inflammasome Pathway Activation, Jia Song, Jose Alberto Navarro-Garcia, Jiao Wu, Arnela Saljic, Issam Abu-Taha, Luge Li, Satadru K Lahiri, Joshua A Keefe, Yuriana Aguilar-Sanchez, Oliver M Moore, Yue Yuan, Xiaolei Wang, Markus Kamler, William E Mitch, Gema Ruiz-Hurtado, Zhaoyong Hu, Sandhya S Thomas, Dobromir Dobrev, Xander Ht Wehrens, Na Li

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) is associated with a higher risk of atrial fibrillation (AF). The mechanistic link between CKD and AF remains elusive. IL-1β, a main effector of NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, is a key modulator of conditions associated with inflammation, such as AF and CKD. Circulating IL-1β levels were elevated in patients with CKD who had AF (versus patients with CKD in sinus rhythm). Moreover, NLRP3 activity was enhanced in atria of patients with CKD. To elucidate the role of NLRP3/IL-1β signaling in the pathogenesis of CKD-induced AF, Nlrp3-/- and WT mice were subjected to …

Kinome Reprogramming Is A Targetable Vulnerability In Esr1 Fusion-Driven Breast Cancer, Xuxu Gou, Beom-Jun Kim, Meenakshi Anurag, Jonathan T Lei, Meggie N Young, Matthew V Holt, Diana Fandino, Craig T Vollert, Purba Singh, Mohammad A Alzubi, Anna Malovannaya, Lacey E Dobrolecki, Michael T Lewis, Shunqiang Li, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen-binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs. Subsequent explorations of drug sensitivity validated RET kinase as a common therapeutic vulnerability despite remarkable ESR1-TAF C-terminal sequence and structural diversity. Organoids and xenografts from a pan-ET-resistant patient-derived xenograft model that harbors the ESR1-e6>YAP1 TAF were …

Type 1 Diabetes Genetic Risk Score Differentiates Subgroups Of Ketosis-Prone Diabetes, Deborah Osafehinti, Surya N Mulukutla, Christiane S Hampe, Ruchi Gaba, Nalini Ram, Michael N Weedon, Richard A Oram, Ashok Balasubramanyam

Faculty, Staff and Students Publications

OBJECTIVE: To determine whether genetic risk for type 1 diabetes (T1D) differentiates the four Aβ subgroups of ketosis-prone diabetes (KPD), where A+ and A- define the presence or absence of islet autoantibodies and β+ and β- define the presence or absence of β-cell function.

RESEARCH DESIGN AND METHODS: We compared T1D genetic risk scores (GRS) of patients with KPD across subgroups, race/ethnicity, β-cell function, and glycemia.

RESULTS: Among 426 patients with KPD (54% Hispanic, 31% African American, 11% White), rank order of GRS was A+β- > A+β+ = A-β- > A-β+. GRS of A+β- KPD was lower than that of a T1D …

Hpv Imprints In Western India: The Overlooked Criteria For Cancer Profiling, Ashi R. Thobias, Jayendra B. Patel, Prabhudas P. Patel

Research Symposium

Background: In India, HPV infection detection for cancer-typing has been largely evaded. Especially, data on prevalence of HPV types other than the highly prevalent HPV 16 and 18 are lacking, particularly from the western region. Thus, present study aimed to evaluate prevalence of HPV strains in three most prevailing cancers in India i.e. cervical, oral and oropharyngeal cancer.

Materials & methods: DNA was isolated from tissue samples of 400 cervical cancer cases, 127 oral cancer cases and 75 oropharyngeal cancer cases and endpoint PCR was performed using degenerative primers MY 09/11, GP 5+/6+ and CP I/II. TS-PCR was conducted to …

Vadadustat For Treatment Of Anemia In Patients With Dialysis-Dependent Chronic Kidney Disease Receiving Peritoneal Dialysis, Mark J Sarnak, Rajiv Agarwal, Neil Boudville, Pradip C P Chowdhury, Kai-Uwe Eckardt, Carlos R Gonzalez, Laura A Kooienga, Mark J Koury, Kwabena A Ntoso, Wenli Luo, Patrick S Parfrey, Dennis L Vargo, Wolfgang C Winkelmayer, Zhiqun Zhang, Glenn M Chertow

Faculty, Staff and Students Publications

BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear.

