Molecular Genetics Commons^™

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage., Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John D'Orazio, D Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K St Clair, Luksana Chaiswing

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off-target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage by …

Project Give: Using A Virtual Genetics Service Platform To Reduce Health Inequities And Improve Access To Genomic Care In An Underserved Region Of Texas, Blake Vuocolo, Roberta Sierra, Daniel Brooks, Christopher Holder, Lauren Urbanski, Keila Rodriguez, Jose David Gamez, Surya Narayan Mulukutla, Ana Hernandez, Alberto Allegre, Humberto Hidalgo, Sarah Rodriguez, Sandy Magallan, Jeremy Gibson, Juan Carlos Bernini, Melanie Watson, Robert Nelson, Lizbeth Mellin-Sanchez, Nancy Garcia, Lori Berry, Hongzheng Dai, Claudia Soler-Alfonso, Kent Carter, Brendan Lee, Seema R Lalani

Faculty, Staff and Students Publications

BACKGROUND: The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley (RGV) at the Texas-Mexico border is predominantly Hispanic/Latino with a high poverty rate and very limited access to genetic services. Funded by the National Center for Advancing Translational Sciences, Project GIVE (Genetic Inclusion by Virtual Evaluation) was launched in 2022 to reduce the time to diagnosis and increase provider knowledge of genomics in this region, with the goal of …

Emerin Deficiency Drives Mcf7 Cells To An Invasive Phenotype, Emily Hansen, Christal Rolling, Matthew Wang, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer …

Rewiring The Sex-Determination Pathway During The Evolution Of Self-Fertility., Yongquan Shen, Shin-Yi Lin, Jonathan Harbin, Richa Amin, Allison Vassalotti, Joseph Romanowski, Emily Schmidt, Alexis Tierney, Ronald E Ellis

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show …

Genome-Wide Crispr Screen Reveals The Synthetic Lethality Between Bcl2l1 Inhibition And Radiotherapy, Ling Yin, Xiaoding Hu, Guangsheng Pei, Mengfan Tang, You Zhou, Huimin Zhang, Min Huang, Siting Li, Jie Zhang, Citu Citu, Zhongming Zhao, Bisrat G Debeb, Xu Feng, Junjie Chen

Faculty, Staff and Student Publications

Radiation therapy (RT) is one of the most commonly used anticancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part because of the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival after radiation. BCL2L1 …

Determining Effective Drug Concentrations For Selection And Counterselection Genetics In Drosophila Melanogaster, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick, Koen J T Venken

Faculty, Staff and Students Publications

We recently integrated into fly genetics a set of four selection and two counterselection markers and their corresponding drugs that can be used individually or in combination. These markers eliminate the need to visually screen progeny. Before using these markers in new genetic backgrounds, effective selection/counterselection concentrations should be established for each marker/drug combination. This protocol describes how to set up, perform, and analyze a drug titration curve to determine the effective selection/counterselection drug concentrations for their corresponding markers. For complete details on the use and execution of this protocol, please refer to Matinyan et al., 2021.

De Novo Frameshift Variants In The Neuronal Splicing Factor Nova2 Result In A Common C-Terminal Extension And Cause A Severe Form Of Neurodevelopmental Disorder, Francesca Mattioli, Gaelle Hayot, Nathalie Drouot, Bertrand Isidor, Jérémie Courraud, Maria-Victoria Hinckelmann, Frederic Tran Mau-Them, Chantal Sellier, Alica Goldman, Aida Telegrafi, Alicia Boughton, Candace Gamble, Sebastien Moutton, Angélique Quartier, Nolwenn Jean, Paul Van Ness, Sarah Grotto, Sophie Nambot, Ganka Douglas, Yue Cindy Si, Jamel Chelly, Zohra Shad, Elisabeth Kaplan, Richard Dineen, Christelle Golzio, Nicolas Charlet-Berguerand, Jean-Louis Mandel, Amélie Piton

Faculty, Staff and Students Publications

The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 …

The Zinc Transporter Zipt-7.1 Regulates Sperm Activation In Nematodes, Yanmei Zhao, Chieh-Hsiang Tan, Amber Krauchunas, Andrea Scharf, Nicholas Dietrich, Kurt Warnhoff, Zhiheng Yuan, Marina Druzhinina, Sam Guoping Gu, Long Miao, Andrew Singson, Ronald E Ellis, Kerry Kornfeld

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Sperm activation is a fascinating example of cell differentiation, in which immotile spermatids undergo a rapid and dramatic transition to become mature, motile sperm. Because the sperm nucleus is transcriptionally silent, this transition does not involve transcriptional changes. Although Caenorhabditis elegans is a leading model for studies of sperm activation, the mechanisms by which signaling pathways induce this transformation remain poorly characterized. Here we show that a conserved transmembrane zinc transporter, ZIPT-7.1, regulates the induction of sperm activation in Caenorhabditis nematodes. The zipt-7.1 mutant hermaphrodites cannot self-fertilize, and males reproduce poorly, because mutant spermatids are defective in responding to activating …

Zinc Transporters Ybtx And Znuabc Are Required For The Virulence Of Yersinia Pestis In Bubonic And Pneumonic Plague In Mice, Alexander G. Bobrov, Olga Kirillina, Marina Y. Fosso, Jacqueline D. Fetherston, M. Clarke Miller, Tiva T. Vancleave, Joseph A. Burlison, William K. Arnold, Matthew B. Lawrenz, Sylvie Garneau-Tsodikova, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A number of bacterial pathogens require the ZnuABC Zinc (Zn²⁺) transporter and/or a second Zn²⁺ transport system to overcome Zn²⁺ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn²⁺ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn²⁺ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic …

Borrelia Burgdorferi Reva Significantly Affects Pathogenicity And Host Response In The Mouse Model Of Lyme Disease, Rebecca Byram, Robert A. Gaultney, Angela M. Floden, Christopher Hellekson, Brandee L. Stone, Amy Bowman, Brian Stevenson, Barbara J. B. Johnson, Catherine A. Brissette

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, expresses RevA and numerous outer surface lipoproteins during mammalian infection. As an adhesin that promotes bacterial interaction with fibronectin, RevA is poised to interact with the extracellular matrix of the host. To further define the role(s) of RevA during mammalian infection, we created a mutant that is unable to produce RevA. The mutant was still infectious to mice, although it was significantly less well able to infect cardiac tissues. Complementation of the mutant with a wild-type revA gene restored heart infectivity to wild-type levels. Additionally, revA mutants led to increased evidence of arthritis, …

Intracellular Listeria Monocytogenes Comprises A Minimal But Vital Fraction Of The Intestinal Burden Following Foodborne Infection, Grant S. Jones, Kate M. Bussell, Tanya Myers-Morales, Abigail M. Fieldhouse, Elsa N. Bou Ghanem, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is a highly adaptive bacterium that replicates as a free-living saprophyte in the environment as well as a facultative intracellular pathogen that causes invasive foodborne infections. The intracellular life cycle of L. monocytogenes is considered to be its primary virulence determinant during mammalian infection; however, the proportion of L. monocytogenes that is intracellular in vivo has not been studied extensively. In this report, we demonstrate that the majority of wild-type (strain EGDe) and mouse-adapted (InlA^m-expressing) L. monocytogenes recovered from the mesenteric lymph nodes (MLN) was extracellular within the first few days after foodborne infection. In addition, …

Zhx2 Enhances The Cytotoxicity Of Chemotherapeutic Drugs In Liver Tumor Cells By Repressing Mdr1 Via Interfering With Nf-Ya, Hongxin Ma, Xuetian Yue, Lifen Gao, Xiaohong Liang, Wenjiang Yan, Zhenyu Zhang, Haixia Shan, Hualin Zhang, Brett T. Spear, Chunhong Ma

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated …

Anti-Cancer Activity Of Withaferin A In B-Cell Lymphoma., M K Mckenna, B W Gachuki, S S Alhakeem, K N Oben, V M Rangnekar, R C Gupta, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Withaferin A (WA), a withanolide from the plant, Ashwagandha (Withania somnifera) used in Ayurvedic medicine, has been found to be valuable in the treatment of several medical ailments. WA has been found to have anticancer activity against various solid tumors, but its effects on hematological malignancies have not been studied in detail. WA strongly inhibited the survival of several human and murine B cell lymphoma cell lines. Additionally, in vivo studies with syngeneic-graft lymphoma cells suggest that WA inhibits the growth of tumor but does not affect other proliferative tissues. We demonstrate that WA inhibits the efficiency of NF-κB nuclear …

Caspase-3 Mediates The Pathogenic Effect Of Yersinia Pestis Yopm In Liver Of C57bl/6 Mice And Contributes To Yopm's Function In Spleen, Zhan Ye, Amanda A. Gorman, Annette M. Uittenbogaard, Tanya Myers-Morales, Alan M. Kaplan, Donald A. Cohen, Susan C. Straley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found …

Cyclic Di-Gmp-Dependent Signaling Pathways In The Pathogenic Firmicute Listeria Monocytogenes, Li-Hong Chen, Volkan K. Köseoğlu, Zehra T. Güvener, Tanya Myers-Morales, Joseph M. Reed, Sarah E. F. D'Orazio, Kurt W. Miller, Mark Gomelsky

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We characterized key components and major targets of the c-di-GMP signaling pathways in the foodborne pathogen Listeria monocytogenes, identified a new c-di-GMP-inducible exopolysaccharide responsible for motility inhibition, cell aggregation, and enhanced tolerance to disinfectants and desiccation, and provided first insights into the role of c-di-GMP signaling in listerial virulence. Genome-wide genetic and biochemical analyses of c-di-GMP signaling pathways revealed that L. monocytogenes has three GGDEF domain proteins, DgcA (Lmo1911), DgcB (Lmo1912) and DgcC (Lmo2174), that possess diguanylate cyclase activity, and three EAL domain proteins, PdeB (Lmo0131), PdeC (Lmo1914) and PdeD (Lmo0111), that possess c-di-GMP phosphodiesterase activity. Deletion of all …

Vcam-1/Α4Β1 Integrin Interaction Is Crucial For Prompt Recruitment Of Immune T Cells Into The Brain During The Early Stage Of Reactivation Of Chronic Infection With Toxoplasma Gondii To Prevent Toxoplasmic Encephalitis, Qila Sa, Eri Ochiai, Tomoko Sengoku, Melinda E. Wilson, Morgan Brogli, Stephen Crutcher, Sara A. Michie, Baohui Xu, Laura Payne, Xisheng Wang, Yasuhiro Suzuki

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other …

The Development Of A Comprehensive Antifungal Susceptibility Testing Assay For Vulvovaginal Candidiasis Therapy, David Hardaker

Graduate School of Biomedical Sciences Theses and Dissertations

Vulvovaginal candidiasis is the most common fungal infection of the female urogenital tract, commonly caused by Candida albicans and C. glabrata. However, treatment can be difficult when caused by non-albicans strains due to resistance to the oral antifungal drug fluconazole. The mechanism through which strains of Candida, particularly C. glabrata, develop resistance to different antifungal classes has not been completely characterized. The ergosterol biosynthesis pathway, an important component of the cell membrane, is the major target of antifungals such as fluconazole, an inhibitor of the ERG 11 gene. Current research shows that an upregulation of specific genes in C. glabrata …

Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …

Oral Transmission Of Listeria Monocytogenes In Mice Via Ingestion Of Contaminated Food, Elsa N. Bou Ghanem, Tanya Myers-Morales, Grant S. Jones, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

L. monocytogenes are facultative intracellular bacterial pathogens that cause food borne infections in humans. Very little is known about the gastrointestinal phase of listeriosis due to the lack of a small animal model that closely mimics human disease. This paper describes a novel mouse model for oral transmission of L. monocytogenes. Using this model, mice fed L. monocytogenes-contaminated bread have a discrete phase of gastrointestinal infection, followed by varying degrees of systemic spread in susceptible (BALB/c/By/J) or resistant (C57BL/6) mouse strains. During the later stages of the infection, dissemination to the gall bladder and brain is observed. The …

Multifactorial Patterns Of Gene Expression In Colonic Epithelial Cells Predict Disease Phenotypes In Experimental Colitis, Aubrey Leigh Frantz, Maria E. C. Bruno, Eric William Rogier, Halide Tuna, Donald A. Cohen, Subbarao Bondada, Ralph Lakshman Chelvarajan, J. Anthony Brandon, C. Darrell Jennings, Charlotte S. Kaetzel

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background— The pathogenesis of inflammatory bowel disease (IBD) is complex and the need to identify molecular biomarkers is critical. Epithelial cells play a central role in maintaining intestinal homeostasis. We previously identified five “signature” biomarkers in colonic epithelial cells (CEC) that are predictive of disease phenotype in Crohn's disease. Here we investigate the ability of CEC biomarkers to define the mechanism and severity of intestinal inflammation.

Methods— We analyzed the expression of RelA, A20, pIgR, tumor necrosis factor (TNF), and macrophage inflammatory protein (MIP)-2 in CEC of mice with dextran sodium sulfate (DSS) acute colitis or T-cell-mediated chronic colitis. …

Role Of Phosphoinositide 3-Kinase – Akt Signaling Pathway In The Age-Related Cytokine Dysregulation In Splenic Macrophages Stimulated Via Tlr-2 Or Tlr-4 Receptors, Mosoka Papa Fallah, R. Lakshman Chelvarajan, Beth A. Garvy, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Age-associated defects in both B-lymphocytes and macrophages in elderly result in a reduction in the efficacy of vaccines to many Gram positive bacteria like Streptococcus pneumoniae. Splenic macrophages from aged mice have been shown to have a defect in production of pro-inflammatory cytokines (IL-6, IL-12, IL-1β, TNF-α) but exhibit increased production of IL-10 upon TLR4 ligation. Here we showed that aged macrophages demonstrate similar cytokine dysregulation phenotype upon stimulation with TLR2 ligands, or killed S. pneumoniae. We hypothesized that an age-associated increase in activity of phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway may be playing a causal role in …

Association Between Chronic Liver And Colon Inflammation During The Development Of Murine Syngeneic Graft-Versus-Host Disease, Jason Anthony Brandon, Jacqueline Perez-Rodriguez, C. Darrell Jennings, Donald A. Cohen, Vishal J. Sindhava, Subbarao Bondada, Alan M. Kaplan, J. Scott Bryson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The murine model of cyclosporine A (CsA)-induced syngeneic graft-versus-host disease (SGVHD) is a bone marrow (BM) transplantation model that develops chronic colon inflammation identical to other murine models of CD4⁺ T cell-mediated colitis. Interestingly, SGVHD animals develop chronic liver lesions that are similar to the early peribiliary inflammatory stages of clinical chronic liver disease, which is frequently associated with inflammatory bowel disease (IBD). Therefore, studies were initiated to investigate the chronic liver inflammation that develops in the SGVHD model. To induce SGVHD, mice were lethally irradiated, reconstituted with syngeneic BM, and treated with CsA. All of the SGVHD animals …

Cd19 Signaling Is Impaired In Murine Peritoneal And Splenic B-1 B Lymphocytes, Trivikram Dasu, Vishal Sindhava, Stephen H. Clarke, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells reside predominantly within the coelomic cavities, tonsils, Peyer's patches, spleen (a minor fraction – ∼5%) and are absent in the lymph nodes. They are the primary sources of natural IgM in the body. B-1 cells express polyreactive B cell receptors (BCRs) that cross react with self-antigens and are thus implicated in auto-immune disorders. Previously, we reported that peritoneal B-1 cells are deficient in CD19-mediated intracellular signals leading to Ca²⁺ mobilization. Here, we find that splenic B-1 cells, like peritoneal B-1 cells, are defective in Ca²⁺ release upon B cell activation by co-cross-linking BCR and CD19. In …

Accelerated High Fidelity Prion Amplification Within And Across Prion Species Barriers, Kristi M. Green, Joaquín Castilla, Tanya S. Seward, Dana L. Napier, Jean E. Jewell, Claudio Soto, Glenn C. Telling

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. Here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as Tg(CerPrP), as a substrate for in vitro generation of chronic wasting disease (CWD) prions by protein misfolding cyclic amplification (PMCA). Characterization of this infectivity in Tg(CerPrP) mice demonstrated that serial PMCA resulted in the high fidelity amplification of CWD prions with apparently unaltered properties. Using similar methods to amplify mouse RML prions and characterize the resulting novel cervid prions, we show that serial PMCA abrogated a transmission barrier …

Cd5 Plays An Inhibitory Role In The Suppressive Function Of Murine Cd4(+) Cd25(+) T(Reg) Cells., Trivikram Dasu, Joseph E Qualls, Halide Tuna, Chander Raman, Donald A Cohen, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A subset of CD4(+) T cells, the CD4(+) CD25(+) regulatory T (T(reg)) cells in the lymphoid organs and peripheral blood are known to possess suppressive function. Previous in vitro and in vivo studies have indicated that T cell receptor (TCR) signal is required for development of such 'natural regulatory (T(reg)) cells' and for activation of the effector function of CD4(+) CD25(+) regulatory T cells. CD5 is a cell surface molecule present on all T cells and a subtype of B lymphocytes, the B-1 cells, primarily localized to coelomic cavities, Peyer's patches, tonsils and spleen. CD5 acts as a negative regulator …

Cd5 Plays An Inhibitory Role In The Suppressive Function Of Murine Cd4+ Cd25+ TReg Cells, Trivikram Dasu, Joseph E. Qualls, Halide Tuna, Chander Raman, Donald A. Cohen, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A subset of CD4⁺ T cells, the CD4⁺ CD25⁺ regulatory T (T_reg) cells in the lymphoid organs and peripheral blood are known to possess suppressive function. Previous in vitro and in vivo studies have indicated that T cell receptor (TCR) signal is required for development of such ‘natural regulatory (T_reg) cells’ and for activation of the effector function of CD4⁺ CD25⁺ regulatory T cells. CD5 is a cell surface molecule present on all T cells and a subtype of B lymphocytes, the B-1 cells, primarily localized to coelomic cavities, Peyer's patches, …

The Role Of Mapks In B Cell Receptor-Induced Down-Regulation Of Egr-1 In Immature B Lymphoma Cells, Jiyuan Ke, Murali Gururajan, Anupam Kumar, Alan Simmons, Lilia Turcios, Ralph Lakshman Chelvarajan, David M. Cohen, David L. Wiest, John G. Monroe, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Cross-linking of the B cell receptor (BCR) on the immature B lymphoma cell line BKS-2 induces growth inhibition and apoptosis accompanied by rapid down-regulation of the immediate-early gene egr-1. In these lymphoma cells, egr-1 is expressed constitutively and has a prosurvival role, as Egr-1-specific antisense oligonucleotides or expression of a dominant-negative inhibitor of Egr-1 also prevented the growth of BKS-2 cells. Moreover, enhancement of Egr-1 protein with phorbol 12-myristate 13-acetate or an egr-1 expression vector rescued BKS-2 cells from BCR signal-induced growth inhibition. Nuclear run-on and mRNA stability assays indicated that BCR-derived signals act at the transcriptional level to …

Expression And Function Of Hoxc5 And Hoxc6 In The Murine Mammary Gland, Silvia Alejandra Garcia-Gasca

MUSC Theses and Dissertations

Homeotic genes encode transcription factors, believed to regulate cell proliferation, differentiation, as well as cell migration to create positional identities during embryogenesis. In the mouse, the Hox complex consists of at least 39 genes, organized into four clusters, in four different chromosomes. Hoxc5 and Hoxc6 are adjacent genes located in chromosome 15, and are expressed in the developing somites of the thoracic region and central nervous system with overlapping patterns. Both Hoxc5 and Hoxc6 are also expressed in the mammary gland. This study demonstrates that a targeted disruption of the Hoxc6 gene results in a failure of ductal development in …

Cellular Basis Of Decreased Immune Responses To Pneumococcal Vaccines In Aged Mice, Manju Garg, Wei Luo, Alan M. Kaplan, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Previously, model systems were developed in our laboratory to study murine immune responses to the 23-valent pneumococcal polysaccharide vaccine Pnu-Imune, both in vivo and in vitro (M. Garg and B. Subbarao, Infect. Immun. 60:2329-2336, 1992; M. Garg, A. M. Kaplan, and S. Bondada, J. Immunol. 152: 1589-1596, 1994). Using these systems, we found that aged mice did not respond to the vaccine in vivo or in vitro. Cell separation studies showed that the unresponsiveness of the aged spleen cells to the vaccine was not due to an intrinsic B-cell defect or to T-cell-mediated immunosuppression but resulted from an accessory cell …

Reversal Of Age-Associated Decline In Immune Response To Pnu-Imune Vaccine By Supplementation With The Steroid Hormone Dehydroepiandrosterone, Manju Garg, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Recently, we reported that murine antibody responses to the 23-valent pneumococcal polysaccharide (Pnu-Imune) vaccine declined with age. Here we present data to support the concept that age-associated immune defects are not only due to intrinsic defects in immune cells but are also due to extrinsic factors emanating from the neuroendocrine system. We found that supplementation with dehydroepiandrosterone, a steroid hormone known to be reduced in the aged, corrects the immune deficiency of aged mice and significantly enhanced their splenic immune responses to the Pnu-Imune vaccine.