Cell and Developmental Biology Commons^™

Development Of Septic Polysynovitis And Uveitis In Foals Experimentally Infected With Rhodococcus Equi, Laura Huber, Steeve Giguère, Londa J. Berghaus, Amanda Hanafi, Sarah Vitosh-Sillman, Sarah L. Czerwinski

School of Veterinary and Biomedical Sciences: Faculty Publications

Rhodococcus equi is one of the most important causes of disease in foals. Infection is typically characterized by pyogranulomatous pneumonia although extrapulmonary infections occur occasionally. Uveitis and polysynovitis have been reported in foals naturally infected with R. equi and are thought to be the result of an immune-mediated process. However, the pathogenesis of these conditions is poorly understood. The objectives of this study were to document the occurrence of uveitis and polysynovitis after experimental infection with R. equi and to determine if these disorders are the direct result of infection at these sites. Foals between 3 and 4 weeks of …

Alkaline Stabilization Of Manure Slurry Inactivates Porcine Epidemic Diarrhea Virus, Erin E. Stevens, Daniel N. Miller, Bethany A. Brittenham, Sarah J. Vitosh-Sillman, Bruce W. Brodersen, Virginia L. Jin, John D. Loy, Amy M. Schmidt

School of Veterinary and Biomedical Sciences: Faculty Publications

Hydrated lime manure treatment was evaluated to determine porcine epidemic diarrhea virus (PEDV) susceptibility to alkaline stabilization. At pH 10, PEDV decreased (quantitative polymerase chain reaction) and lost infectivity (swine bioassay). Although ammonium decreased above pH 9 (up to 25%), alkaline stabilization managed to control potential infection from manure sources.

Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry Identification Of Moraxella Bovoculi And Moraxella Bovis Isolates From Cattle, Kara Robbins, Aaron M. Dickey, Michael L. Clawson, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious bovine keratoconjunctivitis (IBK) is an economically significant disease caused by Moraxella bovis. Moraxella bovoculi, although not reported to cause IBK, has been isolated from the eyes of cattle diagnosed with IBK. Identification of M. bovis and M. bovoculi can be performed using biochemical or DNA-based approaches, both of which may be time consuming and inconsistent between laboratories. We conducted a comparative evaluation of M. bovoculi and M. bovis identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with a database provided by Bruker Daltonics (termed the BDAL database), the BDAL database supplemented with spectra generated in …

Circadian Behavioral Responses To Light And Optic Chiasm-Evoked Glutamatergic Epscs In The Suprachiasmatic Nucleus Of Iprgc Conditional Vglut2 Knock-Out Mice, Michael G. Moldavan, Patricia J. Sollars, Michael R. Lasarev, Charles N. Allen, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator that functions as a biological clock. ipRGCs use vesicular glutamate transporter 2 (vGlut2) to package glutamate into synaptic vesicles and light-evoked resetting of the SCN circadian clock is widely attributed to ipRGC glutamatergic neurotransmission. Pituitary adenylate cyclase-activating polypeptide (PACAP) is also packaged into vesicles in ipRGCs and PACAP may be coreleased with glutamate in the SCN. vGlut2 has been conditionally deleted in ipRGCs in mice [conditional knock-outs (cKOs)] and their aberrant photoentrainment and residual attenuated light responses have been ascribed to ipRGC PACAP release. However, …

Development Of A Multiplex Real-Time Pcr Assay Using Two Thermocycling Platforms For Detection Of Major Bacterial Pathogens Associated With Bovine Respiratory Disease Complex From Clinical Samples, John Dustin Loy, Laura Leger, Aspen M. Workman, Michael L. Clawson, Ece Bulut, Bing Wang

