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Articles 1 - 30 of 135
Full-Text Articles in Virus Diseases
Testing Elicitors Of Homologous Jadr2 Proteins To Regulate Natural Product Production, Carzon J. Williams, Emilee A. Patterson, Allison S. Walker
Testing Elicitors Of Homologous Jadr2 Proteins To Regulate Natural Product Production, Carzon J. Williams, Emilee A. Patterson, Allison S. Walker
SPARK Symposium Presentations
The growing threat of antimicrobial resistance (AMR) has and will contribute to global economic and public health concerns in the foreseeable future leading into 2050. As mortality rates derived from AMR are projected to reach 10 million if no viable solution is found to combat it through hastened drug discovery. The use of natural products to mitigate AMRs effects is viable as more than 50% of FDA approved drugs are natural products. These natural products are synthesized by biosynthetic gene clusters (BGC), found in bacteria with a regulatory protein not allowing transcription until unbound . Current methods of eliciting the …
Mechanisms Of Binding And Immune Escape Resistance For Broadly Neutralizing Antibodies Targeting Distinct Conserved Sars-Cov-2 Spike Epitopes: A Hierarchical Approach Integrating Mutational Profiling And Energy Landscape Analysis, Mohammed Alshahrani, Will Gatlin, Max Ludwick, Lucas Turano, Brandon Foley, Gennady M. Verkhivker
Mechanisms Of Binding And Immune Escape Resistance For Broadly Neutralizing Antibodies Targeting Distinct Conserved Sars-Cov-2 Spike Epitopes: A Hierarchical Approach Integrating Mutational Profiling And Energy Landscape Analysis, Mohammed Alshahrani, Will Gatlin, Max Ludwick, Lucas Turano, Brandon Foley, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
The continued evolution of SARS-CoV-2 has enabled an escape from most monoclonal antibodies, yet a subset of broadly neutralizing antibodies targeting three newly identified super-conserved RBD epitopes—SCORE-A, SCORE-B, and SCORE-C—retains remarkable activity against even the most recent JN.1-derived sublineages. Here, we employed an integrated computational framework combining conformational dynamics, mutational scanning, MM-GBSA binding energetics, and frustration profiling to dissect the molecular mechanisms by which XGI antibodies achieve broad neutralization and resistance to immune escape. Structural analysis revealed that all three SCORE epitopes share a common architecture: a highly conserved, minimally frustrated core that provides stable anchoring, flanked by peripheral regions …
Modulation Of Prussian Blue Redox Signaling By Molecular Imprinting For Reagent-Free Electrochemical Detection Of Emtricitabine, Abdellatif Ait Lahcen, Gymama Slaughter
Modulation Of Prussian Blue Redox Signaling By Molecular Imprinting For Reagent-Free Electrochemical Detection Of Emtricitabine, Abdellatif Ait Lahcen, Gymama Slaughter
Center for Bioelectronics Publications
Reagent-free electrochemical sensors offer significant benefits for rapid, affordable point-of-care drug testing. In this study, we introduce a novel, reagent-free electrochemical sensor based on a molecularly imprinted polymer (MIP) specifically designed for the selective detection of Emtricitabine (FTC), a common antiretroviral used in HIV therapy. The sensor uses laser-induced graphene (LIG) electrodes, renowned for their high conductivity and porosity, ideal for electrochemical sensing. To enable reagent-free operation, the LIG surface was electrochemically coated with Prussian Blue, serving as a redox-active layer. Next, an MIP-PPy film was electropolymerized onto the Prussian Blue surface in the presence of FTC as a template, …
Long Covid Incidence Across Sars-Cov-2 Lineages And Identification Of Conserved Spike Targets For Multivalent Vaccines, Grace J. Kim, Md Ashad Alam, Judy S. Crabtree, Rebecca Rose, Susanna L. Lamers, San Chu, Ronald Horswell, Daniel Fort, Lucio Miele
Long Covid Incidence Across Sars-Cov-2 Lineages And Identification Of Conserved Spike Targets For Multivalent Vaccines, Grace J. Kim, Md Ashad Alam, Judy S. Crabtree, Rebecca Rose, Susanna L. Lamers, San Chu, Ronald Horswell, Daniel Fort, Lucio Miele
School of Graduate Studies Faculty Publications
Background: Long COVID remains poorly characterized at the genomic level. The primary aim of this study was to examine the relationship between viral sequences and the incidence of Long COVID at a tertiary care center in Louisiana between April 2020 and December 2022. A secondary aim was analysis of the Spike protein to identify conserved regions for multivalent vaccine targets. Method: To estimate Long COVID incidence across variants, we linked 4,789 SARS-CoV-2 sequences to 3,090 de-identified patient electronic health record information. The base population was defined as any patient with an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) …
Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025, Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Tamara T. Bradford, Et Al
Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025, Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Tamara T. Bradford, Et Al
School of Medicine Faculty Publications
Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged < year) in the United States. In August 2023, CDC’s Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged < 8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥ 7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%-86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%-90%) against acute respiratory failure when received a median of 52 days (IQR = 32-89 days) and 50 days (IQR = 32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.
