Biochemistry, Biophysics, and Structural Biology Commons^™

Altered Connexin 43 Expression Underlies Age-Dependent Decrease Of Regulatory T Cell Suppressor Function In Nonobese Diabetic Mice, Michel Kuczma, Cong-Yi Wang, Leszek Ignatowicz, Robert Gourdi, Piotr Kraj

Biological Sciences Faculty Publications

Type 1 diabetes is one of the most extensively studied autoimmune diseases, but the cellular and molecular mechanisms leading to T cell–mediated destruction of insulin-producing β cells are still not well understood. In this study, we show that regulatory T cells (T_regs) in NOD mice undergo age-dependent loss of suppressor functions exacerbated by the decreased ability of activated effector T cells to upregulate Foxp3 and generate T_regs in the peripheral organs. This age-dependent loss is associated with reduced intercellular communication mediated by gap junctions, which is caused by impaired upregulation and decreased expression of connexin 43. Regulatory …

Soy Isoflavones Mediate Radioprotection Of Normal Lung Tissue By Modulating The Radiation-Induced Inflammatory Response, Lisa Marie Abernathy

Wayne State University Dissertations

Radiation-induced lung injury (RILI) is caused by an early inflammatory process triggered by damage to lung parenchyma, epithelial cells, vascular endothelial cells and stroma. Initially, oxidative injuries after radiation induce altered expression of pro-inflammatory cytokines. Infiltrating inflammatory cells are stimulated and activated, producing additional mediators, resulting in a cytokine cascade. The expansion and perpetual activation of inflammatory cells, as well as lung parenchyma, lead to clinical pneumonitis. Activated cells produce molecular mediators and growth factors that affect the proliferation and gene expression of lung fibroblasts. This process leads to increased collagen synthesis and deposition, eventually leading to the development of …

Mutations In The 5’ Ntr And The Non-Structural Protein 3a Of The Coxsackievirus B3 Selectively Attenuate Myocarditogenicity, Chandirasegaran Massilamany, Arunakumar Gangaplara, Rakesh H. Basavalingappa, Rajkumar A. Rajasekaran, Hiep Vu, Jean-Jack Riethoven, David Steffen, Asit K. Pattnaik, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The 5’ non-translated region (NTR) is an important molecular determinant that controls replication and virulence of coxsackievirus B (CVB)3. Previous studies have reported many nucleotide (nt) sequence differences in the Nancy strain of the virus, including changes in the 5’ NTR with varying degrees of disease severity. In our studies of CVB3-induced myocarditis, we sought to generate an infectious clone of the virus for routine in vivo experimentation. By determining the viral nt sequence, we identified three new nt substitutions in the clone that differed from the parental virus strain: C97U in the 5’ NTR; a silent mutation, A4327G, in …

Confocal Fluorescence Microscopy: An Ultra-Sensitive Tool Used To Evaluate Intracellular Antiretroviral Nano-Drug Delivery In Hela Cells, Subhra Mandal, You Zhou, Annemarie Shibata, Christopher J. Destache

School of Veterinary and Biomedical Sciences: Faculty Publications

In the last decade, confocal fluorescence microscopy has emerged as an ultra-sensitive tool for real-time study of nanoparticles (NPs) fate at the cellular-level. According to WHO 2007 report, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the world’s major health threats by claiming approximately 7,000 new infections daily worldwide. Although combination antiretroviral drugs (cARV) therapy has improved the life-expectancy of HIV-infected patients, routine use of high doses of cARVhas serious health consequences and requires complete adherence to the regimen for success. Thus, our research goal is to fabricate long-acting novel cARV loaded poly(lactide-co-glycolic acid) (PLGA) nanoparticles (cARV-NPs) as …

Association Of Autophagy In The Cell Death Mediated By Dihydrotestosterone In Autoreactive T Cells Independent Of Antigenic Stimulation, Ting Jia, Annandurai Anandhan, Chandirasegaran Massilamany, Rajkumar A. Rajasekaran, Rodrigo Franco, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Gender disparity is well documented in the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139–151, in which female, but not male, SJL mice show a chronic relapsing-remitting paralysis. Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity of EAE, but the underlying mechanisms of its protective effects are unclear. Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151, we tested the hypothesis that DHT selectively modulates the expansion and functionalities of antigen-specific T cells. Unexpectedly, we noted that DHT induced cell death in antigen-specific, autoreactive T cells, but the effects were not …

Evaluation Of An Interactive Workshop Designed To Teach Practical Welfare Techniques To Beef Cattle Caretakers And Decision Makers, Reneé Dewell, Christy Hanthorn, Jared Danielson, Rebecca Burzette, Johann Coetzee, D. Dee Griffin, Alejandro Ramirez, Grant Dewell