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine respiratory disease complex (BRDC) is one of the most significant diseases of cattle. Bacterial pathogens involved in BRDC include Mannheimia haemolytica, Mycoplasma bovis, Histophilus somni, and Pasteurella multocida. We developed and evaluated a multiplexed real-time hydrolysis probe (rtPCR) assay using block-based Peltier and rotary-based thermocycling on lung tissue, nasal swabs, and deep nasopharyngeal swabs. The rtPCR results were compared to culture or a gel-based M. bovis PCR using statistical analysis to determine optimum quantification cycle (Cq) cutoffs to maximize agreement. The limits of detection were 1.2–12 CFU/reaction for each pathogen. M. haemolytica was the most prevalent organism detected …

Coordinated Regulation Of Transcription By Ccpa And The Staphylococcus Aureus Twocomponent System Hptrs, Joseph M. Reed, Sean Olson, Danielle F. Brees, Caitlin E. Griffin, Ryan A. Grove, Paul J. Davis, Stephen D. Kachman, Jiri Adamec, Greg A. Somerville

School of Veterinary and Biomedical Sciences: Faculty Publications

The success of Staphylococcus aureus as a pathogen is due in part to its ability to adapt to changing environmental conditions using signal transduction pathways, such as metaboliteresponsive regulators and two-component systems. S. aureus has a two-component system encoded by the gene pair sav0224 (hptS) and sav0223 (hptR) that regulate the hexose phosphate transport (uhpT) system in response to extracellular glucose-6-phosphate. Glycolytic intermediates such as glucose-6-phosphate are important carbon sources that also modulate the activity of the global metabolite-responsive transcriptional regulator CcpA. Because uhpT has a putative CcpA binding site in its promoter and …

Novel Docosahexaenoic Acid Ester Of Phloridzin Inhibits Proliferation And Triggers Apoptosis In An In Vitro Model Of Skin Cancer, Theodora Mantso, Dimitrios T. Trafalis, Sotiris Botaitis, Rodrigo Franco, Aglaia Pappa, H. P. Vasantha Rupasinghe, Mihalis I. Panayiotidis

School of Veterinary and Biomedical Sciences: Faculty Publications

Skin cancer is among the most common cancer types accompanied by rapidly increasing incidence rates, thus making the development of more efficient therapeutic approaches a necessity. Recent studies have revealed the potential role of decosahexaenoic acid ester of phloridzin (PZDHA) in suppressing proliferation of liver, breast, and blood cancer cell lines. In the present study, we investigated the cytotoxic potential of PZDHA in an in vitro model of skin cancer consisting of melanoma (A375), epidermoid carcinoma (A431), and non-tumorigenic (HaCaT) cell lines. Decosahexaenoic acid ester of phloridzin led to increased cytotoxicity in all cell lines as revealed by cell viability …

Whole Genome Sequencing Of Moraxella Bovoculi Reveals High Genetic Diversity And Evidence For Interspecies Recombination At Multiple Loci, Aaron M. Dickey, Gennie Schuller, John D. Loy, Michael L. Clawson

School of Veterinary and Biomedical Sciences: Faculty Publications

Moraxella bovoculi is frequently cultured from the ocular secretions and conjunctiva of cattle with Infectious Bovine Keratoconjunctivitis (IBK). Previous work has shown that single nucleotide polymorphism (SNP) diversity in this species is quite high with 81,284 SNPs identified in eight genomes representing two distinct genotypes isolated from IBK affected eyes (genotype 1) and the nasopharynx of cattle without clinical IBK signs (genotype 2), respectively. The goals of this study were to identify SNPs from a collection of geographically diverse and epidemiologically unlinked M. bovoculi strains from the eyes of IBK positive cattle (n = 183) and another from the eyes …

Differential Modulation Of Human Gabac‑Ρ1 Receptor By Sulfur‑Containing Compounds Structurally Related To Taurine, Lenin David Ochoa‑De La Paz, Martin González‑Andrade, Herminia Pasantes‑Morales, Rodrigo Franco, Rubén Zamora‑Alvarado, Edgar Zenteno, Hugo Quiroz‑Mercado, Roberto Gonzales‑Salinas, Rosario Gulias‑Cañizo

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: The amino acid taurine (2-Aminoethanesulfonic acid) modulates inhibitory neurotransmitter receptors. This study aimed to determine if the dual action of taurine on GABAC- ρ1R relates to its structure. To address this, we tested the ability of the structurally related compounds homotaurine, hypotaurine, and isethionic acid to modulate GABAC- ρ1R.