METHODS: We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular …

The Transcription Factor Chrebp Links Mitochondrial Lipidomes To Mitochondrial Morphology And Progression Of Diabetic Kidney Disease, Li Li, Jianyin Long, Koki Mise, Naravat Poungavrin, Philip L Lorenzi, Iqbal Mahmud, Lin Tan, Pradip K Saha, Yashpal S Kanwar, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

A substantial body of evidence has established the contributions of both mitochondrial dynamics and lipid metabolism to the pathogenesis of diabetic kidney disease (DKD). However, the precise interplay between these two key metabolic regulators of DKD is not fully understood. Here, we uncover a link between mitochondrial dynamics and lipid metabolism by investigating the role of carbohydrate-response element-binding protein (ChREBP), a glucose-responsive transcription factor and a master regulator of lipogenesis, in kidney podocytes. We find that inducible podocyte-specific knockdown of ChREBP in diabetic db/db mice improves key biochemical and histological features of DKD in addition to significantly reducing mitochondrial fragmentation. …

Early Detection Of Lung Cancer Using Artificial Intelligence-Enhanced Optical Nanosensing Of Chromatin Alterations In Field Carcinogenesis, Ali Daneshkhah, Sravya Prabhala, Parvathi Viswanathan, Hariharan Subramanian, Jianan Lin, Andrew S Chang, Ankit Bharat, Hemant Kumar Roy, Vadim Backman

Faculty, Staff and Students Publications

Supranucleosomal chromatin structure, including chromatin domain conformation, is involved in the regulation of gene expression and its dysregulation has been associated with carcinogenesis. Prior studies have shown that cells in the buccal mucosa carry a molecular signature of lung cancer among the cigarette-smoking population, the phenomenon known as field carcinogenesis or field of injury. Thus, we hypothesized that chromatin structural changes in buccal mucosa can be predictive of lung cancer. However, the small size of the chromatin chain (approximately 20 nm) folded into chromatin packing domains, themselves typically below 300 nm in diameter, preclude the detection of alterations in intradomain …

Clinical Predictors And Outcomes After Left Ventricular Assist Device Implantation And Tracheostomy, Harveen K Lamba, Lucy D Hart, Qianzi Zhang, Jackquelin M Loera, Andrew B Civitello, Ajith P Nair, Mourad H Senussi, Gabriel Loor, Kenneth K Liao, Alexis E Shafii, Subhasis Chatterjee

Faculty, Staff and Students Publications

BACKGROUND: Postoperative respiratory failure is a major complication that affects up to 10% of patients who undergo cardiac surgery and has a high in-hospital mortality rate. Few studies have investigated whether patients who require tracheostomy for postoperative respiratory failure after continuous-flow left ventricular assist device (CF-LVAD) implantation have worse survival outcomes than patients who do not.

OBJECTIVE: To identify risk factors for respiratory failure necessitating tracheostomy in CF-LVAD recipients and to compare survival outcomes between those who did and did not require tracheostomy.

METHODS: Consecutive patients who underwent primary CF-LVAD placement at a single institution between August 1, 2002, and …

A Defective Mechanosensing Pathway Affects Fibroblast-To-Myofibroblast Transition In The Old Male Mouse Heart, Aude Angelini, Joann Trial, Alexander B Saltzman, Anna Malovannaya, Katarzyna A Cieslik

Faculty, Staff and Students Publications

The cardiac fibroblast interacts with an extracellular matrix (ECM), enabling myofibroblast maturation via a process called mechanosensing. Although in the aging male heart, ECM is stiffer than in the young mouse, myofibroblast development is impaired, as demonstrated in 2-D and 3-D experiments. In old male cardiac fibroblasts, we found a decrease in actin polymerization, α-smooth muscle actin (α-SMA), and Kindlin-2 expressions, the latter an effector of the mechanosensing. When Kindlin-2 levels were manipulated via siRNA interference, young fibroblasts developed an old-like fibroblast phenotype, whereas Kindlin-2 overexpression in old fibroblasts reversed the defective phenotype. Finally, inhibition of overactivated extracellular regulated kinases …

Dual Antiplatelet Therapy: A Concise Review For Clinicians, Hafeez Ul Hassan Virk, Johao Escobar, Mario Rodriguez, Eric R Bates, Umair Khalid, Hani Jneid, Yochai Birnbaum, Glenn N Levine, Sidney C Smith, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Dual antiplatelet therapy (DAPT) combines two antiplatelet agents to decrease the risk of thrombotic complications associated with atherosclerotic cardiovascular diseases. Emerging data about the duration of DAPT is being published continuously. New approaches are trying to balance the time, benefits, and risks for patients taking DAPT for established cardiovascular diseases. Short-term dual DAPT of 3-6 months, or even 1 month in high-bleeding risk patients, is equivalent in terms of efficacy and effectiveness compared to long-term DAPT for patients who experienced percutaneous coronary intervention in an acute coronary syndrome setting. Prolonged DAPT beyond 12 months reduces stent thrombosis, major adverse cardiovascular …

Circular Rna As Therapeutic Targets In Atherosclerosis: Are We Running In Circles?, Jeffrey Triska, Christo Mathew, Yang Zhao, Yuqing E Chen, Yochai Birnbaum

Faculty, Staff and Students Publications

Much attention has been paid lately to harnessing the diagnostic and therapeutic potential of non-coding circular ribonucleic acids (circRNAs) and micro-RNAs (miRNAs) for the prevention and treatment of cardiovascular diseases. The genetic environment that contributes to atherosclerosis pathophysiology is immensely complex. Any potential therapeutic application of circRNAs must be assessed for risks, benefits, and off-target effects in both the short and long term. A search of the online PubMed database for publications related to circRNA and atherosclerosis from 2016 to 2022 was conducted. These studies were reviewed for their design, including methods for developing atherosclerosis and the effects of the …

Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …

Amyloid-Beta Protein Concentration Dependence Of Reversible Aggregation Using Gold Colloid Particles, Renee Spencer, Lila Kocieniewski, Bryan Martinez, Kazushige Yokoyama

McNair Scholars Program

Although Alzheimer’s and COVID-19 are different diseases, the commonality between them is during the process of them developing in a person by fibrillogenesis. The product of fibrillogenesis results in the development of these diseases. We study the first stage of fibrillogenesis where the amyloid-beta peptide monomers are assembled into an oligomer. We want to isolate this oligomer using gold colloids because this step can be reversed. Utilizing gold colloids allows us to freeze fibrillogenesis in the first step by folding and unfolding the protein repeatedly through a series of pH changes from 4 or below to 10 or higher. At …

Twenty-Year Survival Following Lung Transplantation, John James Miggins, Ross M Reul, Spencer Barrett, Abbas Rana, Ahmed Alnajar, Jordan Dunson, Alexis Shafii, Puneet Garcha, John Goss, Gabriel Loor

Faculty, Staff and Students Publications

BACKGROUND: Lung transplantation median survival has seen improvements due to recognition of short-term survival factors but continues to trail behind other solid organs due to limited understanding of long-term survivorship. Given the creation of the United Network for Organ Sharing (UNOS) database in 1986, it was difficult to accrue data on long-term survivors until recently. This study characterizes factors impacting lung transplant survival beyond 20 years, conditional to 1-year survival.

METHODS: Lung transplant recipients listed in UNOS from 1987 to 2002 who survived to 1 post-transplant year were reviewed. Kaplan-Meier and adjusted Cox regression analyses were performed at 20 and …

Anesthetic Considerations For Cardiac Tamponade After Internal Jugular Central Line Placement During Trauma Resuscitation: A Case Report, Kevin M Chen, Jamal Hasoon, Anvinh Nguyen

Faculty, Staff and Students Publications

Numerous complications are associated with central venous catheters. Among them, cardiac tamponade is a rare but well-documented catastrophic complication. A 22-year-old healthy male presented with Code 1 trauma resulting from gunshot wounds in the abdomen. Upon examination, he was found to have a large pericardial fluid collection, a large right supraclavicular hematoma, and significant amount of bilateral pleural effusions secondary to extraluminal placement of the right internal jugular central line during resuscitation. After repairing the internal jugular injury and draining the pericardial fluid, the patient was transferred from the intensive care unit to the regular hospital floor. However, 15 days …