School of Veterinary and Biomedical Sciences: Faculty Publications

The purpose of the project was to evaluate the use of an interactive workshop designed to teach novel practical welfare techniques to beef cattle caretakers and decision makers. Following training, respondents reported being more likely to use or recommend use of local anesthesia for dehorning and castration and were more inclined to use meloxicam for pain management. Respondents also reported improvement in performing all skills taught in the workshop. These results suggest instructional techniques used to teach practical concepts/techniques relevant to beef cattle welfare led to improvements in both perceived competency and estimated likelihood that the material will be used. …

Spiral Ganglion Degeneration And Hearing Loss As A Consequence Of Satellite Cell Death In Saposin B-Deficient Mice, Omar Akil, Ying Sun, Sarath Vijayakumar, Wujuan Zhang, Tiffany Ku, Chi-Kyou Lee, Sherri Jones, Gregory A. Grabowski, Lawrence R. Lustig

School of Veterinary and Biomedical Sciences: Faculty Publications

Saposin B (Sap B) is an essential activator protein for arylsulfatase A in the hydrolysis of sulfatide, a lipid component of myelin. To study Sap B’s role in hearing and balance, a Sap B-deficient (B^-/-) mouse was evaluated. At both light and electron microscopy (EM) levels, inclusion body accumulation was seen in satellite cells surrounding spiral ganglion (SG) neurons from postnatal month 1 onward, progressing into large vacuoles preceding satellite cell degeneration, and followed by SG degeneration. EM also revealed reduced or absent myelin sheaths in SG neurons from postnatal month 8 onwards. Hearing loss was initially seen …

Pseudorabies Virus Fast Axonal Transport Occurs By A Pus9- Independent Mechanism, Gina R. Daniel, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Reactivation from latency results in transmission of neurotropic herpesviruses from the nervous system to body surfaces, referred to as anterograde axonal trafficking. The virus-encoded protein pUS9 promotes axonal dissemination by sorting virus particles into axons, but whether it is also an effector of fast axonal transport within axons is unknown. To determine the role of pUS9 in anterograde trafficking, we analyzed the axonal transport of pseudorabies virus in the presence and absence of pUS9.

Haemorrhagic Colitis Associated With Enterohaemorrhagic Escherichia Coli O165:H25 Infection In A Yearling Feedlot Heifer, Rodney A. Moxley, Zachary R. Stromberg, Gentry L. Lewis, John D. Loy, Bruce W. Brodersen, Isha R. Patel, Jayanthi Gangiredla

School of Veterinary and Biomedical Sciences: Faculty Publications

Introduction: Enterohaemorrhagic Escherichia coli (EHEC) cause haemorrhagic colitis and haemolytic uraemic syndrome in humans. Although EHEC infection typically results in haemorrhagic colitis in all ages of human patients, in cattle it is usually limited to 1- to 5-week-old nursing calves.

Case Presentation: A 1-year-old feedlot beef heifer was moribund with neurological signs and bloody diarrhoea. At necropsy, the colonic mucosa contained multiple grossly visible haemorrhagic erosions, each measuring <1 mm in diameter. Histologically, foci corresponding to the gross erosions had E. coli O165 antigen-positive bacterial rods adherent to the apical surfaces of degenerate and necrotic colonic mucosal epithelial cells in association with attaching and effacing lesions, and also within cytoplasmic vacuoles in …

Characterization Of Newly Revealed Sequences In The Infectious Myonecrosis Virus Genome In Litopenaeus Vannamei, Duan S. Loy, Sijun Liu, Mark A. Mogler, J. Dustin Loy, Bradley J. Blitvich, Lyric C. Bartholomay

School of Veterinary and Biomedical Sciences: Faculty Publications

Infectious myonecrosis virus (IMNV) causes significant economic losses in farmed shrimp, where associated mortality in ponds can reach 70%. To explore host/pathogen interactions, a next-generation sequencing approach using lymphoid organ tissue from IMNV-infected Litopenaeus vannamei shrimp was conducted. Preliminary sequence assembly of just the virus showed that there were at least an additional 639 bp at the 5′ terminus and 23 nt at the 3′ terminus as compared with the original description of the IMNV genome (7561 nt). Northern blot and reverse transcription-PCR analysis confirmed the presence of novel sequence at both ends of the genome. Using 5′ RACE, an …

Mri-Compatible Bioreactors And Methods Of Using, Shadi Othman, Huihui Xu, Karin Wartella, Vahid Khalilzad-Sharghi, Ian Bargar

School of Veterinary and Biomedical Sciences: Faculty Publications

This disclosure describes a MRI-compatible bioreactor that allows a biological sample to be imaged in culture without disrupting or compromising the culture.