Results: In Xenopus laevis oocytes, hypotaurine and homotaurine partially activate heterologously expressed GABAC- ρ1R, showing an increment in its deactivation time with no changes in channel permeability, whereas isethionic acid showed no effect. Competitive assays suggest that hypotaurine and homotaurine compete for the GABA-binding site. In addition, their effects were …

Using Art And Story To Explore How Primary School Students In Rural Tanzania Understand Planetary Health: A Qualitative Analysis, Elizabeth Vanwormer, Jesca Mlawa, Elizabeth Komba, Christopher Gustafson, Hilda Mrema, Jenny M. Dauer

School of Veterinary and Biomedical Sciences: Faculty Publications

Background The global planetary health community increasingly recognises the need to prepare students to investigate and address connections between environmental change and human health. As we strive to support education on planetary health themes for students of all ages, understanding students’ concepts of linkages between the health of people and animals, and their shared environments might advance educational approaches. Children living in villages bordering Ruaha National Park in Iringa Region, Tanzania, have direct experience of these connections as they share a water-stressed but biodiverse environment with domestic animals and wildlife. Livelihoods in these villages depend predominantly on crop and livestock …

Tellurite Resistance In Shiga Toxin-Producing Escherichia Coli , Gentry L. Lewis, Quentin R. Jorgensen, John Dustin Loy, Rodney A. Moxley

School of Veterinary and Biomedical Sciences: Faculty Publications

Potassium tellurite ( K₂TeO₃) is an effective selective agent for O157:H7 Shiga toxin-producing Escherichia coli (STEC), whereas tellurite resistance in non-O157 STEC is variable with information on O45 minimal. High-level K₂TeO₃ resistance in STEC is attributable to the ter gene cluster with terD an indicator of the cluster’s presence. Polymerase chain reactions for terD and K₂TeO₃ minimum inhibitory concentration (MIC) determinations in broth cultures were conducted on 70 STEC and 40 non-STEC control organisms. Sixty-six STEC strains (94.3%) were terD+ compared to 28 control organisms (70.0%; P < 0.001). The prevalence of terD in …

Epitope Mapping Of Serca2a Identifies An Antigenic Determinant That Induces Mainly Atrial Myocarditis In A/J Mice, Bharathi Krishnan, Chandirasegara Massilamany, Rakesh H. Basavalingappa, Arunakumar Gangaplara, Rajkumar Rajasekaran, Muhammad Z. Afzal, Vahid Khalilzad-Sharghi, You Zhou, Jean-Jack Riethoven, Shyam S. Nandi, Paras K. Mishra, Raymond A. Sobel, Jennifer L. Strande, David Steffen, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Sarcoplasmic/endoplasmic reticulum Ca²⁺ adenosine triphosphatase (SERCA)2a, a critical regulator of calcium homeostasis, is known to be decreased in heart failure. Patients with myocarditis or dilated cardiomyopathy develop autoantibodies to SERCA2a suggesting that they may have pathogenetic significance. In this report, we describe epitope mapping analysis of SERCA2a in A/J mice that leads us to make five observations: 1) SERCA2a contains multiple T cell epitopes that induce varying degrees of myocarditis. One epitope, SERCA2a 971–990, induces widespread atrial inflammation without affecting noncardiac tissues; the cardiac abnormalities could be noninvasively captured by echocardiography, electrocardiography, and magnetic resonance microscopy imaging. 2) SERCA2a …

Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, Mohammed Hoque

Dissertations and Theses

The thymus serves as the primary lymphoid organ responsible for the development and selection of a self-tolerant T cell repertoire. In paradox to its critical functions for the adaptive immune response, the thymus undergoes a profound age associated decline beginning in early adult life resulting in significant decline in T-cell function.Thymic epithelial cells (TECs) are the most critical component of the thymic microenvironment and undergo rapid turn-over, so understanding the cellular mechanisms responsible for the maintenance of TEC number and organization will be critical in counteracting age associated involution, particularly in cancer patients, due to enhanced degeneration in response to …

Charecterization Of The Innate Immune Response In The Rat Intervertebral Disc At The Tissue And Cellular Level, Matthew Guerreiro

Theses and Dissertations (Comprehensive)

Low back pain (LBP) affects up to 80% of the global population at some point during their life. The costs associated with LBP are estimated at $100 billion per year, putting significant strains on our healthcare system. As intervertebral disc (IVD) herniation is one of the major causes of LBP we decided to focus on herniation facilitated inflammatory responses, where damage caused by herniation triggers an innate immune response which likely results in pain, inflammation, and recruitment of specialized innate immune cells like macrophages to the affected area. Since the role of the inflammatory response is relatively uncharacterized in the …

The Pul37 Tegument Protein Guides Alphaherpesvirus Retrograde Axonal Transport To Promote Neuroinvasion, Alexsia L. Richards, Patricia J. Sollars, Jared D. Pitts, Austin M. Stults, Ekaterina E. Heldwein, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination of infection to sensory and autonomic ganglia of the peripheral nervous system following an initial exposure at mucosal surfaces. The peripheral ganglia serve as the latent virus reservoir and the source of recurrent infections such as cold sores (herpes simplex virus type I) and shingles (varicella zoster virus). However, the means by which these viruses routinely invade the nervous system is not fully understood. We report that an internal virion component, the pUL37 tegument protein, has a surface region that is an essential neuroinvasion effector. Mutation of this region rendered …

Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated And Defective In Neuroinvasion, Arun S. Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Ezhumalai Muthukrishnan, Sathish Kumar Natarajan, David Steffen, Hiep Vu, Gustavo Delho, Fernando Osorio, Thomas M. Petro, Shi-Hua Xiang, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted flavivirus responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, reemerged in the last decade causing serious human diseases, including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to the enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently lacking. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic; it is absent in many of the African isolates but present in all isolates from the recent …

Fluorescence-Reported Allelic Exchange Mutagenesis Reveals A Role For Chlamydia Trachomatis Tmea In Invasion That Is Independent Of Host Ahnak, M. J. Mckuen, Konrad E. Mueller, Y. S. Bae, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Development of approaches to genetically manipulate Chlamydia is fostering important advances in understanding pathogenesis. Fluorescence-reported allelic exchange mutagenesis (FRAEM) now enables the complete deletion of specific genes in C. trachomatis L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to ct694-ctl0063 translocated membrane-associated effector A (TmeA). Deletion of tmeA did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity …

Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated And Defective In Neuroinvasion, Arun Saravanakumar Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Ezhumalai Muthukrishnan, Sathish Kumar Natarajan, David Steffen, Hiep Vu, Gustavo A. Delhon, Fernando Osorio, Thomas M. Petro, Shi-Hua Xiang, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

ABSTRACT Zika virus (ZIKV), a mosquito-transmitted flavivirus responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, reemerged in the last decade causing serious human diseases, including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to the enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently lacking. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic; it is absent in many of the African isolates but present in all isolates from the …

Effectiveness Of Composting As A Biosecure Disposal Method For Porcine Epidemic Diarrhea Virus (Pedv)-Infected Pig Carcasses, Sarah Vitosh-Sillman, John Dustin Loy, Bruce Brodersen, Clayton Kelling, Kent M. Eskridge, Amy Millmier Schmidt