An Improved Reporter Identifies Ruxolitinib As A Potent And Cardioprotective Camkii Inhibitor, Oscar E Reyes Gaido, Nikoleta Pavlaki, Jonathan M Granger, Olurotimi O Mesubi, Bian Liu, Brian L Lin, Alan Long, David Walker, Joshua Mayourian, Kate L Schole, Chantelle E Terrillion, Lubika J Nkashama, Mohit M Hulsurkar, Lauren E Dorn, Kimberly M Ferrero, Richard L Huganir, Frank U Müller, Xander H T Wehrens, Jun O Liu, Elizabeth D Luczak, Vassilios J Bezzerides, Mark E Anderson

Faculty, Staff and Students Publications

Ca2+/calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits of CaMKII inhibition in numerous preclinical models of heart disease, translation of CaMKII antagonists into humans has been stymied by low potency, toxicity, and an enduring concern for adverse effects on cognition due to an established role of CaMKII in learning and memory. To address these challenges, we asked whether any clinically approved drugs, developed for other purposes, were potent CaMKII inhibitors. For this, we engineered an improved fluorescent reporter, CaMKAR (CaMKII activity reporter), which features superior sensitivity, kinetics, and …

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …

Metals And Metal Complexes In Diseases With A Focus On Covid-19: Facts And Opinions, Agnieszka Ścibior, Manuel Aureliano, Alvin A. Holder, Juan Llopis

Chemistry & Biochemistry Faculty Publications

In the present Special Issue on “Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions”, an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties. The Special Issue compiles data on the role of metals in COVID-19 and focuses on other illnesses and biological processes that affect metal metabolism. It consists of eight manuscripts, including five review articles and three original research papers (Figure …

Cardiac Pericytes Mediate The Remodeling Response To Myocardial Infarction, Pearl Quijada, Shuin Park, Peng Zhao, Kamal Ss Kolluri, David Wong, Kevin D Shih, Kai Fang, Arash Pezhouman, Lingjun Wang, Ali Daraei, Matthew D Tran, Elle M Rathbun, Kimberly N Burgos Villar, Maria L Garcia-Hernandez, Thanh Td Pham, Charles J Lowenstein, M Luisa Iruela-Arispe, S Thomas Carmichael, Eric M Small, Reza Ardehali

Faculty, Staff and Students Publications

Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4-expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Systemic Sclerosis Associated Interstitial Lung Disease: A Conceptual Framework For Subclinical, Clinical And Progressive Disease, David Roofeh, Kevin K Brown, Ella A Kazerooni, Donald Tashkin, Shervin Assassi, Fernando Martinez, Athol U Wells, Ganesh Raghu, Christopher P Denton, Lorinda Chung, Anna-Maria Hoffmann-Vold, Oliver Distler, Kerri A Johannson, Yannick Allanore, Eric L Matteson, Leticia Kawano-Dourado, John D Pauling, James R Seibold, Elizabeth R Volkmann, Simon L F Walsh, Chester V Oddis, Eric S White, Shaney L Barratt, Elana J Bernstein, Robyn T Domsic, Paul F Dellaripa, Richard Conway, Ivan Rosas, Nitin Bhatt, Vivien Hsu, Francesca Ingegnoli, Bashar Kahaleh, Puneet Garcha, Nishant Gupta, Surabhi Khanna, Peter Korsten, Celia Lin, Stephen C Mathai, Vibeke Strand, Tracy J Doyle, Virginia Steen, Donald F Zoz, Juan Ovalles-Bonilla, Ignasi Rodriguez-Pinto, Padmanabha D Shenoy, Andrew Lewandoski, Elizabeth Belloli, Alain Lescoat, Vivek Nagaraja, Wen Ye, Suiyuan Huang, Toby Maher, Dinesh Khanna

Faculty, Staff and Students Publications

OBJECTIVES: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD).

METHODS: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification.

RESULTS: Forty-four experts (53%) completed …

Effect Of Temperature On The Microbiome Of A Laboratory Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna Mitchell

Poster Presentations

Honors research poster.