The Effect Of O Antigen Loss On The Protein Composition And Inflammatory Response Elicited By Klebsiella Pneumoniae, Bethaney Cahill

UNF Graduate Theses and Dissertations

Klebsiella pneumoniae is a Gram-negative pathogen associated with numerous infections. Like all Gram-negative bacteria, K. pneumoniae naturally release outer membrane vesicles (OMVs) during all stages of cellular growth. OMVs are composed of the outer membrane components such as lipopolysaccharide (LPS) and outer membrane proteins and contain cytosolic and periplasmic proteins in the lumen. K. pneumoniae is often found to lack an O antigen. The absence of the O antigen has been reported to alter the protein content of the membrane which may further alter the immune response elicited by K. pneumoniae. Therefore the purpose of this study was to …

Loss Of Thiol Repair Systems In Human Cataractous Lenses, Min Wei, Kui-Yi Xing, Yin-Chuan Fan, Teodosio Libondi, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. The purpose of this study was to investigate the thiol repair systems of thioltransferase (TTase) and thioredoxin (Trx) and oxidation-damaged proteins in human cataractous lenses.

METHODS. Cataractous lenses in humans (57–85 years of age) were classified into cortical, nuclear, mixed, mature, and hypermature cataract types by using a lens opacity classification system, and were obtained by extracapsular cataract extraction (ECCE) procedure. Cortical and nuclear cataracts were grouped by decreasing order of visual acuity into optical chart reading (R), counting fingers (CF), hand motion (HM), and light perception (LP). ECCE lens homogenate was analyzed for glutathione (GSH) level and enzyme …

Regulation Of C-Reactive Protein Gene Expression And Function, Avinash N. Thirumalai

Electronic Theses and Dissertations

Human C-reactive protein (CRP) is the prototypic acute phase protein whose serum concentration increases rapidly during inflammation. CRP is also associated with atherosclerosis; it is deposited at lesion sites where it may interact with modified lipoproteins. There are 2 major questions regarding CRP: 1. How is the serum concentration of CRP regulated? 2. What are the functions of CRP in atherosclerosis?

Our first aim was to determine the role of the constitutively expressed transcription factor Oct-1 in regulating CRP gene expression. We found that Oct-1 overexpression inhibited (IL-6+IL-1β)- induced CRP gene expression; maximal inhibition required the binding of Oct-1 to …

Glutaredoxin 2 (Grx2) Gene Deletion Induces Early Onset Of Age-Dependent Cataracts In Mice, Hongli Wu, Yibo Yu, Larry David, Ye-Shih Ho, Marjorie . F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and it controls thiol/ disulfide balance in cells. In this study, we investigated whether Grx2 gene deletion could induce faster age-related cataract formation and elucidated the biochemical changes effected by Grx2 gene deletion that may contribute to lens opacity. Slit lamp was used to examine the lenses in Grx2 knock-out (KO) mice and age-matched wild-type (WT) mice ages 1 to 16 months. In the Grx2 null mice, the lens nuclear opacity began at 5 months, 3 months sooner than …

The Pathological Effects Of Ccr2+ Inflammatory Monocytes Are Amplified By An Ifnar1-Triggered Chemokine Feedback Loop In Highly Pathogenic Influenza Infection, Sue-Jane Lin, Ming Lo, Rei-Lin Kuo, Shin-Ru Shih, David M. Ojcius, Jean Lu, Chien-Kuo Lee, Hui-Chen Chen, Meei Yun Lin, Chuen-Miin Leu, Chia-Ni Lin, Ching-Hwa Tsai

All Dugoni School of Dentistry Faculty Articles

Background: Highly pathogenic influenza viruses cause high levels of morbidity, including excessive infiltration of leukocytes into the lungs, high viral loads and a cytokine storm. However, the details of how these pathological features unfold in severe influenza infections remain unclear. Accumulation of Gr1 + CD11b + myeloid cells has been observed in highly pathogenic influenza infections but it is not clear how and why they accumulate in the severely inflamed lung. In this study, we selected this cell population as a target to investigate the extreme inflammatory response during severe influenza infection.

