Immunology and Infectious Disease Commons^™

Concepts In Animal Parasitology, Chapter 29: Rhinebothriidea Healy Et Al., 2009 (Order) [Platyhelminthes, Cestoda, Eucestoda], Omar Lagunas-Calvo, Brenda Atziri García-García, Berenice Adán-Torres, Luis García-Prieto

Concepts in Animal Parasitology

An overview of the cestode (tapeworm) order Rhinebothriidea Healy et al., 2009, small worms that occur in the spiral intestine (valve) of rays (Batoidea) from marine and freshwater habitats worldwide. Includes discussion of their main morphological characteristics, a description and summary of a epresentative species, Anthocephalum currani Ruhnke and Seaman 2009, taxonomy, life cycle, and zoogeography.

Chapter 29 in Concepts in Animal Parasitology by Omar Lagunas-Calvo, Brenda Atziri García-García, Berenice Adán-Torres, and Luis García-Prieto. 2024. S. L. Gardner and S. A. Gardner, editors. Zea Books, Lincoln, Nebraska, United States. doi: 10.32873/unl.dc.ciap029

Distribution Of Tick Species On Free-Ranging Ungulates In Northern New England, Karisa Graham

Honors Theses and Capstones

In Northern New England, ungulates are often parasitized by ticks, which is one of the leading causes for the decline in population. Ungulates are a good host for ticks, specifically deer ticks and winter ticks, and these ticks cause many tick-borne diseases in humans as well. The purpose of this study was to assess passive sampling from harvested animals as a means of tick surveillance in Vermont and New Hampshire. Ticks were collected from deer and moose and mapped throughout the two states by ArcGIS to visualize the trends in distribution. Relative abundance was greater in southeastern Vermont, with no …

Innovations In Molecular Biomarkers And Biomaterial-Based Immunotherapies For Head & Neck Cancer, Sarah Anne Wong, Victoria A Manon, Simon Young, Chi T Viet

Faculty, Staff and Student Publications

Purpose of review: Oral squamous cell carcinoma (OSCC) survival rates have remained stagnant due to a lack of targeted therapies and diagnostic tools. Patient risk is currently determined solely through clinicopathologic features, primarily tumor staging, which lacks the necessary precision to stratify patients by risk and accurately dictate adjuvant treatment. Similarly, conventional OSCC therapies have well-established toxicities and limited efficacy.

Recent findings: Recent studies show that patient risk can now be assessed using non-invasive techniques, at earlier time points, and with greater accuracy using molecular biomarker panels. Additionally, novel immunotherapies not only utilize the host's immune response to combat disease …

The Immunobiology Of Myelodysplastic Neoplasms: A Mini-Review, Shruthi Kannan, Rolando A Vedia, Jeffrey J Molldrem

Faculty, Staff and Student Publications

This mini review summarizes the immunobiology of myelodysplastic syndromes, specifically focusing on the interactions between immune cells, cytokines, and dysplastic cells within the tumor microenvironment in the bone marrow. We elucidate in detail how immune dysregulation and evasion influence the initiation and progression of myelodysplastic syndromes, as well as resistance to therapy and progression to AML. In addition, we highlight a range of therapeutic strategies, including the most recent breakthroughs and experimental therapies for treating MDS. Finally, we address the existing knowledge gaps in the understanding of the immunobiology of MDS and propose future research directions, promising advancements toward enhancing …

Emerging Therapeutic Options For Follicular-Derived Thyroid Cancer In The Era Of Immunotherapy, Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C Henderson, Maria Puche, Sayan Alekseev, Jocelynn G Colunga-Minutti, Mark E Zafereo, Stephen Y Lai, Sang T Kim, Maria E Cabanillas, Roza Nurieva

Faculty, Staff and Student Publications

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also …

The Potential Of Stem Cell Therapy In Multiple Sclerosis Treatment: A Review, Sorina Amarculesei, Ava O'Meara Cushen, Cathy Brougham