Haemaphysalis longicornis is a species of tick native to eastern Asia, including eastern China, Japan, eastern Russia, and Korea. To date, it has invaded and has now established its existence in Australia, New Zealand, and several of the Pacific Islands. This species of tick has recently been introduced to the United States, having a confirmed sighting in November 2017 on a sheep farm in New Jersey and since establishing populations in 18 states along the east coast and Appalachia. Based on the existing locations of H. longicornis in its native regions, as well as in the United …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations and Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

A Potential Role Of Gsk-3beta In The Development Of Pain Post-Spinal Cord Injury, Emily Ernst

Undergraduate Theses

Chronic neuropathic pain is a very common consequence following spinal cord injury (SCI) and poses significant clinical challenge. Current treatments are largely ineffective and as a result, patients are often left with debilitating pain at and below the level of the spinal cord injury. After spinal injury, a cascade of events occurs within the nervous system. One important aspect of this cascade for investigation is the anatomical changes that occur post-SCI. There is evidence of maladaptive sprouting/growth in sensory nerve fibers that is thought to play a role in the development and amplification of pain signals. Sprouting of primary afferents …

The Effects Of Specialized Pro-Resolving Mediator Lipoxin A4 On Pseudomonas Aeruginosa Biofilms And Interactions With Monocytes, Julianne M. Thornton

Graduate School of Biomedical Sciences Theses and Dissertations

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen known as a major cause of hospital-acquired secondary infections, commonly causing chronic respiratory infections in immunocompromised individuals, especially those with cystic fibrosis, and often found in wound infections. P. aeruginosa uses the quorum sensing pathway to readily form protective biofilms, which reduce the efficacy of antibiotics and access by host immune cells to eradicate the pathogen. Specialized pro-resolving mediators (SPMs) are lipids endogenously produced by the host immune response to infection to aid in infection resolution. One SPM, Lipoxin A4 (LxA4), has been shown to be a robust quorum sensing inhibitor.

The …

Investigating The Antibacterial And Immunomodulatory Properties Of Lactobacillus Acidophilus Postbiotics, Rachael M. Wilson

Graduate School of Biomedical Sciences Theses and Dissertations

Probiotics are nonpathogenic microorganisms that have been extensively studied for their ability to prevent various infectious, gastrointestinal, and autoimmune diseases. The mechanisms underlying these probiotic effects have not been elucidated. However, we and other researchers have evidence suggesting that probiotic bacteria secrete metabolites that are antimicrobial and anti-inflammatory. As such, we developed a methodology to collect the secreted metabolites from a probiotic bacterium, Lactobacillus acidophilus, and tested this cell free filtrate (CFF) both in vitro and in vivo. Using this CFF, we have demonstrated that L. acidophilus secretes a molecule(s) that has specific bactericidal activity against the opportunistic pathogen, Pseudomonas …

Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights …

Turmeric-Associated Liver Injury: A Rare Case Of Drug-Induced Liver Injury, David N Smith, Prisca Pungwe, Lauren L Comer, Teminioluwa A Ajayi, Milena G Suarez

Faculty, Staff and Students Publications

Turmeric is popularly used as a naturopathic supplement associated with myriad benefits and has long been generally regarded as safe. However, increasing reports of turmeric-associated liver injury have emerged over recent years. This case presents a female patient without significant past medical history who presents with signs and symptoms of acute hepatitis after consuming a turmeric-containing tea. Her case adds to a growing body of evidence that dosage safety, manufacturing, and pharmacologic delivery practices for turmeric supplements should be investigated.

Genetic Determinants Involved In Acquisition Of Iron In The Opportunistic Pathogen Mycobacterium Abscessus, Manal F. Farhat

Dissertations, Theses, and Capstone Projects

The opportunistic pathogen Mycobacterium abscessus subsp. abscessus (Mab) has become an emerging public health threat due to the increasing number of Mab-associated chronic pulmonary disease cases. Infection cure rates are only 50% due to the complex resistance of Mab to most antimicrobial drugs and chemotherapy.

Deeper knowledge of Mab biology is needed to illuminate potential candidates for development of improved therapeutics against Mab infections. The ESX-3 type VII protein secretion system of Mab plays an important role in host inflammatory and pathological responses during infection.

In this study, we demonstrate a functional link between the ESX-3 secretion …