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Immunology and Infectious Disease

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Lenalidomide Enhances Cd23car T Cell Therapy In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio Jul 2022

Lenalidomide Enhances Cd23car T Cell Therapy In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells. We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide maintained the in vitro effector functions of CD23.CAR+ T cells effector functions in terms of antigen-specific cytotoxicity, cytokine release …


Reshaping The Tumor Microenvironment With Oncolytic Viruses, Positive Regulation Of The Immune Synapse, And Blockade Of The Immunosuppressive Oncometabolic Circuitry, Teresa T Nguyen, Dong Ho Shin, Sagar Sohoni, Sanjay K Singh, Yisel Rivera-Molina, Hong Jiang, Xuejun Fan, Joy Gumin, Frederick F Lang, Christopher Alvarez-Breckenridge, Filipa Godoy-Vitorino, Lisha Zhu, W Jim Zheng, Lijie Zhai, Erik Ladomersky, Kristen L Lauing, Marta M Alonso, Derek A Wainwright, Candelaria Gomez-Manzano, Juan Fueyo Jul 2022

Reshaping The Tumor Microenvironment With Oncolytic Viruses, Positive Regulation Of The Immune Synapse, And Blockade Of The Immunosuppressive Oncometabolic Circuitry, Teresa T Nguyen, Dong Ho Shin, Sagar Sohoni, Sanjay K Singh, Yisel Rivera-Molina, Hong Jiang, Xuejun Fan, Joy Gumin, Frederick F Lang, Christopher Alvarez-Breckenridge, Filipa Godoy-Vitorino, Lisha Zhu, W Jim Zheng, Lijie Zhai, Erik Ladomersky, Kristen L Lauing, Marta M Alonso, Derek A Wainwright, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Background: Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms underlying the immunosuppressive tumor microenvironment optimizes viroimmunotherapy.

Methods: We used RNA-seq analyses to analyze the transcriptome, and validated the results using Q-PCR, flow cytometry, and immunofluorescence. Viral activity was analyzed by replication assays and viral titration. Kyn and Trp metabolite levels were quantified using liquid chromatography-mass spectrometry. Aryl hydrocarbon receptor (AhR) activation …


Pirtobrutinib Inhibits Wild-Type And Mutant Bruton’S Tyrosine Kinase-Mediated Signaling In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio Jul 2022

Pirtobrutinib Inhibits Wild-Type And Mutant Bruton’S Tyrosine Kinase-Mediated Signaling In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells.

We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide preserves CD23.CAR T cells in vitro effector functions in terms of antigen-specific cytotoxicity, cytokine release and proliferation. Overall, lenalidomide …


Trends In Utilization Of Human Papillomavirus Vaccines And The Incidence Of Malignant Cervical Cancer In The U.S. Population: A Secondary Analysis, Myah Luna, Soumya Upadhyay Jun 2022

Trends In Utilization Of Human Papillomavirus Vaccines And The Incidence Of Malignant Cervical Cancer In The U.S. Population: A Secondary Analysis, Myah Luna, Soumya Upadhyay

Healthcare Administration and Policy Faculty Research

Background: Human papillomavirus (HPV) is a sexually transmitted infection, and HPV types 16 and 18 are responsible for approximately 66% of all U.S. cervical cancer cases in women. The quadrivalent HPV vaccine was licensed in mid-2006, and it was designed to target and protect against HPV types 6, 11, 16, and 18. The aim of this study is to examine the utilization rate of the HPV vaccine, and the trends and incidence rate of malignant cervical cancer across the United States. Methods: This study utilized data from Surveillance, Epidemiology, and End Results (SEER) and the National Immunization Survey's (NIS) teenage …


Seroprevalence Of Sars-Cov-2 Antibodies, The Gut Microbiome, And Peripherally Circulating Cytokines In Pregnant Hispanic Females, Tina Susanna Mutka Jun 2022

Seroprevalence Of Sars-Cov-2 Antibodies, The Gut Microbiome, And Peripherally Circulating Cytokines In Pregnant Hispanic Females, Tina Susanna Mutka

USF Tampa Graduate Theses and Dissertations

Pregnant Hispanic females have been disproportionately impacted by SARS-CoV-2 andhave experienced high rates of asymptomatic or mildly symptomatic, unrecognized infection. Acute SARS-CoV-2 infection has been associated with gut microbiome changes and altered peripherally circulating cytokine levels in symptomatic, non-pregnant individuals.

This study investigated the seroprevalence of anti-SARS-CoV-2 IgG antibodies in a sample of pregnant Hispanic females (n = 197). A sub-sample of SARS-CoV-2 seropositive and seronegative pregnant Hispanic females were followed across pregnancy and their bacterial gut microbiome was characterized, and cytokine levels measured to investigate relationships between SARS-CoV-2 serostatus, the gut microbiome, and peripherally circulating cytokine levels across pregnancy. …


Robust Network Stability Of Mosquitoes And Human Pathogens Of Medical Importance, Donald A. Yee, Catherine Dean Bermond, Limarie J. Reyes-Torres, Nicole S. Fijman, Nicole A. Scavo, Joseph Nelsen, Susan H. Yee Jun 2022

Robust Network Stability Of Mosquitoes And Human Pathogens Of Medical Importance, Donald A. Yee, Catherine Dean Bermond, Limarie J. Reyes-Torres, Nicole S. Fijman, Nicole A. Scavo, Joseph Nelsen, Susan H. Yee

Faculty Publications

Background: The exact number of mosquito species relevant to human health is unknown, posing challenges in understanding the scope and breadth of vector–pathogen relationships, and how resilient mosquito vector–pathogen networks are to targeted eradication of vectors.

Methods: We performed an extensive literature survey to determine the associations between mosquito species and their associated pathogens of human medical importance. For each vector–pathogen association, we then determined the strength of the associations (i.e., natural infection, lab infection, lab dissemination, lab transmission, known vector). A network analysis was used to identify relationships among all pathogens and vectors. Finally, we examined how …


Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto Jun 2022

Neoadjuvant Immunotherapy Across Cancers: Meeting Report From The Immunotherapy Bridge-December 1st–2nd, 2021, Elizabeth M Burton, Rodabe N Amaria, Tina Cascone, Myriam Chalabi, Neil D Gross, Elizabeth A Mittendorf, Richard A Scolyer, Padmanee Sharma, Paolo A Ascierto

Faculty, Staff and Student Publications

After the success of immunotherapy in the treatment of advanced metastatic cancer, further evaluation in earlier settings, including high-risk, surgically-resectable disease is underway. Potential benefits of a neoadjuvant immunotherapeutic approach include presurgical tumor shrinkage, reduced surgical morbidity, early eradication of micrometastases and prevention of distant disease, and greater antigen-specific T cell response. For some cancers, pathologic response has been established as a surrogate measure for long-term outcomes, therefore offering the ability for early and objective assessment of treatment efficacy and the potential to inform and personalize adjuvant treatment clinical decision-making. Leveraging the neoadjuvant treatment setting offers the ability to deeply …


Characterizing Endogenous Dicer Products To Unravel Novel Rnai Biogenesis Pathways, Jacob Oche Peter Jun 2022

Characterizing Endogenous Dicer Products To Unravel Novel Rnai Biogenesis Pathways, Jacob Oche Peter

Dissertations

ABSTRACT

RNA interference (RNAi) is a pervasive gene regulatory mechanism in eukaryotes based on the action of multiple classes of small RNA (sRNA). Exploiting RNAi pathways in non-model systems have great potential for creating potent RNAi technologies. Here, we accessed RNAi-mediated control of gene expression in the two-spotted spider mite, Tetranychus urticae (T. urticae) using engineered dsRNA designed to modulate the host RNAi pathway and increase RNAi efficacy. Analysis of Dicer (Dcr) generated fragments revealed how exogenous RNAs access the host RNAi pathway in this animal, opening avenues for designing RNAi technology for their control. Further, some organisms …


In Sickness And In Health: Parasites Of Stranded Pacific Harbor Seals (Phoca Vitulina Richardii) In Northern Oregon And Southern Washington, Cecily Douglas Bronson Jun 2022

In Sickness And In Health: Parasites Of Stranded Pacific Harbor Seals (Phoca Vitulina Richardii) In Northern Oregon And Southern Washington, Cecily Douglas Bronson

Dissertations and Theses

Parasites have the capability to infect virtually every living organism on the planet and have adapted to infiltrate every trophic level. Many species have complex indirect life cycles and rely upon hosts at different levels of the food web for growth and reproduction. In the marine environment, having a high level of parasite diversity is thought to indicate a more stable ecosystem than an environment with low parasite diversity. As one of the top predators in their environment and because of their amphibious behaviors, pinnipeds (seals and sea lions) are exposed to a wide variety of parasites, making them ideal …


Systemic Ablation Of Camkk2 Impairs Metastatic Colonization And Improves Insulin Sensitivity In Tramp Mice: Evidence For Cancer Cell-Extrinsic Camkk2 Functions In Prostate Cancer, Thomas L Pulliam, Dominik Awad, Jenny J Han, Mollianne M Murray, Jeffrey J Ackroyd, Pavithr Goli, Jonathan S Oakhill, John W Scott, Michael M Ittmann, Daniel E Frigo Jun 2022

Systemic Ablation Of Camkk2 Impairs Metastatic Colonization And Improves Insulin Sensitivity In Tramp Mice: Evidence For Cancer Cell-Extrinsic Camkk2 Functions In Prostate Cancer, Thomas L Pulliam, Dominik Awad, Jenny J Han, Mollianne M Murray, Jeffrey J Ackroyd, Pavithr Goli, Jonathan S Oakhill, John W Scott, Michael M Ittmann, Daniel E Frigo

Faculty, Staff and Students Publications

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2's effects on whole-body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of


Borders: A Story Of Political Imagination, Miriam Ticktin Jun 2022

Borders: A Story Of Political Imagination, Miriam Ticktin

Publications and Research

This article traces three different political imaginaries about borders, suggesting that the dominant imaginary—the one of border walls, driven by a fear of invasion—is only one way to live in the world. The goal is to make space in our political imaginations to rethink how we live together, including thinking beyond nation-states as containers that keep people in or out. By first showing how the vision of invasion is built and maintained with intersecting transnational technologies and ideologies, I open the way to thinking otherwise. Second, I trace the counterpolitics of borders developed by artists and activists, resisting borders and …


Maternal Responses In The Face Of Infection Risk, Patricia C. Lopes, Brenna M. G. Gormally, Aubrey Emmi, Delilah Schuerman, Chathuni Liyanage, Ursula K. Beattie, L. Michael Romero Jun 2022

Maternal Responses In The Face Of Infection Risk, Patricia C. Lopes, Brenna M. G. Gormally, Aubrey Emmi, Delilah Schuerman, Chathuni Liyanage, Ursula K. Beattie, L. Michael Romero

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When animals are sick, their physiology and behavior change in ways that can impact their offspring. Research is emerging showing that infection risk alone can also modify the physiology and behavior of healthy animals. If physiological responses to environments with high infection risk take place during reproduction, it is possible that they lead to maternal effects. Understanding whether and how high infection risk triggers maternal effects is important to elucidate how the impacts of infectious agents extend beyond infected individuals and how, in this way, they are even stronger evolutionary forces than already considered. Here, to evaluate the effects of …


Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty Jun 2022

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …


Distinct Immune Gene Programs Associated With Host Tumor Immunity, Neoadjuvant Chemotherapy, And Chemoimmunotherapy In Resectable Nsclc, Pedro Rocha, Jiexin Zhang, Raquel Laza-Briviesca, Alberto Cruz-Bermúdez, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridon, Katsuhiro Yoshimura, Carmen Behrens, Wei Lu, Ximing Tang, Apar Pataer, Edwin R Parra, Cara Haymaker, Junya Fujimoto, Stephen G Swisher, John V Heymach, Don L Gibbons, J Jack Lee, Boris Sepesi, Tina Cascone, Luisa M Solis, Mariano Provencio, Ignacio I Wistuba, Humam Kadara Jun 2022

Distinct Immune Gene Programs Associated With Host Tumor Immunity, Neoadjuvant Chemotherapy, And Chemoimmunotherapy In Resectable Nsclc, Pedro Rocha, Jiexin Zhang, Raquel Laza-Briviesca, Alberto Cruz-Bermúdez, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridon, Katsuhiro Yoshimura, Carmen Behrens, Wei Lu, Ximing Tang, Apar Pataer, Edwin R Parra, Cara Haymaker, Junya Fujimoto, Stephen G Swisher, John V Heymach, Don L Gibbons, J Jack Lee, Boris Sepesi, Tina Cascone, Luisa M Solis, Mariano Provencio, Ignacio I Wistuba, Humam Kadara

Faculty, Staff and Student Publications

Purpose: Our understanding of the immunopathology of resectable non-small cell lung cancer (NSCLC) is still limited. Here, we explore immune programs that inform of tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in localized NSCLC.

Experimental design: Targeted immune gene sequencing using the HTG Precision Immuno-Oncology panel was performed in localized NSCLCs from three cohorts based on treatment: naïve (n = 190), neoadjuvant chemotherapy (n = 38), and neoadjuvant chemoimmunotherapy (n = 21). Tumor immune microenvironment (TIME) phenotypes were based on the location of CD8+ T cells (inflamed, cold, excluded), tumoral PD-L1 expression (<1% and ≥1%), and tumor-infiltrating lymphocytes (TIL). Immune programs and signatures were statistically analyzed on the basis of tumoral PD-L1 expression, immune phenotypes, and pathologic response and were cross-compared across the three cohorts.

Results: PD-L1-positive tumors exhibited increased …


Comprehensive Characterization Of Tumor Immune Landscape Following Oncolytic Virotherapy By Single-Cell Rna Sequencing, Divya Ravirala, Guangsheng Pei, Zhongming Zhao, Xiaoliu Zhang Jun 2022

Comprehensive Characterization Of Tumor Immune Landscape Following Oncolytic Virotherapy By Single-Cell Rna Sequencing, Divya Ravirala, Guangsheng Pei, Zhongming Zhao, Xiaoliu Zhang

Faculty, Staff and Student Publications

An important mechanism of oncolytic virotherapy in ameliorating cancer immunotherapy is by inducing significant changes in the immune landscape in the tumor microenvironment (TME). Despite this notion and the potential therapeutic implications, a comprehensive analysis of the immune changes in carcinomas induced by virotherapy has not yet been elucidated. We conducted single-cell RNA sequencing analysis on carcinomas treated with an HSV-2-based oncolytic virus to characterize the immunogenic changes in the TME. We specifically analyzed and compared the immune cell composition between viral treated and untreated tumors. We also applied CellChat to analyze the complex interactions among the infiltrated immune cells. …


Factors Affecting The Antibacterial Activity Of Cefiderocol On Klebsiella Pneumoniae With Diverse Characteristics, Lana Jamal Rashed Daoud Jun 2022

Factors Affecting The Antibacterial Activity Of Cefiderocol On Klebsiella Pneumoniae With Diverse Characteristics, Lana Jamal Rashed Daoud

Theses

Antimicrobial resistance (AMR) is a growing serious threat that poses a burden on the healthcare system. Spread of AMR bacteria limits treatment options; thus, new antimicrobial agents are required. Cefiderocol (CFDC) is a novel siderophore cephalosporin, approved by the FDA in 2019 for use in treating infections caused by multi-drug resistant (MDR) pathogens; but it is not yet in clinical use in the UAE. CFDC is equipped with stabilizers against β-lactamases as well as a siderophore side chain that allows it to penetrate the outer membrane of bacteria through the iron uptake pathways. The aim of this study is to …


Genomic Insights Into Mechanisms Of Microbial Evolution And Evolution-Inspired Strategies To Combat Pathogen Diversity, Saymon Akther Jun 2022

Genomic Insights Into Mechanisms Of Microbial Evolution And Evolution-Inspired Strategies To Combat Pathogen Diversity, Saymon Akther

Dissertations, Theses, and Capstone Projects

We live in an era of emerging infectious diseases that are increasingly common, rapidly spreading, and gravely devastating. Lyme disease, caused by bacteria belonging to the genus Borreliella, is rapidly rising in the Northern Hemisphere because of geographic range expansion of both the tick vectors and the pathogens. Evolutionary comparative analysis of Borreliella genomes is a key to understanding the phylogeographic history and mechanisms of their global diversification. Moreover, genomic variations in Borreliella associated with human pathogenicity, e.g., at loci encoding cell-surface antigens interacting with the vertebrate hosts, have not been fully identified. Similarly, the ongoing COVID-19 pandemic, caused …


Repeated Low-Level Blast Induces Chronic Neuroinflammation And Neurobehavioral Changes In Rat Models, Arun Reddy Ravula May 2022

Repeated Low-Level Blast Induces Chronic Neuroinflammation And Neurobehavioral Changes In Rat Models, Arun Reddy Ravula

Dissertations

Blast-induced neurotrauma (bTBI) is a signature medical concern for military personnel when they are exposed to explosions in active combat zones. However, soldiers as well as law enforcement personnel are also repeatedly exposed to low-level blasts during training sessions with heavy weaponries as part of combat readiness. Service personnel who sustain brain injuries from repeated low-level blasts (rLLBs) do not display overt pathological symptoms immediately but rather develop cognitive impairments, attention deficits, anxiety, and sleep disturbances over time. An improved rat model of rLLB was developed in this thesis by applying controlled low-level blast pressures (10 psi) repeated five times …


Female Presence Does Not Increase Testosterone But Still Ameliorates Sickness Behaviours In Male Japanese Quail, Brenna M. G. Gormally, Kaelyn Bridgette, Aubrey Emmi, Delilah Schuerman, Patricia C. Lopes May 2022

Female Presence Does Not Increase Testosterone But Still Ameliorates Sickness Behaviours In Male Japanese Quail, Brenna M. G. Gormally, Kaelyn Bridgette, Aubrey Emmi, Delilah Schuerman, Patricia C. Lopes

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Infections can dramatically modify animal behaviour. The extent of these changes depends on an animal's environment. It has been proposed that testosterone modulates the suppression of behavioural symptoms of sickness under certain reproductive contexts. To further understand the role played by testosterone in modulating sickness behaviours under reproductive contexts, we studied a species, the Japanese quail, in which female exposure rapidly decreases circulating testosterone in males. Males received either an immune challenge (lipopolysaccharide – LPS) or a control injection and their behaviours, mass change and testosterone levels were quantified in the presence or absence of a female. Both the presence …


Anti-Amyloid Chimeric Antigen Receptor Macrophages For Alzheimer's Disease Immunotherapy, Qiuyun Pan May 2022

Anti-Amyloid Chimeric Antigen Receptor Macrophages For Alzheimer's Disease Immunotherapy, Qiuyun Pan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Alzheimer’s disease is the most common cause of dementia. None of the available drugs can cure the disease. Chimeric Antigen Receptor (CAR) macrophages, because of their phagocytic activity, have potential as a cellular treatment for amyloid aggregation. In this study, we generated an anti-amyloid CAR hematopoietic progenitor cell line. By inducing the progenitor cell line to differentiate into macrophages, we show that the anti-amyloid CAR-Macrophage has enhanced specific phagocytic activity towards amyloid in in vitro experiments. In addition, in ex vivo experiments, anti-amyloid CAR significantly reduces the plaque load on brain slice from APP/PS1 mice when compared to a non-targeted …


Integrative Genomic Analysis Reveals Low T-Cell Infiltration As The Primary Feature Of Tobacco Use In Hpv-Positive Oropharyngeal Cancer, Benjamin M Wahle, Paul Zolkind, Ricardo J Ramirez, Zachary L Skidmore, Sydney R Anderson, Angela Mazul, D Neil Hayes, Vlad C Sandulache, Wade L Thorstad, Douglas Adkins, Obi L Griffith, Malachi Griffith, Jose P Zevallos May 2022

Integrative Genomic Analysis Reveals Low T-Cell Infiltration As The Primary Feature Of Tobacco Use In Hpv-Positive Oropharyngeal Cancer, Benjamin M Wahle, Paul Zolkind, Ricardo J Ramirez, Zachary L Skidmore, Sydney R Anderson, Angela Mazul, D Neil Hayes, Vlad C Sandulache, Wade L Thorstad, Douglas Adkins, Obi L Griffith, Malachi Griffith, Jose P Zevallos

Faculty, Staff and Students Publications

Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use through whole exome sequencing, mRNA hybridization, and immunohistochemical staining in 47 HPV(+) OPSCC tumors. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T > C substitutions and a lower proportion of expected mutational signatures, but not with …


Mathematical Model Of Immune-Inflammatory Response In Covid-19 Patients, Quiyana M. Murphy May 2022

Mathematical Model Of Immune-Inflammatory Response In Covid-19 Patients, Quiyana M. Murphy

Biology and Medicine Through Mathematics Conference

No abstract provided.


Evaluating The Practical Identifiability Of A Malaria Model To Assess Conversion To Transmissible Stages, Anthony Raymond Krueger, Damie Pak, Megan Greischar, Lauren Childs May 2022

Evaluating The Practical Identifiability Of A Malaria Model To Assess Conversion To Transmissible Stages, Anthony Raymond Krueger, Damie Pak, Megan Greischar, Lauren Childs

Biology and Medicine Through Mathematics Conference

No abstract provided.


Microbial Experience Increases Cytotoxicity Of Tumor-Infiltrating Cd8+ T Cells And Controls Tumor Growth, Nicholas Aaron Bunda May 2022

Microbial Experience Increases Cytotoxicity Of Tumor-Infiltrating Cd8+ T Cells And Controls Tumor Growth, Nicholas Aaron Bunda

Masters Theses

Cancer immunotherapy research is traditionally conducted with specific pathogen-free (SPF) mice, which most accurately mimic the immune system of a human newborn. This makes translational research challenging, as this mouse model is not an accurate reflection of the adult patients who ultimately receive newly developed treatments. It is necessary to further develop a mouse model that bridges this gap and increases translatability of current cancer immunotherapy research.

By cohousing specific pathogen-free mice with regular pet store (PS) mice, we have generated a cohoused (CoH) mouse that reflects the microbial experience of an adult human immune system. We investigated antigen experience, …


Contributions Of Vibrational Spectroscopy To Virology: A Review, Iqra Chaudhary, Naomi Jackson, Denise Denning, Luke O'Neill, Hugh Byrne May 2022

Contributions Of Vibrational Spectroscopy To Virology: A Review, Iqra Chaudhary, Naomi Jackson, Denise Denning, Luke O'Neill, Hugh Byrne

Articles

Vibrational spectroscopic techniques, both infrared absorption and Raman scattering, are high precision, label free analytical techniques which have found applications in fields as diverse as analytical chemistry, pharmacology, forensics and archeometrics and, in recent times, have attracted increasing attention for biomedical applications. As analytical techniques, they have been applied to the characterisation of viruses as early as the 1970s, and, in the context of the coronavirus disease 2019 (COVID-19) pandemic, have been explored in response to the World Health Organisation as novel methodologies to aid in the global efforts to implement and improve rapid screening of viral infection. This review …


Cellular Automata: The Mathematical Theory Behind The Spread Of Covid-19 And Prediction Of Future Spread, Alison Drumheller May 2022

Cellular Automata: The Mathematical Theory Behind The Spread Of Covid-19 And Prediction Of Future Spread, Alison Drumheller

Undergraduate Theses and Capstone Projects

This thesis seeks to analyze the spread of the original COVID-19 strain and develop a mathematical model to predict the chances of being infected by this disease using a number of variables. This model is based on the mathematical theory of cellular automata, otherwise known as the theory of spread. The research uses real world data of COVID-19 which includes infection rate, death rate, vaccination rate, use of masks, and transmission rates. By using cellular automata, we predict that the more preventative measures an individual puts in place for themselves, the less likely they are to be infected by the …


Fine-Mapping Of Human Antibody Specificity In Response To Natural Chlamydia Trachomatis Infection Utilized To Inform Vaccines Against Adhesion Factors, Amanda L. Collar May 2022

Fine-Mapping Of Human Antibody Specificity In Response To Natural Chlamydia Trachomatis Infection Utilized To Inform Vaccines Against Adhesion Factors, Amanda L. Collar

Biomedical Sciences ETDs

Chlamydia trachomatis (Ct) is the causative pathogen for the most common bacterial sexually transmitted infection worldwide and can cause serious medical consequences in women, including pelvic inflammatory disease, ectopic pregnancy, and infertility. For these reasons, a Ct vaccine is urgently needed, yet, its development remains a significant challenge. One barrier to producing a Ct vaccine is the gap in knowledge of protective immune responses for Ct infection, including the role that antibodies may play. Therefore, I aimed to characterize the human antibody response to natural urogenital Ct infection in women using Deep Sequence-Coupled Biopanning. Further, I leveraged these findings to …


Functional Comparison Of Raw 264.7 Cells And Murine Bone Marrow-Derived Macrophages (Bmdm), Quinn Harker May 2022

Functional Comparison Of Raw 264.7 Cells And Murine Bone Marrow-Derived Macrophages (Bmdm), Quinn Harker

Undergraduate Theses and Capstone Projects

RAW 264.7 cells are an immortalized line of mouse cells that are commonly used in immunological research. They will be used to compare against murine bone marrow-derived macrophages (BMDM) to see if the two lines of cells are experimentally comparable in basic inflammatory testing. A standard method of measuring cell activity is through the analysis of nitric oxide production, which can be accomplished using a Griess reaction. Cell counts will be standardized to account for differing growth rates between the two cell lines. A similar output of nitric oxide concentration as an indicator of cellular activity between the RAW 264.7 …


Heterogeneity Of Gene Expression In Peanut-Allergic Cells May Be Related To Differing Cell Subpopulations, Sophia R. Tekorius May 2022

Heterogeneity Of Gene Expression In Peanut-Allergic Cells May Be Related To Differing Cell Subpopulations, Sophia R. Tekorius

Honors Projects

Peanut allergies can have severe and life-threatening complications. By understanding the biology of individuals struggling with this disease, better treatments can be developed. This project explores the possibility of two phenotypically distinct cell types within CD154+ cell types in patients with peanut allergy. Previous studies show that there is a Th2 cell subpopulation associated with allergies, and within effector CD4+ memory populations two distinct phenotypes have been found. This project expands upon this research at the genetic level and through bioinformatic analyses, including the production of heatmaps, the project has found evidence for differing gene expression in two cell subpopulations. …


The Role Of Calprotectin In T-Lymphocyte Driven Inflammation In A Mouse Model Of Psychological Trauma, Cassandra Moshfegh May 2022

The Role Of Calprotectin In T-Lymphocyte Driven Inflammation In A Mouse Model Of Psychological Trauma, Cassandra Moshfegh

Theses & Dissertations

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that affects nearly 45 million Americans. This mental disorder is characterized by behavioral symptoms such as learned helplessness, hyperarousal, withdrawal, and flashbacks. The deleterious effects of PTSD are far-reaching and go beyond behavioral dysfunction, as these individuals are at a three-fold higher risk of comorbid inflammatory diseases. Autonomic, metabolic, and cardiovascular diseases plague these individuals later in their lifetime, however, the mechanistic link connecting psychological trauma to this systemic peripheral immunological dysfunction remains elusive. T-lymphocyte-induced inflammation plays a significant role in all these disease pathologies. Previous work from our laboratory demonstrated …