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Immunology and Infectious Disease Commons

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The Rational Design, Synthesis, Characterization, And Biological Evaluation Of Cancer-Targeting Immunostimulatory Peptide-Protein Conjugates And Tripeptides, Keith Smith 2018 Seton Hall University

The Rational Design, Synthesis, Characterization, And Biological Evaluation Of Cancer-Targeting Immunostimulatory Peptide-Protein Conjugates And Tripeptides, Keith Smith

Seton Hall University Dissertations and Theses (ETDs)

With the advent of cancer immunotherapy and the rise in applications of synthetic biologics, there has been a steady decline in the incidence of cancer. Despite this trend, there is an anticipated 1.7 million new cancer cases with an estimated 610,000 deaths expected by the end of 2018.2 Therefore, the call for continued efforts in creating more effective treatment options are still in high demand. In this thesis, the rational design of a semi-synthetic cancer-targeting immunostimulatory peptide-protein bioconjugate—using N-succinimidyl carbamate chemistry is described. This bio-orthogonal chemistry approach was used to conjugate the synthetic Pep42, cancer-targeting peptide ...


Bacillus Thuringiensis Cry5b Protein As A New Pan-Hookworm Cure, Yan Hu, Thanh-thanh Nguyen, Alice C. Lee Y, Joseph F. Urban Jr, Melanie M. Miller, Bin Zhan, David Koch, Jason B. Noon, Ricardo Toshio. Fujiwara, Dwight D. Bowman, Gary R. Ostroff, Raffi V. Aroian 2018 University of Massachusetts Medical School

Bacillus Thuringiensis Cry5b Protein As A New Pan-Hookworm Cure, Yan Hu, Thanh-Thanh Nguyen, Alice C. Lee Y, Joseph F. Urban Jr, Melanie M. Miller, Bin Zhan, David Koch, Jason B. Noon, Ricardo Toshio. Fujiwara, Dwight D. Bowman, Gary R. Ostroff, Raffi V. Aroian

Open Access Articles

Hookworms are intestinal nematode parasites that infect nearly half a billion people and are globally one of the most important contributors to iron-deficiency anemia. These parasites have significant impacts in developing children, pregnant women and working adults. Of all the soil-transmitted helminths or nematodes (STNs), hookworms are by far the most important, with disease burdens conservatively estimated at four million DALYs (Disability-Adjusted Life Years) and with productivity losses of up to US$139 billion annually. To date, mainly one drug, albendazole is used for hookworm therapy in mass drug administration, which has on average approximately 80% cure rate that is ...


Resistant Gonorrhoea: East Meets West, Peter A. Rice, Xiao-Hong Su 2018 University of Massachusetts Medical School

Resistant Gonorrhoea: East Meets West, Peter A. Rice, Xiao-Hong Su

Open Access Articles

In 2016 and 2018, two treatment failures of ceftriaxone and azithromycin, used in combination, were reported in the UK in men who contracted gonococcal infections in Asia,1, 2 once again suggesting that antimicrobial resistance of Neisseria gonorrhoeae is spreading. These treatment failures indicate the potentially waning efficacy and usefulness of this combination, which is currently recommended as the first-line therapy. Surveillance of antimicrobial resistance is paramount if resistance patterns of these and other antimicrobials are to be recognised in a timely manner that enables meaningful intervention and prevention of the spread of resistant organisms. Antimicrobial susceptibility testing (phenotyping) for ...


The Role Of Eukaryotic Abc-Transporters In Eliciting Neutrophil Infiltration During Streptococcus Pneumoniae Infection, Andrew Zukauskas 2018 University of Massachusetts Medical School

The Role Of Eukaryotic Abc-Transporters In Eliciting Neutrophil Infiltration During Streptococcus Pneumoniae Infection, Andrew Zukauskas

GSBS Dissertations and Theses

Streptococcus pneumoniae (S. pneumoniae) is a Gram-positive, encapsulated bacterium capable of causing significant morbidity and mortality throughout the world. A hallmark of S. pneumoniae infection is infiltration of neutrophils (PMNs) that assist in controlling the spread infection but may also contribute to pathology. Paradoxically, studies have shown that limiting PMN infiltration into the lumen of the lung during infection actually betters clinical outcome in experimental S. pneumoniae infection. The final step in PMN luminal trafficking is a Hepoxilin A3 (HXA3)-dependent migration across the pulmonary epithelium. HXA3 is a PMN chemoattractant that forms gradients along the polarized epithelial ...