SURE Journal: Science Undergraduate Research Experience Journal

Multiple Sclerosis is an autoimmune and neurodegenerative disease of the central nervous system. There are currently 2.8 million people living with Multiple Sclerosis worldwide, including 9000 people in Ireland, with a prevalence of 193 per 100,000 people. Symptoms of Multiple Sclerosis include sensory loss, fatigue, cognitive dysfunction, spasticity, depression, optic neuritis, gait ataxia, diplopia, and loss of bladder control. Currently, there is no standardised treatment or cure for Multiple Sclerosis with many strategies focusing on symptoms. Stem cells have emerged as promising approaches for Multiple Sclerosis therapeutics. Clinical trials primarily focus on mesenchymal stem cell-based therapies for Multiple Sclerosis. Furthermore, …

Treatment Response Of Gingival Squamous-Cell Carcinoma To Palliative Intent Immunotherapy, Natalia Trehan, Angelina Debbas, Mykaihla Sternick, Jennifer Johnson, James Gates

Department of Medical Oncology Faculty Papers

The use of PD-1 immune checkpoint inhibitor medications has become a common practice in the treatment of recurrent and metastatic head and neck squamous-cell carcinomas. Success in this setting has led to the investigation of their efficacy in locally advanced cases as a part of first-line therapy. In this report, we detail the treatment response to palliative intent immunotherapy of three geriatric patients with mandibular gingival squamous-cell carcinoma who decided against surgical intervention. Patient #1 was treated with pembrolizumab, a PD-1 inhibitor, and displayed complete clinical and radiologic response of the gingival mass after three months of treatment, which is …

Towards A Mode Of Action For The Anti-Schistosomal Aryl Hydantoins, Thomas Schulze

Theses & Dissertations

Schistosomiasis is a significant human disease caused by the helminth parasite Schistosoma mansoni. Praziquantel remains the only clinically used treatment, yet it is rapidly metabolized and only effective against the adult stage worm infection. Ro 13-3978 (AR02) is a potent antischistosomal compound with activity against multiple S. mansoni life stages; however, it manifests anti-androgenic activity. Additionally, the mechanism of action for worm clearance remains unknown. The structure of Ro 13-3979 was used to generate optimized derivatives, including AR102, that show increased potency towards worms, reduced off-target anti-androgen effects, and extended half-life thereby increasing the feasibility for a single-dose curative treatment. …

+Protective Roles For Interferon-Gamma In Astrocytes During Chronic Autoimmunity, Brandon C. Smith

ETD Archive

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS). Infiltrating inflammatory immune cells perpetuate demyelination and axonal damage in the CNS and significantly contribute to pathology and clinical deficits. Interferon (IFN)γ is classically described as deleterious in acute CNS autoimmunity, we and others have shown astrocytic IFNγ signaling also has a neuroprotective role. We found IFNγ signaling on astrocytes upregulates subunits of the immunoproteasome (iP) and programmed death ligand 1 (PD-L1), both of which serve protective roles during autoimmunity. Astrocyte-specific knockouts of Ifngr1 resulted in increased clinical severity in the MS murine model, experimental …

Intestinal Microbiome, Fecal Fermentation Profile, And Health Indices In Hiv Infected Men Versus Non-Infected Controls, Mary Andreae, Mary C. Andreae Mrs

Electronic Theses and Dissertations

Many HIV-positive (HIV+) males on Highly Active Anti-Retroviral Therapy (HAART) experience metabolic abnormalities, including Non-Alcoholic Fatty Liver Disease (NAFLD) and lipodystrophy. The intestinal microbiota and short chain fatty acids (SCFA), participate in bidirectional communication with their host. Dysbiosis in HIV+ males on HAART demonstrate a Prevotella-rich enterotype shaped by multiple factors including, medications, adiposity, diet, intestinal permeability, and lifestyle; our objective was to investigate these factors. 19 HIV+ and 21 HIV- males were enrolled. BMI and hip-to-waist ratio (H:W) were obtained, and FibroScan for liver health. Intestinal permeability markers Claudin-21, flagellin, and intestinal fatty acid binding protein (IFABP) in …

Human-Bat Interactions In A Disease Emergence Hotspot: Implications For Human Health And Bat Conservation, Reilly Tempest Jackson

Graduate Theses and Dissertations

Bats are an ecologically important taxon that can host zoonotic pathogens. Globally, many bat species are synanthropic and live closely with humans, often roosting in man-made structures. The spatial overlap between humans and bats creates opportunities for human-bat contact, which can lead to human exposure to bat-borne pathogens and conflicts that cause bat mortality. Despite this risk, little is known about the drivers and characteristics of these human-bat interactions in buildings and work is needed to understand this aspect of the wildlife-urban interface. In Chapter I, I present a literature review that identifies the geographic and taxonomic trends in reported …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Leucocytozoon Cariamae N. Sp. And Haemoproteus Pulcher Coinfection In Cariama Cristata (Aves: Cariamiformes): First Mitochondrial Genome Analysis And Morphological Description Of A Leucocytozoid In Brazil, Lis Marques De C. Vieira, Pedro Henrique O. Pereira, Daniel Ambrózio Da Rocha Vilela, Irène Landau, M. Andreína Pacheco, Ananias A. Escalante, Francisco C. Ferreira, Érika Martins Braga

Harold W. Manter Laboratory of Parasitology: Library Materials

The distribution of avian haemosporidians of the genus Leucocytozoon in the Neotropics remains poorly understood. Recent studies confirmed their presence in the region using molecular techniques alone, but evidence for gametocytes and data on putative competent hosts for Leucocytozoon are still lacking outside highland areas. We combined morphological and molecular data to characterize a new Leucocytozoon species infecting a non-migratory red-legged seriema (Cariama cristata), the first report of a competent host for Leucocytozoon in Brazil. Leucocytozoon cariamae n. sp. is distinguished from the Leucocytozoon fringillinarum group by its microgametocytes that are not strongly appressed to the host cell …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Mutation-Induced Changes In The Stability, B-Cell Epitope, And Antigenicity Of The Sars-Cov-2 Variant Spike Protein: A Comparative Computational Stud, Nira Meirita Wijayanti, Muhammad Hermawan Widyananda, Lailil Muflikhah, Nashi Widodo

Karbala International Journal of Modern Science

The spike (S) protein is a major antigenicity site that targets neutralizing antibodies and drugs. The growing number of S protein mutations has become a severe problem for developing effective vaccines. Here, we investigated four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that were the most infectious and widespread during the COVID-19 pandemic to determine the trends and patterns of mutation-induced changes in the stability, B-cell epitope, and antigenicity of the SARS-CoV-2 S protein. The data showed that the Beta and Gamma variants had three mutations on the receptor-binding domain (RBD), which is the specific site on the S …

Investigation Of Orthohantavirus Genetics In Rodent Reservoirs And Clinical Samples, Samuel Melvin Goodfellow

Biomedical Sciences ETDs

Orthohantaviruses are negative-sense, single stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of ~36% and the highest cases occuring in the southwest region. The primary SNV host reservoir is thought to be the western deer mouse, Peromyscus maniculatus, however it has been shown that other rodents can carry different orthohantaviruses. We designed a pan-orthohantavirus detection tool to survey several small mammal populations throughout New …

Investigating The Role Of Il-10 Producing Nkt Cells In Prevention Of Graft Versus Host Disease, Drew Boagni

Dissertations and Theses (Open Access)

The standard curative treatment for hematologic malignancies is allogeneic stem cell transplantation (ASCT), in which the patient’s immune system is replaced with that of a healthy donor. This can lead to cure through the graft versus leukemia (GVL) effect but can also cause graft versus host disease (GVHD), which is characterized by systemic inflammation and organ damage mediated by dysregulated donor T cells. Preclinical studies have shown invariant natural killer T cells (iNKT) cells can prevent GVHD while preserving GVL. iNKT cells are unconventional T cells which recognize glycolipid antigens presented in the context of CD1d. Upon activation, they secrete …

Nivolumab And Ipilimumab In Combination With Radiotherapy In Patients With High-Risk Locally Advanced Squamous Cell Carcinoma Of The Head And Neck., Jennifer Johnson, Ioannis A. Vathiotis, Larry Harshyne, Ayesha Ali, Voichita Bar-Ad, Rita S. Axelrod, Emily Lorber, Joseph Curry, David Cognetti, Adam J. Luginbuhl, Madalina Tuluc, Scott W Keith, M.G. Mahoney, Athanassios Argiris

Department of Medical Oncology Faculty Papers

BACKGROUND: The combination of nivolumab and ipilimumab has been approved for the treatment of multiple solid tumors. This was a phase I study investigating definitive radioimmunotherapy (RIT) with nivolumab and ipilimumab for the treatment of locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN).

METHODS: Patients with newly diagnosed, stage IVA-IVB SCCHN eligible for cisplatin-based chemotherapy received nivolumab (3 mg/kg every 2 weeks for a total of 17 doses) and ipilimumab (1 mg/kg every 6 weeks for a total of 6 doses) starting 2 weeks prior to radiotherapy. The primary endpoint was safety of definitive RIT. Secondary …

Preclinical Evaluation Of Anti-Cd38 Therapy In Mature T-Cell Neoplasms, Colleen Isabelle, William Johnson, Kathleen Mcconnell, Ashley Vogel, Jonathan Brammer, Amy Boles, Robyn Keller, Paola Sindaco, Liam Nisenfeld, Guldeep Uppal, Neda Nikbakht, Bruno Calabretta, Patrizia Porazzi, Jerald Gong, Nitin Chakravarti, Pierluigi Porcu, Anjali Mishra

Kimmel Cancer Center Faculty Papers

No abstract provided.

Tumor Biology And Immune Infiltration Define Primary Liver Cancer Subsets Linked To Overall Survival After Immunotherapy, Anuradha Budhu, Erica C Pehrsson, Aiwu He, Lipika Goyal, Robin Kate Kelley, Hien Dang, Changqing Xie, Cecilia Monge, Mayank Tandon, Lichun Ma, Mahler Revsine, Laura Kuhlman, Karen Zhang, Islam Baiev, Ryan Lamm, Keyur Patel, David E Kleiner, Stephen M Hewitt, Bao Tran, Jyoti Shetty, Xiaolin Wu, Yongmei Zhao, Tsai-Wei Shen, Sulbha Choudhari, Yuliya Kriga, Kris Ylaya, Andrew C Warner, Elijah F Edmondson, Marshonna Forgues, Tim F Greten, Xin Wei Wang

Kimmel Cancer Center Faculty Papers

Primary liver cancer is a rising cause of cancer deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces a potent response in a subset of patients, response rates vary among individuals. Predicting which patients will respond to immune checkpoint inhibitors is of great interest in the field. In a retrospective arm of the National Cancer Institute Cancers of the Liver: Accelerating Research of Immunotherapy by a Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples to profile the transcriptome and genomic alterations among 86 hepatocellular carcinoma and cholangiocarcinoma patients prior to and following immune checkpoint inhibitor treatment. …

Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).

In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …

Newer Surveillance Data Extends Our Understanding Of The Niche Of Rickettsia Montanensis (Rickettsiales: Rickettsiaceae) Infection Of The American Dog Tick (Acari: Ixodidae) In The United States, Catherine A. Lippi, Holly D. Gaff, Robyn M. Nadolny, Sadie J. Ryan

Biological Sciences Faculty Publications

Background: Understanding the geographic distribution of Rickettsia montanensis infections in Dermacentor variabilis is important for tick-borne disease management in the United States, as both a tick-borne agent of interest and a potential confounder in surveillance of other rickettsial diseases. Two previous studies modeled niche suitability for D. variabilis with and without R. montanensis, from 2002-2012, indicating that the D. variabilis niche overestimates the infected niche. This study updates these, adding data since 2012.

Methods: Newer surveillance and testing data were used to update Species Distribution Models (SDMs) of D. variabilis, and R. montanensis infected D. variabilis, in …

The Role Of Complement In Stroke And Traumatic Brain Injury, Christine Couch

MUSC Theses and Dissertations

Brain and neural injury are a non-specific disease category that includes traumatic brain injury (TBI) and stroke. Both TBI and stroke are common, costly, and leading causes of severe disability in adults. Both stroke and TBI are responsible for substantial disability in working age adults, with stroke being the second leading cause of death worldwide [1] and TBI a major cause of disability in people younger than their 40's [2]. The immune response after brain injury is multifactorial and involves both local and systemic events at the cellular and molecular level. The complement system is a component of both the …

Correction Of T-Cell Repertoire And Autoimmune Diabetes In Nod Mice By Non-Myeloablative T-Cell Depleted Allogeneic Hsct, Rakefet Sidlik Muskatel, Bar Nathansohn-Levi, Shlomit Reich-Zeliger, Michal Mark, Liat Stoler-Barak, Chava Rosen, Irit Milman-Krentsis, Esther Bachar Lustig, Robert Pete Gale, Nir Friedman, Yair Reisner

Faculty, Staff and Student Publications

The induction of partial tolerance toward pancreatic autoantigens in the treatment of type 1 diabetes mellitus (T1DM) can be attained by autologous hematopoietic stem cell transplantation (HSCT). However, most patients treated by autologous HSCT eventually relapse. Furthermore, allogeneic HSCT which could potentially provide a durable non-autoimmune T-cell receptor (TCR) repertoire is associated with a substantial risk for transplant-related mortality. We have previously demonstrated an effective approach for attaining engraftment without graft versus host disease (GVHD) of allogeneic T-cell depleted HSCT, following non-myeloablative conditioning, using donor-derived anti-3rd party central memory CD8 veto T cells (Tcm). In the present study, we investigated …

Investigating Host Cell Transcriptional Heterogeneity And Metabolism In Staphylococcus Aureus Biofilm Infections, Christopher M. Horn

Theses & Dissertations

Staphylococcus aureus (S. aureus) is a leading cause of prosthetic joint infection (PJI). These infections are often intractable due to biofilm formation, which are complex bacterial communities that adhere to biotic and abiotic surfaces. Within a biofilm, there is considerable heterogeneity in bacterial metabolism and gene expression that contributes to the establishment an anti-inflammatory milieu at the site of infection, which favors bacterial persistence even in the context of an immunocompetent host. This is due, in part, to the preferential recruitment of granulocytic myeloid-derived suppressor cells (G-MDSCs), which are a population of pathologically activated immature leukocytes that develop …

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 …

Prevalence Of Ehrlichia And Rickettsia Within Ticks In Arkansas State Parks, Haley Stanton

Animal Science Undergraduate Honors Theses

Within the past few decades, the number of diagnoses of tick-borne diseases – such as spotted fever rickettsiosis and ehrlichiosis – has steadily increased throughout the United States, with Arkansas having one of the highest rates in the country. These diseases pose a risk to both humans and animals, as both can acquire these infections from ticks. Due to the increasing geographic range of ticks, rise in cases, and likely underdiagnosis of these diseases, this study aimed to identify the infection rate of ticks themselves in multiple state parks in Arkansas. Four Arkansas state parks were each visited once a …

Investigating Novel Chemotherapeutics Against The Parasite Toxoplasma Gondii, Braydon Dreher

Theses/Capstones/Creative Projects

Toxoplasma gondii, an intracellular protozoan, is a globally prevalent parasite due to the infectivity of T. gondii with nearly 2.5 billion people affected worldwide. Toxoplasma gondii can cause toxoplasmosis, which is a disease acquired through the consumption of undercooked meat or found in the feces of felines, and often leads to profound neuropathology and potentially death. Currently, acute toxoplasmosis is treated with pyrimethamine and sulfadiazine, which is a combination of an antiprotozoal and a sulfonamide. This combination of drugs directly targets the acute stage of infection but has failed to eliminate or impact the chronic carriage of bradyzoites while …

The Cx3cl1-Cx3cr1 Chemokine Axis Contributes To Tumor Immune Evasion And Its Blockade Enhances Responses To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri

Dissertations and Theses (Open Access)

CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. While CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration, the mechanisms employed by this axis on these cells to mediate immune suppression remain poorly understood. Here, we explore the immune evasion strategies implemented by this axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of mediators to attract …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …