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Full-Text Articles in Medicine and Health Sciences

Autophagy And Cell Wall Integrity Pathways Coordinately Regulate The Development And Pathogenicity Through Moatg4 Phosphorylation In Magnaporthe Oryzae, Pusheng Guo, Yurong Wang, Jiayun Xu, Zhixiang Yang, Ziqi Zhang, Jinyi Qian, Jiexiong Hu, Ziyi Yin, Leiyun Yang, Muxing Liu, Xinyu Liu, Gang Li, Haifeng Zhang, Ryan Rumsey, Ping Wang, Zhengguang Zhang Jan 2024

Autophagy And Cell Wall Integrity Pathways Coordinately Regulate The Development And Pathogenicity Through Moatg4 Phosphorylation In Magnaporthe Oryzae, Pusheng Guo, Yurong Wang, Jiayun Xu, Zhixiang Yang, Ziqi Zhang, Jinyi Qian, Jiexiong Hu, Ziyi Yin, Leiyun Yang, Muxing Liu, Xinyu Liu, Gang Li, Haifeng Zhang, Ryan Rumsey, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

Autophagy and Cell wall integrity (CWI) signaling are critical stress-responsive processes during fungal infection of host plants. In the rice blast fungus Magnaporthe oryzae, autophagy-related (ATG) proteins phosphorylate CWI kinases to regulate virulence; however, how autophagy interplays with CWI signaling to coordinate such regulation remains unknown. Here, we have identified the phosphorylation of ATG protein MoAtg4 as an important process in the coordination between autophagy and CWI in M. oryzae. The ATG kinase MoAtg1 phosphorylates MoAtg4 to inhibit the deconjugation and recycling of the key ATG protein MoAtg8. At the same time, MoMkk1, a core kinase of CWI, also phosphorylates …


Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette Jan 2024

Targeted Repression Of Topa By Crispri Reveals A Critical Function For Balanced Dna Topoisomerase I Activity In The Chlamydia Trachomatis Developmental Cycle, Li Shen, Leiqiong Gao, Abigail R. Swoboda, Scot P. Ouellette

School of Medicine Faculty Publications

Chlamydia trachomatis is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling Chlamydia developmental processes. Utilizing catalytically inactivated Cas12 (dCas12)-based clustered regularly interspaced short palindromic repeats interference (CRISPRi) technology, we demonstrate targeted knockdown of chromosomal topA transcription in C. trachomatis without detected toxicity of dCas12. Repression of topA impaired the developmental cycle of C. trachomatis mostly through disruption of its differentiation from a replicative form …


Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding Jan 2024

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …


Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low Dec 2023

Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low

School of Medicine Faculty Publications

Introduction Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. Methods and analysis This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and …


Cocaine Use Disorder Effects On Blood Oxytocin Levels And Oxtr Dna Methylation, Manassés Soares Souza, Breno Sanvicente-Vieira, Aline Zaparte, Talita Baptista, Maria Aparecida Nagai, Flávia Rotea Mangone, Ana Carolina Pavanelli, Thiago Wendt Viola, Rodrigo Grassi-Oliveira Sep 2023

Cocaine Use Disorder Effects On Blood Oxytocin Levels And Oxtr Dna Methylation, Manassés Soares Souza, Breno Sanvicente-Vieira, Aline Zaparte, Talita Baptista, Maria Aparecida Nagai, Flávia Rotea Mangone, Ana Carolina Pavanelli, Thiago Wendt Viola, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. …


Methionine Biosynthesis Enzyme Momet2 Is Required For Rice Blast Fungus Pathogenicity By Promoting Virulence Gene Expression Via Reducing 5mc Modification, Huimin Li, Pengcheng Mo, Jun Zhang, Zhuoer Xie, Xinyu Liu, Han Chen, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang Sep 2023

Methionine Biosynthesis Enzyme Momet2 Is Required For Rice Blast Fungus Pathogenicity By Promoting Virulence Gene Expression Via Reducing 5mc Modification, Huimin Li, Pengcheng Mo, Jun Zhang, Zhuoer Xie, Xinyu Liu, Han Chen, Leiyun Yang, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

The emergence of fungicide resistance severely threatens crop production by limiting the availability and application of established fungicides. Therefore, it is urgent to identify new fungicidal targets for controlling plant diseases. Here, we characterized the function of a conserved homoserine O-acetyltransferase (HOA) from the rice blast fungus Magnaporthe oryzae that could serve as the candidate antifungal target. Deletion of the MoMET2 and MoCYS2 genes encoding HOAs perturbed the biosynthesis of methionine and S-adenyl methionine, a methyl group donor for epigenetic modifications, and severely attenuated the development and virulence of M. oryzae. The ΔMomet2 mutant is significantly increased in 5-methylcytosine (5mC) …


Her3 Functions As An Effective Therapeutic Target In Triple Negative Breast Cancer To Potentiate The Antitumor Activity Of Gefitinib And Paclitaxel, Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu Sep 2023

Her3 Functions As An Effective Therapeutic Target In Triple Negative Breast Cancer To Potentiate The Antitumor Activity Of Gefitinib And Paclitaxel, Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu

School of Medicine Faculty Publications

Background: Triple negative breast cancer (TNBC) represents a significant clinical challenge. Chemotherapy remains the mainstay for a large part of TNBC patients, whereas drug resistance and tumor recurrence frequently occur. It is in urgent need to identify novel molecular targets for TNBC and develop effective therapy against the aggressive disease. Methods: Immunohistochemistry was performed to examine the expression of HER3 in TNBC samples. Western blots were used to assess protein expression and activation. Cell proliferation and viability were determined by cell growth (MTS) assays. TCGA databases were analyzed to correlate HER3 mRNA expression with the clinical outcomes of TNBC patients. …


Time Is Ticking For Cervical Cancer, Vijay Kumar, Caitlin Bauer, John H. Stewart Jun 2023

Time Is Ticking For Cervical Cancer, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Medicine Faculty Publications

Cervical cancer (CC) is a major health problem among reproductive-age females and comprises a leading cause of cancer-related deaths. Human papillomavirus (HPV) is the major risk factor associated with CC incidence. However, lifestyle is also a critical factor in CC pathogenesis. Despite HPV vaccination introduction, the incidence of CC is increasing worldwide. Therefore, it becomes critical to understand the CC tumor immune microenvironment (TIME) to develop immune cell-based vaccination and immunotherapeutic approaches. The current article discusses the immune environment in the normal cervix of adult females and its role in HPV infection. The subsequent sections discuss the alteration of different …


Relative And Quantitative Characterization Of The Bovine Bacterial Ocular Surface Microbiome In The Context Of Suspected Ocular Squamous Cell Carcinoma, Hannah B. Gafen, Chin-Chi Liu, Nikole E. Ineck, Clare M. Scully, Melanie A. Mironovich, Lauren Guarneri, Christopher M. Taylor, Meng Luo, Marina L. Leis, Erin M. Scott, Renee T. Carter, Andrew C. Lewin Jun 2023

Relative And Quantitative Characterization Of The Bovine Bacterial Ocular Surface Microbiome In The Context Of Suspected Ocular Squamous Cell Carcinoma, Hannah B. Gafen, Chin-Chi Liu, Nikole E. Ineck, Clare M. Scully, Melanie A. Mironovich, Lauren Guarneri, Christopher M. Taylor, Meng Luo, Marina L. Leis, Erin M. Scott, Renee T. Carter, Andrew C. Lewin

School of Medicine Faculty Publications

The ocular surface microbiome is altered in certain disease states. The aim of this study was to characterize the bovine bacterial ocular surface microbiome (BBOSM) in the context of ocular squamous cell carcinoma (OSCC). The conjunctiva of normal (n = 28) and OSCC (n = 10) eyes of cows aged 2 to 13 years from two farms in Louisiana and Wyoming were sampled using individual sterile swabs. DNA extraction followed by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and real-time polymerase chain reaction (RT-PCR) were performed to, respectively, assess the relative and absolute BBOSM. Discriminant analysis (DA) was performed using …


Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura Dec 2022

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura

School of Medicine Faculty Publications

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …


Effects Of Substance Use Disorder On Oxidative And Antioxidative Stress Markers: A Systematic Review And Meta-Analysis, Thiago Wendt Viola, Rodrigo Orso, Luisa Fossati Florian, Miguel Gomes Garcia, Marco Giovanni Signor Gomes, Eduarda Mascarenhas Mardini, João Paulo Ottolia Niederauer, Aline Zaparte, Rodrigo Grassi-Oliveira Nov 2022

Effects Of Substance Use Disorder On Oxidative And Antioxidative Stress Markers: A Systematic Review And Meta-Analysis, Thiago Wendt Viola, Rodrigo Orso, Luisa Fossati Florian, Miguel Gomes Garcia, Marco Giovanni Signor Gomes, Eduarda Mascarenhas Mardini, João Paulo Ottolia Niederauer, Aline Zaparte, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

Recently, it has been suggested that central and peripheral toxicities identified in persons with substance use disorder (SUD) could be partially associated with an imbalance in reactive oxygen species and antioxidant defenses. We conducted a systematic review and meta-analysis to investigate whether SUD is associated with oxidative stress and to identify biomarkers possibly more affected by this condition. We have included studies that analysed oxidant and antioxidant markers in individuals with SUD caused by stimulants, alcohol, nicotine, opioids, and others (cannabis, inhalants, and polysubstance use). Our analysis showed that persons with SUD show higher oxidant markers and lower antioxidant markers …


Incident Chlamydia Trachomatis Infection In A High School Population, Jacques M. Nsuami, Wato Nsa, Catherine L. Cammarata, David H. Martin, Stephanie N. Taylor Sep 2022

Incident Chlamydia Trachomatis Infection In A High School Population, Jacques M. Nsuami, Wato Nsa, Catherine L. Cammarata, David H. Martin, Stephanie N. Taylor

School of Medicine Faculty Publications

Prospective cohort studies of sexually transmitted infections (STIs) are logistically impractical owing to time and expenses. In schools, students are readily available for school-related follow-ups and monitoring. Capitalizing on the logistics that society already commits to ensure regular attendance of adolescents in school, a school-based STI screening in New Orleans made it possible to naturally observe the occurrence of chlamydia and to determine its incidence among 14–19-year-old adolescents. Among participants screened repeatedly, we calculated incidence rates, cumulative incidence, and incidence times. Male (n = 3820) and female (n = 3501) students were observed for 6251 and 5143 person-years, respectively, during …


Active And Passive Immunization With An Anti-Methamphetamine Vaccine Attenuates The Behavioral And Cardiovascular Effects Of Methamphetamine, Colin N. Haile, Kurt J. Varner, Xia Huijing, Reetakshi Arora, Frank M. Orson, Thomas R. Kosten, Therese A. Kosten Sep 2022

Active And Passive Immunization With An Anti-Methamphetamine Vaccine Attenuates The Behavioral And Cardiovascular Effects Of Methamphetamine, Colin N. Haile, Kurt J. Varner, Xia Huijing, Reetakshi Arora, Frank M. Orson, Thomas R. Kosten, Therese A. Kosten

School of Medicine Faculty Publications

Background: Methamphetamine use disorder (MUD) is a growing health concern with no FDA-approved treatment. The present series of studies build upon our previous work developing an anti-methamphetamine (MA) vaccine for MUD. We determined the effects of a formulation that included tetanus-toxoid (TT) conjugated to succinyl-methamphetamine (TT-SMA) adsorbed onto aluminum hydroxide (alum) in combination with the novel Toll-Like Receptor-5 agonist, entolimod. Methods: Mice were vaccinated (0, 3, 6 weeks) with TT-SMA+alum and various doses of entolimod to determine an optimal dose for enhancing immunogenicity against MA. Functional effects were then assessed using MA-induced locomotor activation in mice. Experiments using passive immunization …


Sars-Cov-2 Invasion And Pathological Links To Prion Disease, Walter J. Lukiw, Vivian R. Jaber, Aileen I. Pogue, Yuhai Zhao Sep 2022

Sars-Cov-2 Invasion And Pathological Links To Prion Disease, Walter J. Lukiw, Vivian R. Jaber, Aileen I. Pogue, Yuhai Zhao

School of Medicine Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 disease, is a highly infectious and transmissible viral pathogen that continues to impact human health globally. Nearly ~600 million people have been infected with SARS-CoV-2, and about half exhibit some degree of continuing health complication, generically referred to as long COVID. Lingering and often serious neurological problems for patients in the post-COVID-19 recovery period include brain fog, behavioral changes, confusion, delirium, deficits in intellect, cognition and memory issues, loss of balance and coordination, problems with vision, visual processing and hallucinations, encephalopathy, encephalitis, neurovascular or cerebrovascular insufficiency, and/or …


Solid-State Nmr Analysis Of Unlabeled Fungal Cell Walls From Aspergillus And Candida Species, Liyanage D. Fernando, Malitha C. Dickwella Widanage, S. Chandra Shekar, Frederic Mentink-Vigier, Ping Wang, Sungsool Wi, Tuo Wang Jul 2022

Solid-State Nmr Analysis Of Unlabeled Fungal Cell Walls From Aspergillus And Candida Species, Liyanage D. Fernando, Malitha C. Dickwella Widanage, S. Chandra Shekar, Frederic Mentink-Vigier, Ping Wang, Sungsool Wi, Tuo Wang

School of Medicine Faculty Publications

Fungal infections cause high mortality in immunocompromised individuals, which has emerged as a significant threat to human health. The efforts devoted to the development of antifungal agents targeting the cell wall polysaccharides have been hindered by our incomplete picture of the assembly and remodeling of fungal cell walls. High-resolution solid-state nuclear magnetic resonance (ss NMR) studies have substantially revised our understanding of the polymorphic structure of polysaccharides and the nanoscale organization of cell walls in Aspergillus fumigatus and multiple other fungi. However, this approach requires 13C/15N-enrichment of the sample being studied, severely restricting its application. Here we employ the dynamic …


Increased Inflammatory Low-Density Neutrophils In Severe Obesity And Effect Of Bariatric Surgery: Results From Case-Control And Prospective Cohort Studies, Maria Dulfary Sanchez-Pino, William S. Richardson, Jovanny Zabaleta, Ramesh Thylur Puttalingaiah, Andrew G. Chapple, Jiao Liu, Yonghyan Kim, Michelle Ponder, Randi Dearmitt, Lyndsey Buckner Baiamonte, Dorota Wyczechowska, Liqin Zheng, Amir A. Al-Khami, Jone Garai, Rachel Martini, Melissa Davis, Jessica Koller Gorham, James B. Wooldridge, Paulo C. Rodriguez, Lucio Miele, Augusto C. Ochoa Mar 2022

Increased Inflammatory Low-Density Neutrophils In Severe Obesity And Effect Of Bariatric Surgery: Results From Case-Control And Prospective Cohort Studies, Maria Dulfary Sanchez-Pino, William S. Richardson, Jovanny Zabaleta, Ramesh Thylur Puttalingaiah, Andrew G. Chapple, Jiao Liu, Yonghyan Kim, Michelle Ponder, Randi Dearmitt, Lyndsey Buckner Baiamonte, Dorota Wyczechowska, Liqin Zheng, Amir A. Al-Khami, Jone Garai, Rachel Martini, Melissa Davis, Jessica Koller Gorham, James B. Wooldridge, Paulo C. Rodriguez, Lucio Miele, Augusto C. Ochoa

School of Medicine Faculty Publications

Background: Low-density neutrophils (LDN) are increased in several inflammatory diseases and may also play a role in the low-grade chronic inflammation associated with obesity. Here we explored their role in obesity, determined their gene signatures, and assessed the effect of bariatric surgery. Methods: We compared the number, function, and gene expression profiles of circulating LDN in morbidly obese patients (MOP, n=27; body mass index (BMI) > 40 Kg/m2) and normal-weight controls (NWC, n=20; BMI < 25 Kg/m2) in a case-control study. Additionally, in a prospective longitudinal study, we measured changes in the frequency of LDN after bariatric surgery (n=36) and tested for associations with metabolic and inflammatory parameters. Findings: LDN and inflammatory markers were significantly increased in MOP compared to NWC. Transcriptome analysis showed increased neutrophil-related gene expression signatures associated with inflammation, neutrophil activation, and immunosuppressive function. However, LDN did not suppress T cells proliferation and produced low levels of reactive oxygen species (ROS). Circulating LDN in MOP significantly decreased after bariatric surgery in parallel with BMI, metabolic syndrome, and inflammatory markers. Interpretation: Obesity increases LDN displaying an inflammatory gene signature. Our results suggest that LDN may represent a neutrophil subset associated with chronic inflammation, a feature of obesity that has been previously associated with the appearance and progression of co-morbidities. Furthermore, bariatric surgery, as an efficient therapy for severe obesity, reduces LDN in circulation and improves several components of the metabolic syndrome supporting its recognized anti-inflammatory and beneficial metabolic effects. Funding: This work was supported in part by grants from the National Institutes of Health (NIH; 5P30GM114732-02, P20CA233374 – A. Ochoa and L. Miele), Pennington Biomedical NORC (P30DK072476 – E. Ravussin & LSU-NO Stanley S. Scott Cancer Center and Louisiana Clinical and Translational Science Center (LACaTS; U54-GM104940 – J. Kirwan).


Moerv29 Promotes Apoplastic Effector Secretion Contributing To Virulence Of The Rice Blast Fungus Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Danyu Shen, Han Chen, Haifeng Zhang, Ping Wang, Zhengguang Zhang Nov 2021

Moerv29 Promotes Apoplastic Effector Secretion Contributing To Virulence Of The Rice Blast Fungus Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Danyu Shen, Han Chen, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Medicine Faculty Publications

During plant-pathogenic fungi and host plants interactions, numerous pathogen-derived proteins are secreted resulting in the activation of the unfolded protein response (UPR) pathway. For efficient trafficking of secretory proteins, including those important in disease progression, the cytoplasmic coat protein complex II (COPII) exhibits a multifunctional role whose elucidation remains limited. Here, we discovered that the COPII cargo receptor MoErv29 functions as a target of MoHac1, a previously identified transcription factor of the UPR pathway. In Magnaporthe oryzae, deletion of MoERV29 severely affected the vegetative growth, conidiation and biotrophic invasion of the fungus in susceptible rice hosts. We demonstrated that MoErv29 …


Biophysical Evaluation Of Rhesus Macaque Fc Gamma Receptors Reveals Similar Igg Fc Glycoform Preferences To Human Receptors, Andrew R. Crowley, Nana Yaw Osei-Owusu, Gillian Dekkers, Wenda Gao, Manfred Wuhrer, Diogo M. Magnani, Keith A. Reimann, Seth H. Pincus, Gestur Vidarsson, Margaret E. Ackerman Oct 2021

Biophysical Evaluation Of Rhesus Macaque Fc Gamma Receptors Reveals Similar Igg Fc Glycoform Preferences To Human Receptors, Andrew R. Crowley, Nana Yaw Osei-Owusu, Gillian Dekkers, Wenda Gao, Manfred Wuhrer, Diogo M. Magnani, Keith A. Reimann, Seth H. Pincus, Gestur Vidarsson, Margaret E. Ackerman

School of Medicine Faculty Publications

Rhesus macaques are a common non-human primate model used in the evaluation of human monoclonal antibodies, molecules whose effector functions depend on a conserved N-linked glycan in the Fc region. This carbohydrate is a target of glycoengineering efforts aimed at altering antibody effector function by modulating the affinity of Fcγ receptors. For example, a reduction in the overall core fucose content is one such strategy that can increase antibody-mediated cellular cytotoxicity by increasing Fc-FcγRIIIa affinity. While the position of the Fc glycan is conserved in macaques, differences in the frequency of glycoforms and the use of an alternate monosaccharide in …


Fulminant Eosinophilic Myocarditis And Vt Storm, Kyle R. Hoppens, Hamid R. Alai, Jelena Surla, Hina O. Khokhar, Robert C. Hendel Mar 2021

Fulminant Eosinophilic Myocarditis And Vt Storm, Kyle R. Hoppens, Hamid R. Alai, Jelena Surla, Hina O. Khokhar, Robert C. Hendel

School of Medicine Faculty Publications

Eosinophilic myocarditis is a rare and frequently fatal disease that is often undiagnosed until autopsy. We report a case of eosinophilic myocarditis with an unusual initial presentation of palpitations that subsequently evolved into ventricular tachycardia storm and death within 4 days.


Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan Oct 2020

Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan

School of Medicine Faculty Publications

Scc4 is an unusual bi-functional protein from Chlamydia trachomatis (CT) that functions as a type III secretion system (T3SS) chaperone and an RNA polymerase (RNAP)-binding protein. Both functions require interactions with protein partners during specific stages of the CT developmental cycle. As a T3SS chaperone, Scc4 binds Scc1 during the late stage of development to form a heterodimer complex, which chaperones the essential virulence effector, CopN. During the early-middle stage of development, Scc4 regulates T3SS gene expression by binding the σ66-containing RNAP holoenzyme. In order to study the structure and association mechanism of the Scc4:Scc1 T3SS chaperone complex using nuclear …


Targeting Parp-1 With Metronomic Therapy As A New Approach To Modulate Mdsc Function And Enhance Anti-Pd1 Immunotherapy In Colon Cancer, Salome Valentina Ibba, Mohamed Ghonim, Abdelmetalab Tarhuni, Matthew Dean, Hamid Boulares, Augusto Ochoa, Youssef Errami, Ali Elbahraway, Ilyes Benslimane, Dorota Wyczechowska, Luis Del Valle, Amir Al-Khami, Hanh Luu Nov 2019

Targeting Parp-1 With Metronomic Therapy As A New Approach To Modulate Mdsc Function And Enhance Anti-Pd1 Immunotherapy In Colon Cancer, Salome Valentina Ibba, Mohamed Ghonim, Abdelmetalab Tarhuni, Matthew Dean, Hamid Boulares, Augusto Ochoa, Youssef Errami, Ali Elbahraway, Ilyes Benslimane, Dorota Wyczechowska, Luis Del Valle, Amir Al-Khami, Hanh Luu

School of Medicine Faculty Publications

34th Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer - Part 1, November 6 - 10, 2019, National Harbor, MD


Role Of Eif4g1 In Non-Small Cell Lung Cancer Pathogenesis And Targeted Therapy, Zhiqiang Qin, Lu Dai, Luis Del Valle Jul 2019

Role Of Eif4g1 In Non-Small Cell Lung Cancer Pathogenesis And Targeted Therapy, Zhiqiang Qin, Lu Dai, Luis Del Valle

School of Medicine Faculty Publications

American Association for Cancer Research Annual Meeting 2019, March 29 - April 3, 2019, Atlanta, GA


Cd147 And Downstream Adamtss Promote The Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus Infected Endothelial Cells, Lu Dai, Jimena Trillo-Tinoco, Yihan Chen, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Augusto C. Ochoa, Jovanny Zabaleta, Bryan P. Toole, Zhiqiang Qin Jan 2016

Cd147 And Downstream Adamtss Promote The Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus Infected Endothelial Cells, Lu Dai, Jimena Trillo-Tinoco, Yihan Chen, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Augusto C. Ochoa, Jovanny Zabaleta, Bryan P. Toole, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's sarcoma (KS), which preferentially arise in immunocompromised patients and lack effective therapeutic options. We have previously shown that KSHV or viral protein LANA up-regulates the glycoprotein CD147, thereby inducing primary endothelial cell invasiveness. In the current study, we identify the global network controlled by CD147 in KSHV-infected endothelial cells using Illumina microarray analysis. Among downstream genes, two specific metalloproteases, ADAMTS1 and 9, are strongly expressed in AIDS-KS tissues and contribute to KSHV-infected endothelial cell invasiveness through up-regulation of IL-6 and VEGF. By using a KS-like nude …


Ceramides Promote Apoptosis For Virus-Infected Lymphoma Cells Through Induction Of Ceramide Synthases And Viral Lytic Gene Expression, Lu Dai, Jimena Trillo-Tinoco, Aiping Bai, Yihan Chen, Jacek Bielawski, Luis Del Valle, Charles D. Smith, Augusto C. Ochoa, Zhiqiang Qin, Chris Parsons Jul 2015

Ceramides Promote Apoptosis For Virus-Infected Lymphoma Cells Through Induction Of Ceramide Synthases And Viral Lytic Gene Expression, Lu Dai, Jimena Trillo-Tinoco, Aiping Bai, Yihan Chen, Jacek Bielawski, Luis Del Valle, Charles D. Smith, Augusto C. Ochoa, Zhiqiang Qin, Chris Parsons

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for several human cancers including primary effusion lymphoma (PEL), a rapidly progressive malignancy arising preferentially in immunocompromised patients. With conventional chemotherapy, PEL continues to portend high mortality, dictating the development of novel therapeutic strategies. Sphingosine kinase 2 (SphK2) represents a key gatekeeper for sphingolipid metabolism, responsible for conversion of ceramides to sphingosine-1-phosphate (S1P). We have previously demonstrated that targeting SphK2 using a novel selective inhibitor, ABC294640, leads to intracellular accumulation of ceramides and induces apoptosis for KSHV-infected PEL cells, while suppressing tumor progression in vivo. In the current study, we sought to …


Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin Feb 2014

Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells …


Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya Nov 2011

Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya

School of Medicine Faculty Publications

Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release …