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B16: Chikungunya Virus Time Course Infection Of Human Macrophages, Madison Gray, Israel Guerrero-Arguero, Antonio Solis Leal, Richard Robison, Brad Burges, Brett Pickett 2021 Brigham Young University - Provo

B16: Chikungunya Virus Time Course Infection Of Human Macrophages, Madison Gray, Israel Guerrero-Arguero, Antonio Solis Leal, Richard Robison, Brad Burges, Brett Pickett

Annual Research Symposium

Chikungunya virus (CHIKV) is an Alphavirus spread by Aedes spp. mosquitoes and is responsible for infecting 1.1 million people per year worldwide, including a large epidemic in the western hemisphere in 2014-2015. During the body’s immune response to CHIKV, human macrophages become infected after phagocytosis of CHIKV and undergo induced apoptosis, catalyzing the virus spread in the body. It is presently unclear what macrophage genes, functions, and intracellular signaling pathways are impacted during the early, intermediate, and late stages of CHIKV infection. Therefore we quantified the transcriptional response of human macrophage cells infected with CHIKV at two different ...


Effectiveness Of Pathogen-Specific Passive Antibodies To Mitigate Infectious Diseases In Apis Mellifera, Tanner Nordseth 2021 University of South Dakota

Effectiveness Of Pathogen-Specific Passive Antibodies To Mitigate Infectious Diseases In Apis Mellifera, Tanner Nordseth

Honors Thesis

Honeybees (Apis mellifera) are widely recognized as a vital part of the global ecosystem and the world's food supply due to their pivotal role in the pollination of both natural and agricultural flora. Colony Collapse Disorder (CCD) is an emerging phenomenon characterized by a colony's worker bees deserting the hive and leaving the queen behind. This usually results in colony failure. CCD is a multifactorial issue, with many environmental stressors and pathogens playing a role. Deformed Wing Virus (DWV) has been identified as a leading cause in this phenomenon. Paenibacillus larvae (P. larvae) is another lethal pathogen that ...


H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq 2021 University of Sargodha, Sargodha

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data was gathered following the contrasting and relative situations of 1918 as well as the 2009 pandemic in ...


Immune Checkpoint Inhibitor Therapy In Hiv-Associated Merkel Cell Carcinoma: A Case Series Of 3 Patients., Song Y Park, Candice Church, Nora A Alexander, Michi M Shinohara, Kelly G Paulson, Karl D Lewis, Nancy S Lee, Paul Nghiem 2021 Swedish Cancer Institute, Seattle/Edmonds, Washington.

Immune Checkpoint Inhibitor Therapy In Hiv-Associated Merkel Cell Carcinoma: A Case Series Of 3 Patients., Song Y Park, Candice Church, Nora A Alexander, Michi M Shinohara, Kelly G Paulson, Karl D Lewis, Nancy S Lee, Paul Nghiem

Articles, Abstracts, and Reports

No abstract provided.


Identification Of A Neutralizing Epitope Within Minor Repeat Region Of Plasmodium Falciparum Cs Protein, J. Mauricio Calvo-Calle, Robert Mitchell, Rita Altszuler, Caroline Othoro, Elizabeth Nardin 2021 University of Massachusetts Medical School

Identification Of A Neutralizing Epitope Within Minor Repeat Region Of Plasmodium Falciparum Cs Protein, J. Mauricio Calvo-Calle, Robert Mitchell, Rita Altszuler, Caroline Othoro, Elizabeth Nardin

Open Access Publications by UMMS Authors

Malaria remains a major cause of morbidity and mortality worldwide with 219 million infections and 435,000 deaths predominantly in Africa. The infective Plasmodium sporozoite is the target of a potent humoral immune response that can protect murine, simian and human hosts against challenge by malaria-infected mosquitoes. Early murine studies demonstrated that sporozoites or subunit vaccines based on the sporozoite major surface antigen, the circumsporozoite (CS) protein, elicit antibodies that primarily target the central repeat region of the CS protein. In the current murine studies, using monoclonal antibodies and polyclonal sera obtained following immunization with P. falciparum sporozoites or synthetic ...


Investigation Of A Monoclonal Antibody Against Enterotoxigenic Escherichia Coli, Expressed As Secretory Iga1 And Iga2 In Plants, Audrey Y-H. Teh, Lisa A. Cavacini, Yue Hu, Ozan S. Kumru, Jian Xiong, David T. Bolick, Sangeeta B. Joshi, Clemens Grunwald-Gruber, Friedrich Altmann, Mark S. Klempner, Richard L. Guerrant, David B. Volkin, Yang Wang, Julian K-C. Ma 2021 St. George's University of London

Investigation Of A Monoclonal Antibody Against Enterotoxigenic Escherichia Coli, Expressed As Secretory Iga1 And Iga2 In Plants, Audrey Y-H. Teh, Lisa A. Cavacini, Yue Hu, Ozan S. Kumru, Jian Xiong, David T. Bolick, Sangeeta B. Joshi, Clemens Grunwald-Gruber, Friedrich Altmann, Mark S. Klempner, Richard L. Guerrant, David B. Volkin, Yang Wang, Julian K-C. Ma

Open Access Publications by UMMS Authors

Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. SIgA1 and SIgA2 forms of mAb 68-81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. N-linked glycosylation was assessed by rapid ...


The Intellectual Property Of Covid-19, Ana Santos Rutschman 2021 Saint Louis University School of Law

The Intellectual Property Of Covid-19, Ana Santos Rutschman

All Faculty Scholarship

The response to COVID-19 is indissolubly tied to intellectual property. In an increasingly globalized world in which infectious disease pathogens travel faster and wider than before, the development of vaccines, treatments and other forms of medical technology has become an integral part of public health preparedness and response frameworks. The development of these technologies, and to a certain extent the allocation and distribution of resulting outputs, is informed by intellectual property regimes. These regimes influence the commitment of R&D resources, shape scientific collaborations and, in some cases, may condition the widespread availability of emerging technologies. As seen throughout this ...


Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon 2020 John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and AJCC stage III patients that are ...


Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu 2020 University of Nebraska Medical Center

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial ...


Targeting Cd5 To Enhance Immune T Cell Activation And Function In Treatment Of Solid Tumours, Faizah Alotaibi 2020 The University of Western Ontario

Targeting Cd5 To Enhance Immune T Cell Activation And Function In Treatment Of Solid Tumours, Faizah Alotaibi

Electronic Thesis and Dissertation Repository

CD5 is a member of scavenger receptor cysteine-rich superfamily that is expressed primarily on T cells. It can attenuate T-cell receptor signaling and impair cytotoxic T lymphocyte (CTL) activation and is a therapeutic targetable tumour antigen expressed on leukemic T and B cells. However, the potential therapeutic effect of functionally blocking CD5 to increase T cell anti-tumour activity against tumours (including solid tumours) has not been explored. CD5- solid tumours in CD5 knockout mice display increased in anti-tumour immunity. Hence, blocking CD5 function may have a potential therapeutic effect by enhancing CTL function. Here, I assessed CD5 levels in T ...


Immunotherapy For Infarcts: In Vivo Postinfarction Macrophage Modulation Using Intramyocardial Microparticle Delivery Of Map4k4 Small Interfering Rna, Jun Luo, Matthew S. Weaver, Timothy P. Fitzgibbons, Myriam Aouadi, Michael P. Czech, Margaret D. Allen 2020 Benaroya Research Institute at Virginia Mason

Immunotherapy For Infarcts: In Vivo Postinfarction Macrophage Modulation Using Intramyocardial Microparticle Delivery Of Map4k4 Small Interfering Rna, Jun Luo, Matthew S. Weaver, Timothy P. Fitzgibbons, Myriam Aouadi, Michael P. Czech, Margaret D. Allen

Open Access Publications by UMMS Authors

The myeloid cells infiltrating the heart early after acute myocardial infarction elaborate a secretome that largely orchestrates subsequent ventricular wall repair. Regulating this innate immune response could be a means to improve infarct healing. To pilot this concept, we utilized (beta1,3-d-) glucan-encapsulated small interfering RNA (siRNA)-containing particles (GeRPs), targeting mononuclear phagocytes, delivered to mice as a one-time intramyocardial injection immediately after acute infarction. Findings demonstrated that cardiac macrophages phagocytosed GeRPs in vivo and had little systemic dissemination, thus providing a means to deliver local therapeutics. Acute infarcts were then injected in vivo with phosphate-buffered saline (PBS; vehicle) or ...


Subclonal Evolution Of Chronic Lymphocytic Leukemia After Allogeneic T Cell Therapies, Haven Garber 2020 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Subclonal Evolution Of Chronic Lymphocytic Leukemia After Allogeneic T Cell Therapies, Haven Garber

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Subclonal evolution of chronic lymphocytic leukemia after allogeneic T-cell therapies

Haven Garber, MD

Advisory Professor: Jeffrey Molldrem, MD

Intratumoral genetic heterogeneity describes the molecular differences among subclones within a tumor and is a major barrier to effective therapy in many solid and liquid cancers, including chronic lymphocytic leukemia (CLL). Rare, treatment-resistant subclones can expand to compose relapsed disease during tumor evolution. Examination of malignant evolution in the context of specific treatment provides insight into the molecular lesions that mediate therapeutic response and resistance. Both chemotherapy and targeted therapy were shown to precipitate CLL subclonal evolution. We hypothesized that allogeneic T-cell ...


In Silico Modelling For The Treatment Of Gastric Cancer, Leonardo F. Martinez, Diana Gamboa, Paul A. Valle 2020 Tijuana Institute of Technology, Mexico

In Silico Modelling For The Treatment Of Gastric Cancer, Leonardo F. Martinez, Diana Gamboa, Paul A. Valle

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.


Iga As A Potential Candidate For Enteric Monoclonal Antibody Therapeutics With Improved Gastrointestinal Stability, Aaron L. Wallace, Matthew I. Schneider, Jacqueline R. Toomey, Ryan M. Schneider, Mark S. Klempner, Yang Wang, Lisa A. Cavacini 2020 University of Massachusetts Medical School

Iga As A Potential Candidate For Enteric Monoclonal Antibody Therapeutics With Improved Gastrointestinal Stability, Aaron L. Wallace, Matthew I. Schneider, Jacqueline R. Toomey, Ryan M. Schneider, Mark S. Klempner, Yang Wang, Lisa A. Cavacini

Open Access Publications by UMMS Authors

Mucosal surfaces of the gastrointestinal tract play an important role in immune homeostasis and defense and may be compromised by enteric disorders or infection. Therapeutic intervention using monoclonal antibody (mAb) offers the potential for treatment with minimal off-target effects as well as the possibility of limited systemic exposure when administered orally. Critically, to achieve efficacy at luminal surfaces, mAb must remain stable and functionally active in the gastrointestinal environment. To better understand the impact of isotype, class, and molecular structure on the intestinal stability of recombinant antibodies, we used an in vitro simulated intestinal fluid (SIF) assay to evaluate a ...


Harnessing Cellular Senescence For Cancer Immunotherapy, Marcus Ruscetti 2020 University of Massachusetts Medical School

Harnessing Cellular Senescence For Cancer Immunotherapy, Marcus Ruscetti

University of Massachusetts Medical School Publications

Presented virtually during the "New Faculty Talks" session at the 25th Annual University of Massachusetts Medical School Research Retreat 2020 on October 26, 2020.


Development Of Complement Factor H-Based Immunotherapeutic Molecules In Tobacco Plants Against Multidrug-Resistant Neisseria Gonorrhoeae, Jutamas Shaughnessy, Y. Tran, Bo Zheng, Rosane B. DeOliveira, Sunita Gulati, Wen-Chao Song, James M. Maclean, Keith L. Wycoff, Sanjay Ram 2020 University of Massachusetts Medical School

Development Of Complement Factor H-Based Immunotherapeutic Molecules In Tobacco Plants Against Multidrug-Resistant Neisseria Gonorrhoeae, Jutamas Shaughnessy, Y. Tran, Bo Zheng, Rosane B. Deoliveira, Sunita Gulati, Wen-Chao Song, James M. Maclean, Keith L. Wycoff, Sanjay Ram

Open Access Publications by UMMS Authors

Novel therapeutics against the global threat of multidrug-resistant Neisseria gonorrhoeae are urgently needed. Gonococci possess several mechanisms to evade killing by human complement, including binding of factor H (FH), a key inhibitor of the alternative pathway. FH comprises 20 short consensus repeat (SCR) domains organized in a head-to-tail manner as a single chain. N. gonorrhoeae binds two regions in FH; domains 6 and 7 and domains 18 through 20. We designed a novel anti-infective immunotherapeutic molecule that fuses domains 18-20 of FH containing a D-to-G mutation in domain 19 at position 1119 (called FH*) with human IgG1 Fc. FH*/Fc ...


Peptidylarginine Deiminase 2 Has Potential As Both A Biomarker And Therapeutic Target Of Sepsis, Yuzi Tian, Santanu Mondal, Paul R. Thompson, Yongqing Li 2020 Central South University

Peptidylarginine Deiminase 2 Has Potential As Both A Biomarker And Therapeutic Target Of Sepsis, Yuzi Tian, Santanu Mondal, Paul R. Thompson, Yongqing Li

Open Access Publications by UMMS Authors

Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes that are involved in a variety of human disorders, including cancer and autoimmune diseases. Although targeting PAD4 has shown no benefit in sepsis, the role of PAD2 remains unknown. Here, we report that PAD2 is engaged in sepsis and sepsis-induced acute lung injury in both human patients and mice. Pad2-/- or selective inhibition of PAD2 by a small molecule inhibitor increased survival and improved overall outcomes in mouse models of sepsis. Pad2 deficiency decreased neutrophil extracellular trap (NET) formation. Importantly, Pad2 deficiency inhibited Caspase-11-dependent pyroptosis in vivo and in vitro. Suppression ...


An In-Depth Investigation Of The Safety And Immunogenicity Of An Inactivated Sars-Cov-2 Vaccine [Preprint], Jing Pu, Shan Lu, Qihan Li 2020 Peking Union Medical College

An In-Depth Investigation Of The Safety And Immunogenicity Of An Inactivated Sars-Cov-2 Vaccine [Preprint], Jing Pu, Shan Lu, Qihan Li

University of Massachusetts Medical School Faculty Publications

BACKGROUND: 50 In-depth investigations of the safety and immunogenicity of inactivated SARS-CoV-2 vaccines 51 are needed. 52

METHOD: 53 In a phase I randomized, double-blinded, and placebo-controlled trial involving 192 healthy 54 adults 18-59 years of age, two injections of three different doses (50 EU, 100 EU and 150 EU) 55 of an inactivated SARS-CoV-2 vaccine or the placebo were administered intramuscularly with 56 a 2- or 4-week interval between the injections. The safety and immunogenicity of the vaccine 57 were evaluated within 28 days. 58

FINDING: 59 In this study, 191 subjects assigned to three doses groups or the ...


Is Smaller Better? Vaccine Targeting Recombinant Receptor-Binding Domain Might Hold The Key For Mass Production Of Effective Prophylactics To Fight The Covid-19 Pandemic, Manish Muhuri, Guangping Gao 2020 University of Massachusetts Medical School

Is Smaller Better? Vaccine Targeting Recombinant Receptor-Binding Domain Might Hold The Key For Mass Production Of Effective Prophylactics To Fight The Covid-19 Pandemic, Manish Muhuri, Guangping Gao

COVID-19 Publications by UMMS Authors

A recent report by Yang et al. published in Nature reported a recombinant vaccine utilizing recombinant receptor-binding domain (RBD) of SARS-CoV-2 Spike Protein.This vaccine candidate successfully induced potent functional antibody responses in the immunized mice, rabbits, and non-human primates. The study highlights the critical role of the immunogenicity of the RBD domain upon SARS-CoV-2 infection and the alternate vaccine designs that could serve as effective prophylactics against the pandemic.


Aci-35 And Aadvac1 Active Immunotherapy As Preventative Treatment Options For Chronic Traumatic Encephalopathy, Emily C. Boehlein 2020 Southeastern University - Lakeland

Aci-35 And Aadvac1 Active Immunotherapy As Preventative Treatment Options For Chronic Traumatic Encephalopathy, Emily C. Boehlein

Selected Honors Theses

One of the most common, as well as one of the most dangerous injuries amongst athletes today is mild traumatic brain injury (mTBI), commonly known as concussion. Aside from physical symptoms such as nausea, dizziness, and headaches; concussions have can have longterm effects on brain physiology. A common neurological disease that can result from multiple concussions is Chronic Traumatic Encephalopathy (CTE), characterized by symptoms such as severe depression, anxiety, confusion, and aggression; amongst others.1 On the cellular level, CTE is classified by a unique pathway that leads to the hyperphosphorylation of tau protein and subsequent clumping of tau-containing neurofibrillary ...


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