A Recombinant Herpesviral Vector Containing A Near-Full-Length Sivmac239 Genome Produces Siv Particles And Elicits Immune Responses To All Nine Siv Gene Products, Young C. Shin, Georg F. Bischof, William A. Lauer, Lucas Gonzalez-Nieto, Eva G. Rakasz, Gregory M. Hendricks, David I. Watkins, Mauricio A. Martins, Ronald C. Desrosiers 2018 University of Miami

A Recombinant Herpesviral Vector Containing A Near-Full-Length Sivmac239 Genome Produces Siv Particles And Elicits Immune Responses To All Nine Siv Gene Products, Young C. Shin, Georg F. Bischof, William A. Lauer, Lucas Gonzalez-Nieto, Eva G. Rakasz, Gregory M. Hendricks, David I. Watkins, Mauricio A. Martins, Ronald C. Desrosiers

Radiology Publications and Presentations

The properties of the human immunodeficiency virus (HIV) pose serious difficulties for the development of an effective prophylactic vaccine. Here we describe the construction and characterization of recombinant (r), replication-competent forms of rhesus monkey rhadinovirus (RRV), a gamma-2 herpesvirus, containing a near-full-length (nfl) genome of the simian immunodeficiency virus (SIV). A 306-nucleotide deletion in the pol gene rendered this nfl genome replication-incompetent as a consequence of deletion of the active site of the essential reverse transcriptase enzyme. Three variations were constructed to drive expression of the SIV proteins: one with SIV's own promoter region, one with a cytomegalovirus (cmv ...


Fas Ligand Promotes An Inducible Tlr-Dependent Model Of Cutaneous Lupus-Like Inflammation, Purvi Mande, Bahar Zirak, Wei-Che Ko, Keyon Taravati, Karen L. Bride, Tia Bumpus Brodeur, April C. Deng, Karen A. Dresser, Zhaozhao Jiang, Rachel Ettinger, Katherine A. Fitzgerald, Michael D. Rosenblum, John E. Harris, Ann Marshak-Rothstein 2018 University of Massachusetts Medical School

Fas Ligand Promotes An Inducible Tlr-Dependent Model Of Cutaneous Lupus-Like Inflammation, Purvi Mande, Bahar Zirak, Wei-Che Ko, Keyon Taravati, Karen L. Bride, Tia Bumpus Brodeur, April C. Deng, Karen A. Dresser, Zhaozhao Jiang, Rachel Ettinger, Katherine A. Fitzgerald, Michael D. Rosenblum, John E. Harris, Ann Marshak-Rothstein

University of Massachusetts Medical School Faculty Publications

Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, Tlr9-/- autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class II+ cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9. These mice are distinguished by a high frequency of OVA-specific Tbet ...


Avoiding Death Like The Plague: Wound Care In The Roman Army, Gwendolyn E. Dougherty 2018 Nazareth College of Rochester

Avoiding Death Like The Plague: Wound Care In The Roman Army, Gwendolyn E. Dougherty

#History: A Journal of Student Research

At its peak, Roman Empire controlled over two million square miles of territory. To conquer and control that much land, Rome produced a highly skilled army. Casualties and deaths were to be expected, but ancient medical sources about caring for the wounded in the Roman army point to treatments considered advanced for the time period. Galen of Pergamum was an important contributor to this field. The use of food products and natural resources helped combat infections, healing the wounded soldiers and returning them to their military units. This paper identifies and analyzes what those specific products for wound care were ...


Inflammation And Immune Evasion Coexist In Treponema Pallidum-Infected Skin, Rodolfo Trujillo, Jorge Cervantes, Kelly L. Hawley, Adriana R. Cruz, Sankhiros Babapoor, Michael Murphy, Soheil S. Dadras, Juan C. Salazar 2018 Sacred Heart University

Inflammation And Immune Evasion Coexist In Treponema Pallidum-Infected Skin, Rodolfo Trujillo, Jorge Cervantes, Kelly L. Hawley, Adriana R. Cruz, Sankhiros Babapoor, Michael Murphy, Soheil S. Dadras, Juan C. Salazar

Biology Faculty Publications

Syphilis is a systemic, multistage, sexually transmitted infection caused by the highly invasive spirochetal bacterium, Treponema pallidum, subspecies pallidum. In the United States, the annual rate of primary and secondary syphilis (SS) between 2002 and 2016 has increased from 2.1 to 8.7 cases per 100,000.1 Gestational and congenital syphilis cases have also increased in the last few years. There is no evidence of a change in T pallidum susceptibility to penicillin as an explanation for the significant increase in the number of syphilis cases in the United States. It is more likely that changes in risk-taking ...


Quantifying Effects Of Neutrophil Memory On Migration Patterns Using Microfluidic Platforms And Ode Modeling Of The Mechanistic Molecular Pathways, Brittany P. Boribong, Mark J. Lenzi, Mirjam Sarah Kadelka, Stanca Ciupe, Liwu Li, Caroline N. Jonea 2018 Virginia Polytechnic Institute and State University

Quantifying Effects Of Neutrophil Memory On Migration Patterns Using Microfluidic Platforms And Ode Modeling Of The Mechanistic Molecular Pathways, Brittany P. Boribong, Mark J. Lenzi, Mirjam Sarah Kadelka, Stanca Ciupe, Liwu Li, Caroline N. Jonea

Biology and Medicine Through Mathematics Conference

No abstract provided.


The Role Of Outcome Preferences In Optimizing Heterogenous Disease Control Strategies., Evan Milliken 2018 Arizona State University at the Tempe Campus

The Role Of Outcome Preferences In Optimizing Heterogenous Disease Control Strategies., Evan Milliken

Biology and Medicine Through Mathematics Conference

No abstract provided.


Immunohistochemical Expression And Prognostic Value Of Pd-L1 In Extrapulmonary Small Cell Carcinoma: A Single Institution Experience, Mohammed Salhab, Yazan Migdady, Melanie Donahue, Yiqin Xiong, Karen A. Dresser, William Walsh, Benjamin J. Chen, James Liebmann 2018 University of Massachusetts Medical School

Immunohistochemical Expression And Prognostic Value Of Pd-L1 In Extrapulmonary Small Cell Carcinoma: A Single Institution Experience, Mohammed Salhab, Yazan Migdady, Melanie Donahue, Yiqin Xiong, Karen A. Dresser, William Walsh, Benjamin J. Chen, James Liebmann

Open Access Articles

BACKGROUND: Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors.

METHODS: We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material ...


Polymorphic Factor H-Binding Activity Of Cspa Protects Lyme Borreliae From The Host Complement In Feeding Ticks To Facilitate Tick-To-Host Transmission, Thomas Hart, Ngoc Thien Nguyen Thu, Nancy A. Nowak, Fuming Zhang, Robert J. Linhardt, Maria Diuk-Wasser, Sanjay Ram, Peter Kraiczy, Yi-Pin Lin 2018 State University of New York at Albany

Polymorphic Factor H-Binding Activity Of Cspa Protects Lyme Borreliae From The Host Complement In Feeding Ticks To Facilitate Tick-To-Host Transmission, Thomas Hart, Ngoc Thien Nguyen Thu, Nancy A. Nowak, Fuming Zhang, Robert J. Linhardt, Maria Diuk-Wasser, Sanjay Ram, Peter Kraiczy, Yi-Pin Lin

Open Access Articles

Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease, establishes an initial infection in the host's skin following a tick bite, and then disseminates to distant organs, leading to multisystem manifestations. Tick-to-vertebrate host transmission requires that Bbsl survives during blood feeding. Complement is an important innate host defense in blood and interstitial fluid. Bbsl produces a polymorphic surface protein, CspA, that binds to a complement regulator, Factor H (FH) to block complement activation in vitro. However, the role that CspA plays in the Bbsl enzootic cycle remains unclear. In this study, we demonstrated that different CspA variants ...


The Wide Utility Of Rabbits As Models Of Human Diseases, Pedro J. Esteves, Yuxing Chen, Shuying Liu, Shan Lu, Michael Vaine, Shixia Wang, Rose Mage 2018 Universidade do Porto, Portugal

The Wide Utility Of Rabbits As Models Of Human Diseases, Pedro J. Esteves, Yuxing Chen, Shuying Liu, Shan Lu, Michael Vaine, Shixia Wang, Rose Mage

Open Access Articles

Studies using the European rabbit Oryctolagus cuniculus contributed to elucidating numerous fundamental aspects of antibody structure and diversification mechanisms and continue to be valuable for the development and testing of therapeutic humanized polyclonal and monoclonal antibodies. Additionally, during the last two decades, the use of the European rabbit as an animal model has been increasingly extended to many human diseases. This review documents the continuing wide utility of the rabbit as a reliable disease model for development of therapeutics and vaccines and studies of the cellular and molecular mechanisms underlying many human diseases. Examples include syphilis, tuberculosis, HIV-AIDS, acute hepatic ...


Poorly Cytotoxic Terminally Differentiated Cd56(Neg)Cd16(Pos) Nk Cells Accumulate In Kenyan Children With Burkitt Lymphomas, Catherine Forconi, Cormac P. Cosgrove, Pryia Saikumar-Lakshmi, Christina E. Nixon, Joslyn Foley, John Michael Ong'echa, Juliana A. Otieno, Galit Alter, Christian Munz, Ann M. Moormann 2018 University of Massachusetts Medical School

Poorly Cytotoxic Terminally Differentiated Cd56(Neg)Cd16(Pos) Nk Cells Accumulate In Kenyan Children With Burkitt Lymphomas, Catherine Forconi, Cormac P. Cosgrove, Pryia Saikumar-Lakshmi, Christina E. Nixon, Joslyn Foley, John Michael Ong'echa, Juliana A. Otieno, Galit Alter, Christian Munz, Ann M. Moormann

Open Access Articles

Natural killer (NK) cells are critical for restricting viral infections and mediating tumor immunosurveillance. Epstein-Barr virus (EBV) and Plasmodium falciparum malaria are known risk factors for endemic Burkitt lymphoma (eBL), the most common childhood cancer in equatorial Africa. To date, the composition and function of NK cells have not been evaluated in eBL etiology or pathogenesis. Therefore, using multiparameter flow cytometry and in vitro killing assays, we compared NK cells from healthy children and children diagnosed with eBL in Kenya. We defined 5 subsets based on CD56 and CD16 expression, including CD56(neg)CD16(pos) We found that licensed and ...


Mycobacterium Tuberculosis-Specific Cd4+ And Cd8+ T Cells Differ In Their Capacity To Recognize Infected Macrophages, Jason D. Yang, Daniel Mott, Rujapak Sutiwisesak, Yu-Jung Lu, Fiona Raso, Britni Stowell, Greg Hunter Babunovic, Jinhee Lee, Stephen M. Carpenter, Sing Sing Way, Sarah M. Fortune, Samuel M. Behar 2018 University of Massachusetts Medical School

Mycobacterium Tuberculosis-Specific Cd4+ And Cd8+ T Cells Differ In Their Capacity To Recognize Infected Macrophages, Jason D. Yang, Daniel Mott, Rujapak Sutiwisesak, Yu-Jung Lu, Fiona Raso, Britni Stowell, Greg Hunter Babunovic, Jinhee Lee, Stephen M. Carpenter, Sing Sing Way, Sarah M. Fortune, Samuel M. Behar

Open Access Articles

Containment of Mycobacterium tuberculosis (Mtb) infection requires T cell recognition of infected macrophages. Mtb has evolved to tolerate, evade, and subvert host immunity. Despite a vigorous and sustained CD8+ T cell response during Mtb infection, CD8+ T cells make limited contribution to protection. Here, we ask whether the ability of Mtb-specific T cells to restrict Mtb growth is related to their capacity to recognize Mtb-infected macrophages. We derived CD8+ T cell lines that recognized the Mtb immunodominant epitope TB10.44-11 and compared them to CD4+ T cell lines that recognized Ag85b240-254 or ESAT63-17. While the CD4+ T cells recognized Mtb-infected ...


Disruption Of Tblpn Expression In T. Brucei By Rna Interference, Matthew Serbonich 2018 The College at Brockport

Disruption Of Tblpn Expression In T. Brucei By Rna Interference, Matthew Serbonich

Senior Honors Theses

Trypanosoma brucei, the causative agent of human African trypanosomiasis, also known as African sleeping sickness, expresses a protein known as TbLpn which plays a critical role in arginine methylation and phospholipid synthesis within T. brucei. In order to determine the effect and potential medical benefits of downregulated TbLpn expression in T. brucei, RNA interference was used by transfecting T. brucei with plasmid DNA through electroporation. After conducting this experimental protocol, T. brucei was unable to be grown successfully in media following transfection and the effect of downregulated TbLpn in T. brucei requires further investigation in order to determine its potential ...


Negative Regulators Of Colonic Peripheral Regulatory T Cell Development, Teresa Lei Ai 2018 Washington University in St. Louis

Negative Regulators Of Colonic Peripheral Regulatory T Cell Development, Teresa Lei Ai

Arts & Sciences Electronic Theses and Dissertations

Peripheral Treg cells (pTreg cells) maintain immune homeostasis at mucosal interfaces, where they can develop upon activation of naïve CD4+ T cells by bacteria antigen. However, the cellular and molecular requirements that govern their differentiation in inflamed and homeostatic contexts require further elucidation. To circumvent uncertainties in existing methods of distinguishing pTreg cells from thymic Treg cells (tTreg cells), we analyzed monoclonal cell populations of CT2 and CT6 transgenic (Tg) cells that develop into pTreg cells in response to different species of endogenously presented Helicobacter antigen. In our comprehensive assessment of multiple intestinal inflammatory models, including infections and physical injury ...


Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer 2018 Washington University in St. Louis

Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer

Arts & Sciences Electronic Theses and Dissertations

Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are ...


Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori McGinnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison 2018 Sigmovir Biosystems Inc.

Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori Mcginnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison

Open Access Articles

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization is an option to increase maternal antibody levels and protect infants from infection. Here we assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. VLP vaccines containing RSV F and G proteins strongly boost pre-existing RSV immunity in dams preventing their perinatal drop in immunity. Boosting is stronger for the pre-F VLP than for the post-F VLP or ...


P38b And Jak-Stat Signaling Protect Against Invertebrate Iridescent Virus 6 Infection In Drosophila, Cara C. West, Neal S. Silverman 2018 University of Massachusetts Medical School

P38b And Jak-Stat Signaling Protect Against Invertebrate Iridescent Virus 6 Infection In Drosophila, Cara C. West, Neal S. Silverman

Open Access Articles

The fruit fly Drosophila melanogaster is a powerful model system for the study of innate immunity in vector insects as well as mammals. For vector insects, it is particularly important to understand all aspects of their antiviral immune defenses, which could eventually be harnessed to control the transmission of human pathogenic viruses. The immune responses controlling RNA viruses in insects have been extensively studied, but the response to DNA virus infections is poorly characterized. Here, we report that infection of Drosophila with the DNA virus Invertebrate iridescent Virus 6 (IIV-6) triggers JAK-STAT signaling and the robust expression of the Turandots ...


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