Results: We established H1N1 IAV-infected mouse models using …

A Novel Role For Nf-Κb In Proximal T Cell Signaling, Crystina Bronk Watson

USF Tampa Graduate Theses and Dissertations

The interrogation of T cell signaling over the past fifty years has led to the discovery of amazingly intricate cascade networks and elaborate descriptions of individual proteins' domains and functions. A complex landscape has been rendered in which proteins relay messages from the extracellular ligation of the TCR by a cognate peptide loaded MHC via changes in sub-cellular location, phosphorylation, and binding affinities and partners to enact nuclear localization of three key transcription factors required for cellular effector function and proliferation: AP-1, NF-AT, and NF-κB. Dogma has favored activation of each of these transcription regulating elements to be a linear …

Characterization Of Severe Fever With Thrombocytopenia Syndrome In Rural Regions Of Zhejiang, China, Lei Zhang, Ling Ye, David M. Ojcius, Xiuyu Lou, Chengwei Wang, Cen Feng, Yi Sun, Zhongfa Wang, Shibo Li, Yanjun Zhang

All Dugoni School of Dentistry Faculty Articles

Severe fever with thrombocytopenia syndrome virus (SFTSV) infections have recently been found in rural regions of Zhejiang. A severe fever with thrombocytopenia syndrome (SFTS) surveillance and sero-epidemiological investigation was conducted in the districts with outbreaks. During the study period of 2011–2014, a total of 51 SFTSV infection cases were identified and the case fatality rate was 12% (6/51). Ninety two percent of the patients (47/51) were over 50 years of age, and 63% (32/51) of laboratory confirmed cases occurred from May to July. Nine percent (11/120) of the serum samples from local healthy people without symptoms were found to be …

A Cytoplasmic Rna Virus Generates Functional Viral Small Rnas And Regulates Viral Ires Activity In Mammalian Cells, Kuo-Feng Weng, Chuan-Tien Hung, Po-Ting Hsieh, Mei-Ling L. Li, Guang-Wu Chen, Yu-An Kung, Peng-Nien Huang, Rei-Lin Kuo, Li-Lien Chen, Jing-Yi Lin, Robert Yung-Liang Wang, Shu-Jen Chen, Petrus Tang, Jim-Tong Horng, Hsing-I Huang, Jen-Ren Wang, David M. Ojcius, Gary Brewer, Shin-Ru Shih

All Dugoni School of Dentistry Faculty Articles

The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (>10⁵ copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced …

A Rational Framework For Evaluating The Next Generation Of Vaccines Against Mycobacterium Avium Subspecies Paratuberculosis, John P. Bannantine, Murray E. Hines Ii, Luiz E. Bermudez, Adel M. Talaat, Srinand Sreevatsan, Judith R. Stabel, Yung-Fu Chang, Paul M. Coussens, Raúl G. Barletta, William C. Davis, Desmond M. Collins, Yrjö T. Gröhn, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Since the early 1980s, several investigations have focused on developing a vaccine against Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease in cattle and sheep. These studies used whole-cell inactived vaccines that have proven useful in limiting disease progression, but have not prevented infection. In contrast, modified live vaccines that invoke a Th1 type immune response, may improve protection against infection. Spurred by recent advances in the ability to create defined knockouts in MAP, several independent laboratories have developed modified live vaccine candidates by transcriptional mutation of virulence and metablolic genes in MAP. In order to accelerate …

The Microtubule-Associated Protein, Eb1, Links Aim2 Inflammasomes With Autophagy-Dependent Secretion, Li-Jie Wang, Hsin-Yi Huang, Meng-Pin Huang, Willisa Liou, Ya-Ting Chang, Chih-Ching Wu, David M. Ojcius, Yu-Sun Chang

All Dugoni School of Dentistry Faculty Articles

Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 β (IL-1β) secretion. Numerous components involved in inflammasome activation have been identified, but the mechanisms of inflammasome-mediated IL-1β secretion have not yet been fully explored. Here, we demonstrate that end-binding protein 1 (EB1), which is required for activation of AIM2 inflammasome complex, links the AIM2 inflammasome to autophagy-dependent secretion. Imaging studies revealed that AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes. Biochemical analyses showed that poly(dA-dT)-activated AIM2 inflammasomes induce autophagy and IL-1β secretion in an LC3-dependent fashion. Furthermore, depletion of EB1 decreases autophagic shedding and intracellular trafficking. …

Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang

Dissertations

Embryonic stem cells (ESCs) have been recognized as a promising cell source for regenerative medicine. Intensive research over the past decade has led to the possibility that ESC-derived cells will be used for the treatment of human diseases. However, increasing evidence indicates that ESC-derived cells generated by the current differentiation methods are not fully functional. It is recently recognized that ESC-derived cells lack innate immunity to a wide range of infectious agents and inflammatory cytokines. When used in patients, ESC-derived cells would be placed in wounded sites that are exposed to various pathogens and inflammatory cytokines; therefore, their viability and …

Evaluation Of Eight Live Attenuated Vaccine Candidates For Protection Against Challenge With Virulent Mycobacterium Avium Subspecies Paratuberclosis In Mice, John Bannantine, Jamie L. Everman, Sasha J. J.Rose, Lmar Babrak, Robab Katani, Raul G. Barletta, Adel M. Talaat, Yrjö J. Gröhn, Yung-Fu Chang, Vivek Kapur, Luiz E. Bermudez

School of Veterinary and Biomedical Sciences: Faculty Publications

Johne's disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep, and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live vaccine for Johne's disease, we evaluated eight attenuated mutant strains of MAP using a C57BL/6 mouse model. The persistaence of the vaccine candidates was measured at 6, 12, and 18 weeks post vaccination. Only strains 320, 321, and 329 colonized both the liver and spleens up until the 12-week time point. The remaining five mutants …

Identification Of Cd24 As A Cancer Stem Cell Marker In Human Nasopharyngeal Carcinoma, Chun-Hung Yang, Hui-Ling Wang, Yi-Sheng Lin, K. P. Shravan Kumar, Hung-Chi Lin, Chih-Jung Chang, Chia-Chen Lu, Tsung-Teng Huang, Jan Martel, David M. Ojcius, Yu-Sun Chang, John Ding-E. Young, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24⁺ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/β-catenin signaling pathway. CD24⁺ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged …

Conformationally Stabilized Hiv Envelope Immunogens, Peter Kwong, John Mascola, Gary Nabel, Richard Wyatt, Barna Dey, Ling Xu, Tongqing Zhou, Joseph Sodroski, Wen Yuan, Shi-Hua Xiang

School of Veterinary and Biomedical Sciences: Faculty Publications

Isolated immunogens including a HIV-1 gp120 polypeptide or immunogenic fragment thereof stabilized in a CD4 bound confirmation by crosslinked cysteines, and methods of their use are disclosed. The immunogens are useful, for example, for generating an immune response to HIV-1 gp120 in a Subject.

Basal Nf-Κb Controls Il-7 Responsiveness Of Quiescent Naïve T Cells, Michelle L. Miller, Luqiu Chen, Ping Zhou, Xindong Liu, Monica Michelotti, Nicole Tramontini Gunn, Sarah E. Powers, Xiaoping Zhu, Cesar Evaristo, Maria-Luisa Alegre, Luciana L. Molinero

Biology Department Faculty Articles

T cells are essential for immune defenses against pathogens, such that viability of naïve T cells before antigen encounter is critical to preserve a polyclonal repertoire and prevent immunodeficiencies. The viability of naïve T cells before antigen recognition is ensured by IL-7, which drives expression of the prosurvival factor Bcl-2. Quiescent naïve T cells have low basal activity of the transcription factor NF-κB, which was assumed to have no functional consequences. In contrast to this postulate, our data show that basal nuclear NF-κB activity plays an important role in the transcription of IL-7 receptor α-subunit (CD127), enabling responsiveness of naïve …

Phthalates And Phthalate Alternatives: Effects On Proliferative And Estrogenic Target Genes In Ishikawa Cells, Ranjani Sundar '15, Ping Yin, Serdar E. Bulun

Student Publications & Research

Phthalates are used as plasticizers in many of the products found in medical, household, and industrial applications. Much research has not been completed on the effects of these phthalates as potential endocrine disrupting chemicals (EDCs). As these chemicals are ingested, the mechanism by which they affect the reproductive system is largely unknown. The purpose of this study was to observe how 2 phthalates, Di-n-butyl phthalate (DBP) and Diisononyl phthalate (DINP), and 2 phthalate alternatives, Dioctyl terephthalate (DOTP) and BHT (butylated hydroxytoluene)affect uterine cells in comparison to a vehicle treatment and 17β-Estradiol treatment. Changes in expression of mRNA were observed using …

The Effect Of Small Molecule 390 On Cxcr4 Receptors, Selam B. Zenebe-Gete '14, Shruti R. Topudurti '14, Shum Andrew, Richard J. Miller

Student Publications & Research

CXCR4 is the chemokine receptor which aids in chemotaxis of stem cells, such as those in the bone marrow or the brain. SDF-1 is the natural ligand for the CXCR4 receptor. Similarities between novel molecule 390 synthesized by the Miller Lab and SDF-1 make this novel small molecule a possible agonist of the CXCR4 receptor. To determine whether 390 is an agonist to the CXCR4 receptor, we transfected cells with CXCR4 and exposed them to no agonist [vehicle control], SDF-1, or varying concentrations of our agonist drug. Next, we took calcium images using the dye fura-2, which indicates changes in …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …