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Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater 2018 University of Louisville

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study ...


31 - The Critical Role Of Atad3a In The Estrogen Signaling Pathway In Breast Cancer Cells, Parth Thakkar 2018 Augusta University

31 - The Critical Role Of Atad3a In The Estrogen Signaling Pathway In Breast Cancer Cells, Parth Thakkar

Georgia Undergraduate Research Conference (GURC)

Abstract

Breast cancer is the leading malignancy and leading cause of cancer-related death in women globally. The greatest barrier to a treatment is the incomplete understanding of mechanisms underlying molecular regulators whose function is cellular adaptation to estrogen. One such enzyme, ATAD3A, a nuclear-encoded mitochondrial enzyme, has been brought under this lab’s scrutiny. The role of ATAD3A in breast cancer progression is largely unknown but it has been shown to be a crucial mediator in promoting cell cycle progression. The two objectives of this project were: to determine whether the ATAd3A is an Estrogen Receptor-α target (ERα) and to ...


21 - Cigarette Smoke Exposure Upregulation Of Pge₂ Expression In The Bladder, Jessica Nix 2018 University of North Georgia

21 - Cigarette Smoke Exposure Upregulation Of Pge₂ Expression In The Bladder, Jessica Nix

Georgia Undergraduate Research Conference (GURC)

CIGARETTE SMOKE EXPOSURE UPREGULATION OF PGE₂ EXPRESSION IN THE BLADDER

Jessica Nix, Jane McHowat, Shannon Kispert

Cigarette smoking remains the leading cause of preventable death and disease in the United States. Despite known risks, 42.1 million Americans continue to smoke, making research into tobacco-related pathologies relevant and necessary. We previously discovered that cigarette smoke exposure leads to tumor progression in the breast via platelet activating factor (PAF) and other phospholipase A₂ (PLA₂) metabolic pathways. These results led us to examine the PLA2 metabolite, prostaglandin E₂ (PGE₂). We observed the expression of PGE₂ in mouse bladder and human heart ...


Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay 2018 Selected Works

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

David Turay, MD

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It ...


The Conquest Of Pus -- A History Of Bitumen, Creosote And Carbolic Acid, Charles T. Ambrose 2018 University of Kentucky

The Conquest Of Pus -- A History Of Bitumen, Creosote And Carbolic Acid, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

In the Western world from antiquity on, open wounds were treated topically with petroleum-derived substances, such as bitumen, asphalt, pitch, and tar. The immediate aim was to stifle bleeding and ease pain but a potential benefit was preventing local corruption with pus formation. In the early 19th century, creosote was recovered from bitumen and found to reduce suppuration. Carbolic acid was later isolated from creosote and recognized as an underlying active agent. In the 1860s, carbolic acid was first employed by Jules Lemaire to treat local skin infections and later by Joseph Lister to prevent the suppuration in compound fractures ...


Atherosclerosis In Subjects Newly Diagnosed With Human Immunodeficiency Virus Infection., Tatiana V Kirichenko, Veronika A Myasoedova, Tatiana E Shimonova, Alexandra A Melnichenko, Dmitri Sviridov, Igor A Sobenin, Alexey I Mazus, Alexander N Orekhov, Michael I Bukrinsky 2018 George Washington University

Atherosclerosis In Subjects Newly Diagnosed With Human Immunodeficiency Virus Infection., Tatiana V Kirichenko, Veronika A Myasoedova, Tatiana E Shimonova, Alexandra A Melnichenko, Dmitri Sviridov, Igor A Sobenin, Alexey I Mazus, Alexander N Orekhov, Michael I Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

HIV infection is associated with the increased risk of cardiovascular disease (CVD), even in patients successfully treated with the combination antiretroviral therapy (cART). However, the relationship between HIV, cART, and pathogenesis of CVD remains controversial. In the present study, we evaluated the carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis, in HIV-infected subjects receiving or not receiving cART. One hundred nine newly diagnosed HIV-infected subjects and one hundred nine uninfected age-matched controls (all males) without the history of CVD, hypertension, or diabetes were recruited into the present study. Cross-sectional analysis at baseline (BL) showed significantly increased levels of triglycerides ...


Cd4 T Cell Interaction With Intestinal Microbes Under Homeostasis And Inflammation, Jiani Chai 2018 Washington University in St. Louis

Cd4 T Cell Interaction With Intestinal Microbes Under Homeostasis And Inflammation, Jiani Chai

Arts & Sciences Electronic Theses and Dissertations

Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cells responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. Here, we addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg responses during homeostasis and Teff responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis. In fact, 4/6 Treg TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the ...


Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh 2018 Washington University in St. Louis

Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh

Arts & Sciences Electronic Theses and Dissertations

Protective immune responses to Mycobacterium tuberculosis (Mtb) must induce bactericidal functions while minimizing damage to the lung. Such responses require precise control of pro- and anti-inflammatory factors to regulate the recruitment and function of protective immune cells but the mechanisms by which this control is exerted remain incompletely defined. Basic helix-loop-helix family, member e40 (Bhlhe40) is a transcription factor known to regulate production of pro- and anti-inflammatory cytokines that affect protective immunity to Mtb. Immune-responsive Gene 1 (Irg1) is an enzyme that generates itaconate, a metabolite with potential anti-inflammatory and antibacterial roles during Mtb infection. The impact of Bhlhe40 and ...


Carnosol Modulates Th17 Cell Differentiation And Microglial Switch In Experimental Autoimmune Encephalomyelitis, Xing Li, Li Zhao, Juan-Juan Han, Fei Zhang, Shuai Liu, Lin Zhu, Zhe-Zhi Wang, Guang-Xian Zhang, Yuan Zhang 2018 Thomas Jefferson University; Shaanxi Normal University

Carnosol Modulates Th17 Cell Differentiation And Microglial Switch In Experimental Autoimmune Encephalomyelitis, Xing Li, Li Zhao, Juan-Juan Han, Fei Zhang, Shuai Liu, Lin Zhu, Zhe-Zhi Wang, Guang-Xian Zhang, Yuan Zhang

Department of Neurology Faculty Papers

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35–55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and ...


Endomembrane-Associated Pre-Embedding Immunogold Labeling, Zuzana Nichtova, Celia Fernandez-Sanz, A. Bartok, Sergio De La Fuente, György Hajnóczky, Shey-Shing Sheu, György Csordás 2018 Thomas Jefferson University

Endomembrane-Associated Pre-Embedding Immunogold Labeling, Zuzana Nichtova, Celia Fernandez-Sanz, A. Bartok, Sergio De La Fuente, György Hajnóczky, Shey-Shing Sheu, György Csordás

Department of Pathology, Anatomy, and Cell Biology Posters

Aim

To optimize the pre-embedding IG in stable cell lines and primary adult cardiomyocytes to get the most effective visualization of endomembrane/associated proteins: endo/sarcoplasmic reticulum Ca2+ release channels IP3 receptors and ryanodine receptors (IP3R, and RyR2) and the mitochondrial fission protein Drp1.


With Some Risk-Taking And Luck: A Veterinarian's Adventures In Viral Immunology., Luis J. Sigal 2018 Thomas Jefferson University

With Some Risk-Taking And Luck: A Veterinarian's Adventures In Viral Immunology., Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

No abstract provided.


Tgf-Β Sustains Tumor Progression Through Biochemical And Mechanical Signal Transduction., Robert L Furler, Douglas F Nixon, Christine A Brantner, Anastas Popratiloff, Christel H Uittenbogaart 2018 George Washington University

Tgf-Β Sustains Tumor Progression Through Biochemical And Mechanical Signal Transduction., Robert L Furler, Douglas F Nixon, Christine A Brantner, Anastas Popratiloff, Christel H Uittenbogaart

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Transforming growth factor β (TGF-β) signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD transcription factor signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix (ECM) remodeling. In this article, we review how TGF-β activated kinase 1 (TAK1) activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development is critical for designing therapeutics that ...


Characterizing The Role Of Fungal Shape In A Zebrafish Model Of Invasive Candidiasis, Brittany Seman 2018 University of Maine

Characterizing The Role Of Fungal Shape In A Zebrafish Model Of Invasive Candidiasis, Brittany Seman

Electronic Theses and Dissertations

Candida albicans is a common hospital-acquired fungal infection, and disseminated disease claims up to one-half of those afflicted. C. albicans has a unique ability to differentiate its shape during infection, and this differentiation is thought to be a major virulence factor during invasive infections. Each shape is proposed to have a specialized role: filaments drive tissue invasion and yeast mediate dissemination to the bloodstream. However, it has been difficult to test these hypotheses for two reasons. First, rigorous testing of shape-specific roles requires diverse strategies of shape modulation that restrict the possibility of manipulation-specific artifacts. Second, although connecting shape to ...


Avoiding Death Like The Plague: Wound Care In The Roman Army, Gwendolyn E. Dougherty 2018 Nazareth College of Rochester

Avoiding Death Like The Plague: Wound Care In The Roman Army, Gwendolyn E. Dougherty

#History: A Journal of Student Research

At its peak, Roman Empire controlled over two million square miles of territory. To conquer and control that much land, Rome produced a highly skilled army. Casualties and deaths were to be expected, but ancient medical sources about caring for the wounded in the Roman army point to treatments considered advanced for the time period. Galen of Pergamum was an important contributor to this field. The use of food products and natural resources helped combat infections, healing the wounded soldiers and returning them to their military units. This paper identifies and analyzes what those specific products for wound care were ...


Borrelia Burgdorferi Spovg Dna- And Rna-Binding Protein Modulates The Physiology Of The Lyme Disease Spirochete, Christina R. Savage, Brandon L. Jutras, Aaron Bestor, Kit Tilly, Patricia A. Rosa, Yvonne Tourand, Philip E. Stewart, Catherine A. Brissette, Brian Stevenson 2018 University of Kentucky

Borrelia Burgdorferi Spovg Dna- And Rna-Binding Protein Modulates The Physiology Of The Lyme Disease Spirochete, Christina R. Savage, Brandon L. Jutras, Aaron Bestor, Kit Tilly, Patricia A. Rosa, Yvonne Tourand, Philip E. Stewart, Catherine A. Brissette, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The SpoVG protein of Borrelia burgdorferi, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism ...


Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer 2018 Washington University in St. Louis

Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer

Arts & Sciences Electronic Theses and Dissertations

Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are ...


Samhd1 Phosphorylation Coordinates The Anti-Hiv-1 Response By Diverse Interferons And Tyrosine Kinase Inhibition., Matthew A Szaniawski, Adam M Spivak, James E Cox, Jonathan L Catrow, Timothy Hanley, Elizabeth S C P Williams, Michel J Tremblay, Alberto Bosque, Vicente Planelles 2018 George Washington University

Samhd1 Phosphorylation Coordinates The Anti-Hiv-1 Response By Diverse Interferons And Tyrosine Kinase Inhibition., Matthew A Szaniawski, Adam M Spivak, James E Cox, Jonathan L Catrow, Timothy Hanley, Elizabeth S C P Williams, Michel J Tremblay, Alberto Bosque, Vicente Planelles

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Macrophages are susceptible to human immunodeficiency virus type 1 (HIV-1) infection despite abundant expression of antiviral proteins. Perhaps the most important antiviral protein is the restriction factor sterile alpha motif domain and histidine/aspartic acid domain-containing protein 1 (SAMHD1). We investigated the role of SAMHD1 and its phospho-dependent regulation in the context of HIV-1 infection in primary human monocyte-derived macrophages and the ability of various interferons (IFNs) and pharmacologic agents to modulate SAMHD1. Here we show that stimulation by type I, type II, and to a lesser degree, type III interferons share activation of SAMHD1 via dephosphorylation at threonine-592 as ...


Negative Regulators Of Colonic Peripheral Regulatory T Cell Development, Teresa Lei Ai 2018 Washington University in St. Louis

Negative Regulators Of Colonic Peripheral Regulatory T Cell Development, Teresa Lei Ai

Arts & Sciences Electronic Theses and Dissertations

Peripheral Treg cells (pTreg cells) maintain immune homeostasis at mucosal interfaces, where they can develop upon activation of naïve CD4+ T cells by bacteria antigen. However, the cellular and molecular requirements that govern their differentiation in inflamed and homeostatic contexts require further elucidation. To circumvent uncertainties in existing methods of distinguishing pTreg cells from thymic Treg cells (tTreg cells), we analyzed monoclonal cell populations of CT2 and CT6 transgenic (Tg) cells that develop into pTreg cells in response to different species of endogenously presented Helicobacter antigen. In our comprehensive assessment of multiple intestinal inflammatory models, including infections and physical injury ...


Allatostatin C Modulates Nociception And Immunity In Drosophila., Nathaniel D Bachtel, Gary A Hovsepian, Douglas F Nixon, Ioannis Eleftherianos 2018 George Washington University

Allatostatin C Modulates Nociception And Immunity In Drosophila., Nathaniel D Bachtel, Gary A Hovsepian, Douglas F Nixon, Ioannis Eleftherianos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Bacterial induced inflammatory responses cause pain through direct activation of nociceptive neurons, and the ablation of these neurons leads to increased immune infiltration. In this study, we investigated nociceptive-immune interactions in Drosophila and the role these interactions play during pathogenic bacterial infection. After bacterial infection, we found robust upregulation of ligand-gated ion channels and allatostatin receptors involved in nociception, which potentially leads to hyperalgesia. We further found that Allatostatin-C Receptor 2 (AstC-R2) plays a crucial role in host survival during infection with the pathogenic bacterium Photorhabdus luminescens. Upon examination of immune signaling in AstC-R2 deficient mutants, we demonstrated that Allatostatin-C ...


Microrna Expression And Disease Correlation In A Hispanic Lupus Cohort, Thandiwe Jere 2018 University of Nebraska Medical Center

Microrna Expression And Disease Correlation In A Hispanic Lupus Cohort, Thandiwe Jere

Theses & Dissertations

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with varying clinical presentation and severity in different ethnicities/races. Micro-RNAs (miRNAs) modulate the immune system, and there is a growing interest in their role in SLE pathogenesis and disease presentation. Studies on miRNAs expression in SLE have been done in Caucasians and Asians but no comprehensive profiling has been done in Hispanics. This cross-sectional study of a Hispanic cohort of SLE patients (n =185) and healthy controls (HC) (n =185) from the Dominican Republic determined the expression of 10 selected miRNAs and their correlation to inflammatory markers and auto-antibody production ...


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