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine epidemic diarrhea virus (PEDV) is an enteric disease of swine that has emerged as a worldwide threat to swine herd health and production. Substantial research has been conducted to assess viability of the virus on surfaces of vehicles and equipment, in feed and water, and on production building surfaces, but little is known about the persistence in PEDV-infected carcasses and effective disposal methods thereof. This study was conducted to quantify the persistence of PEDV RNA via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) at various time-temperature combinations and in infected piglet carcasses subjected to composting. Although this method …

Cd80 Expressed By Cd8+ T Cells Contributes To Pd-L1-Induced Apoptosis Of Activated Cd8+ T Cells, Meagan R. Rollins, Rachel M. Gibbons Johnson

Biology Publications

Tumor cells are capable of limiting antitumor CD8+ T cell responses through their cell surface expression of PD-L1. In addition to PD-1 expressed by CD8+ T cells, PD-L1 also binds to CD80 expressed by CD8+ T cells. The influence of the PD-L1/CD80 interaction on CD8+ T cell function has not been fully characterized, so we sought to investigate the impact of the PD-L1/CD80 interaction on PD-L1-induced apoptosis of activated CD8+ T cells. We found that CD8+ T cells that lacked CD80 expression got activated to the same extent as wild-type CD8+ T cells, but when cultured with anti-CD3 and PD-L1/Fc …

The Trophic Life Cycle Stage Of The Opportunistic Fungal Pathogen Pneumocystis Murina Hinders The Ability Of Dendritic Cells To Stimulate Cd4+ T Cell Responses, Heather M. Evans, Andrew Simpson, Shu Shen, Arnold J. Stromberg, Carol L. Pickett, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The life cycle of the opportunistic fungal pathogen Pneumocystis murina consists of a trophic stage and an ascus-like cystic stage. Infection with the cyst stage induces proinflammatory immune responses, while trophic forms suppress the cytokine response to multiple pathogen-associated molecular patterns (PAMPs), including β-glucan. A targeted gene expression assay was used to evaluate the dendritic cell response following stimulation with trophic forms alone, with a normal mixture of trophic forms and cysts, or with β-glucan. We demonstrate that stimulation with trophic forms downregulated the expression of multiple genes normally associated with the response to infection, including genes encoding …

Evaluation Of The Effect Of Serum Antibody Abundance Against Bovine Coronavirus On Bovine Coronavirus Shedding And Risk Of Respiratory Tract Disease In Beef Calves From Birth Through The First Five Weeks In A Feedlot, Aspen M. Workman, Larry A. Kuehn, Tara G. Mcdaneld, Michael L. Clawson, Carol G. Chitko-Mckown, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Objective: To evaluate the effect of serum antibody abundance against bovine coronavirus (BCV) on BCV shedding and risk of bovine respiratory disease (BRD) in beef calves from birth through the first 5 weeks in a feedlot.

Animals: 890 natural-service crossbred beef calves from 4 research herds.

Procedures: Serial blood samples for measurement of serum anti-BCV antibody abundance by an ELISA and nasal swab specimens for detection of BCV and other viral and bacterial BRD pathogens by real-time PCR methods were collected from all calves or subsets of calves at predetermined times from birth through the first 5 weeks after feedlot …

Study Of Regulated Cell Death In Two Systems: Pd-1 In Natural Killer Cells And Rip3 In Neurons, Yu Huang

Dissertations and Theses (Open Access)

Cell death is not only an essential phenomenon in normal development and homeostasis, but also crucial in various pathologies. It is now clear that many types of cell death can be regulated by pharmacological or genetic interventions. These were largely achieved by identifying the molecular mechanisms underlying the regulated cell death (RCD). While in the immune system, RCD needs to be facilitated to help the clearance of pathogens and tumors, in healthy cells, especially the terminally differentiated neurons in the nervous system, it is more desirable to protect cells from dying due to stress under pathological conditions. Thus, understating the …

More Haste, Less Speed: Could Public-Private Partnerships Advance Cellular Immunotherapies?, Tania M. Bubela, Katherine Bonter, Silvy Lachance, Jean-Sébastien Delisle, E Richard Gol

Office of the Provost

Cellular immunotherapies promise to transform cancer care. However, they must overcome serious challenges, including: (1) the need to identify and characterize novel cancer antigens to expand the range of therapeutic targets; (2) the need to develop strategies to minimize serious adverse events, such as cytokine release syndrome and treatment-related toxicities; and (3) the need to develop efficient production/manufacturing processes to reduce costs. Here, we discuss whether these challenges might better be addressed through forms of public-private research collaborations, including public-private partnerships (PPPs), or whether these challenges are best addressed by way of standard market transactions. We reviewed 14 public-private relationships …

A Parapoxviral Virion Protein Inhibits Nf-Κb Signaling Early In Infection, Sushil Khatiwada, Gustavo A. Delhon, Ponnuraj Nagendraprabhu, Sabal Chaulagain, Shuhong Luo, Diego G. Diel, Eduardo F. Flores, D. L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virusinfected cells (30 min post infection). Expression of ORFV073 alone was sufficient to …

Cross Reactivity Of Immune Responses To Porcine Reproductive And Respiratory Syndrome Virus Infection, Ignacio Correas, Fernando A. Osorio, David Steffen, Asit K. Pattnaik, Hiep L. X. Vu

School of Veterinary and Biomedical Sciences: Faculty Publications

Because porcine reproductive and respiratory syndrome virus (PRRSV) exhibits extensive genetic variation among field isolates, characterizing the extent of cross reactivity of immune responses, and most importantly cell-mediated immunity (CMI), could help in the development of broadly cross-protective vaccines. We infected 12 PRRSV-naïve pigs with PRRSV strain FL12 and determined the number of interferon (IFN)-γ secreting cells (SC) by ELISpot assay using ten type 2 and one type 1 PRRSV isolates as recall antigens. The number of IFN-γ SC was extremely variable among animals, and with exceptions, late to appear. Cross reactivity of IFN-γ SC among type 2 isolates was …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Stromal Fibroblasts Restrain The Rate Of Colon Cancer Progression And Metastasis By Suppressing Regulatory T Cells And Colon Cancer Stem Cells, Changsoo Kwak

Dissertations and Theses (Open Access)

The initiation, progression, and metastasis of tumors involve not only cancer cells, but also the tumor microenvironment, which consists of immune or inflammatory cells, fibroblasts, endothelial cells, and extracellular matrix components (ECM). Fibroblasts are ubiquitous stromal cells that can influence other neighboring cell types through the secretion of chemokines, cytokines, ECM, ECM remodeling enzymes, and other metabolites. Myofibroblasts are a distinct subtype of fibroblasts characterized by expression α-smooth muscle actin (αSMA). These cells are a dominant component of the microenvironment, and a FSP1 and FAP could be a different clone of fibroblasts. Myofibroblasts also have been known to contribute to …

The Five Immune Forces Impacting Dna-Based Cancer Immunotherapeutic Strategy, Suneetha Amara, Venkataswarup Tiriveedhi

Biology Faculty Research

DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success. Several options are currently under various stages of study to overcome immune inhibitory effect in tumor microenvironment. Some of these approaches include, but are not limited to, …

P23. Elucidation Of The Signaling Pathway Of Mertk, Kyle Taruc

Western Research Forum

Background

Mer Tyrosine Kinase (MERTK) is a receptor which mediates efferocytosis – removal of apoptotic cells by phagocytes such as macrophages. MERTK plays a critical role in homeostasis, with mutations in MERTK associated with the development and progression of atherosclerosis, the buildup of cholesterol-laden plaque in the sub-arterial space. Indeed, one MERTK allele is associated with 66% (heterozygous) to 75% (homozygous) protection from atherosclerosis, while other alleles and SNP’s pre-dispose to atherosclerosis and autoimmunity. Complications resulting from atherosclerosis, including heart attack and stroke, are currently the second leading cause of mortality in Canada. Despite the importance of MERTK in atherosclerosis …