Rabies Virus-Vectored Lyme Disease Vaccine Provides Long-Term Protection Against Tick-Transmitted Borrelia Burgdorferi, Shantel Rios, Bibek Bhattachan, Christoph Wirblich, Anisha Chandwani, Kruthi Vavilikolanu, Jacob F. Myers, Chrysoula Kitsou, Utpal Pal, Matthias J. Schnell
Rabies Virus-Vectored Lyme Disease Vaccine Provides Long-Term Protection Against Tick-Transmitted Borrelia Burgdorferi, Shantel Rios, Bibek Bhattachan, Christoph Wirblich, Anisha Chandwani, Kruthi Vavilikolanu, Jacob F. Myers, Chrysoula Kitsou, Utpal Pal, Matthias J. Schnell
Department of Microbiology and Immunology Faculty Papers
Lyme disease (LD) cases have doubled globally. LD is a tick-borne illness caused by the Borrelia burgdorferi sensu lato (Bb). If untreated, Bb can disseminate to distal organs, causing carditis, arthritis, and meningitis. Currently, no FDA-approved human LD vaccine exists on the market. This study used two approaches to incorporate OspA into the rabies virus (RABV) vaccine vector. We used the RABV-glycoprotein tail (RVG tail) and the Hendra virus (HeV) glycoprotein tail (HVG tail) to incorporate OspA, creating BNSP333-OspA-RVG and BNSP333-OspA-HVG, respectively. Both vaccines produced type-1 biased anti-OspA antibodies, but only BNSP333-OspA-HVG induced neutralizing antibodies and protected against Bb infection. …
Allosteric Control Overcomes Steric Limitations For Neutralizing Antibodies Targeting Conserved Binding Epitopes Of The Sars-Cov-2 Spike Protein: Exploring The Intersection Of Binding, Allostery, And Immune Escape With A Multimodal Computational Approach, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker
Allosteric Control Overcomes Steric Limitations For Neutralizing Antibodies Targeting Conserved Binding Epitopes Of The Sars-Cov-2 Spike Protein: Exploring The Intersection Of Binding, Allostery, And Immune Escape With A Multimodal Computational Approach, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Understanding the atomistic basis of multi-layer mechanisms employed by broadly reactive neutralizing antibodies of the SARS-CoV-2 spike protein without directly blocking receptor engagement remains an important challenge in coronavirus immunology. Class 4 antibodies represent an intriguing case: they target a deeply conserved, cryptic epitope on the receptor-binding domain yet exhibit variable neutralization potency across subgroups F1 (CR3022, EY6A, COVA1-16), F2 (DH1047), and F3 (S2X259). The molecular basis for this variability is not fully understood. Here, we employed a multi-modal computational approach integrating atomistic and coarse-grained molecular dynamics simulations, binding free energy calculations, mutational scanning, and dynamic network analysis to elucidate …
Dynamic Mutational Profiling Of Binding Interactions And Allosteric Networks In Conformational Ensembles Of The Sars-Cov-2 Spike Protein Complexes With Classes Of Antibodies Targeting Cryptic Binding Sites: Confluence Of Binding And Allostery Determines Molecular Mechanisms And Hotspots Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker
Dynamic Mutational Profiling Of Binding Interactions And Allosteric Networks In Conformational Ensembles Of The Sars-Cov-2 Spike Protein Complexes With Classes Of Antibodies Targeting Cryptic Binding Sites: Confluence Of Binding And Allostery Determines Molecular Mechanisms And Hotspots Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
The ongoing evolution of SARS-CoV-2 variants has underscored the need to understand not only the structural basis of antibody recognition but also the dynamic and allosteric mechanisms that could underlie complexity of broad and escape-resistant neutralization. In this study, we employed a multi-scale approach integrating structural analysis, hierarchical molecular simulations, mutational scanning and network-based allosteric modeling to dissect how Class 4 antibodies (represented by S2X35, 25F9, and SA55) and Class 5 antibodies (represented by S2H97, WRAIR-2063 and WRAIR-2134) can modulate conformational behavior, binding energetics, allosteric interactions and immune escape patterns of the SARS-CoV-2 spike protein. Using hierarchical simulations of the …
Multiscale Modeling And Dynamic Mutational Profiling Of Binding Energetics And Immune Escape For Class I Antibodies With Sars-Cov-2 Spike Protein: Dissecting Mechanisms Of High Resistance To Viral Escape Against Emerging Variants, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker
Multiscale Modeling And Dynamic Mutational Profiling Of Binding Energetics And Immune Escape For Class I Antibodies With Sars-Cov-2 Spike Protein: Dissecting Mechanisms Of High Resistance To Viral Escape Against Emerging Variants, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
The rapid evolution of SARS-CoV-2 has underscored the need for a detailed understanding of antibody binding mechanisms to combat immune evasion by emerging variants. In this study, we investigated the interactions between Class I neutralizing antibodies—BD55-1205, BD-604, OMI-42, P5S-1H1, and P5S-2B10—and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein using multiscale modeling, which combined molecular simulations with the ensemble-based mutational scanning of the binding interfaces and binding free energy computations. A central theme emerging from this work is that the unique binding strength and resilience to immune escape of the BD55-1205 antibody are determined by leveraging a broad epitope …
Kshv Vil6 Inhibits Functional B Cell Maturation During De Novo Infection, Wajd Zakir, Jessica M. Osborn, Jennifer Totonchy
Kshv Vil6 Inhibits Functional B Cell Maturation During De Novo Infection, Wajd Zakir, Jessica M. Osborn, Jennifer Totonchy
Pharmacy Faculty Articles and Research
Despite causative links to lymphoproliferative disorders, little is known about early events governing KSHV infection in B lymphocytes. IL-6 signaling plays a critical role in KSHV-mediated disease, with human IL-6 (hIL6) levels correlating with viral load and disease progression. This dynamic is even more complex due to the coexistence of hIL6 and KSHV-encoded viral IL-6 (vIL6) in these diseases. We hypothesize that hIL6 and vIL6 play critical, separable and collective roles in the early stages of KSHV infection in B cells. In this study, we use our ex vivo model of KSHV infection in human tonsil lymphocytes to investigate the …
Characterization Of Immunogenicity Of Hiv Mrna Vaccine In Humanized Mice, Omoyeni Precious Adejare
Characterization Of Immunogenicity Of Hiv Mrna Vaccine In Humanized Mice, Omoyeni Precious Adejare
Biotechnology Theses
Human Immunodeficiency Virus (HIV) remains a leading global cause of mortality. Despite decades of research, a definitive cure or an effective vaccine for HIV infection has yet to be discovered. The major target for HIV vaccine development is the envelope (Env) trimeric protein that is responsible for host cell attachment and fusion. This comprises gp120 and the transmembrane gp41. Gp140, a truncated form of gp160(full envelope trimer) lacks the transmembrane and cytoplasmic domains of gp41, closely mimics the native HIV envelope has been shown to enhance the induction of broadly neutralizing antibodies (BnAbs) when used as protein vaccine in previous …
Integrating Positive Psychology And Spirituality To Foster Meaning And Well-Being In Older Adults, Crystal Morris
Integrating Positive Psychology And Spirituality To Foster Meaning And Well-Being In Older Adults, Crystal Morris
Adultspan Journal
This perspective article explores the integration of positive psychology interventions (PPIs) and spirituality in therapy to foster meaning and well-being in older adults. It highlights exercises such as the positive introduction, positive legacy, character strengths, mindfulness, mindful-based yoga, and a manifestation prayer journaling. The interventions presented are tools to support older adults that may experience depression, difficult life transitions, and the search for renewed meaning. Therapists who integrate PPIs and spirituality into therapy can promote a holistic, non-pathological approach to treatment.
Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire
Expanding Inducible Epithelial Resistance Against Pneumonia: Novel Virus, Novel Receptor, Michael Longmire
Dissertations and Theses (Open Access)
Pneumonia is the leading infectious cause of death worldwide and presents a continuing risk among immunocompromised patients. Our work has been focused for many years on the phenomenon of inducible epithelial resistance, where activation of the innate immune response in the airway epithelium is necessary and sufficient to produce a pathogen-killing but self-protective environment to prevent severe disease. Inducible resistance is pathogen-agnostic and has been demonstrated against an array of respiratory infections. We achieve this using a combination of pattern recognition receptor agonists – Pam2CSK4 and ODN M362 being the current formulation – which produce synergistic levels of pathogen reduction …
Quantitative Characterization And Prediction Of The Binding Determinants And Immune Escape Hotspots For Groups Of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling Of The Sars-Cov-2 Spike Complexes With Antibodies, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker
Quantitative Characterization And Prediction Of The Binding Determinants And Immune Escape Hotspots For Groups Of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling Of The Sars-Cov-2 Spike Complexes With Antibodies, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
A growing body of experimental and computational studies suggests that the cross-neutralization antibody activity against Omicron variants may be driven by the balance and tradeoff between multiple energetic factors and interaction contributions of the evolving escape hotspots involved in antigenic drift and convergent evolution. However, the dynamic and energetic details quantifying the balance and contribution of these factors, particularly the balancing nature of specific interactions formed by antibodies with epitope residues, remain largely uncharacterized. In this study, we performed molecular dynamics simulations, an ensemble-based deep mutational scanning of SARS-CoV-2 spike residues, and binding free energy computations for two distinct groups …
Asymmetric Synthesis Of The Hiv Protease Inhibitor Tmc-126 And An Anti-Malarial Agent Via A Titanium Tetrachloride Mediated Asymmetric Glycolate Aldol Addition Reaction. Redefining The Curtius Rearrangement Reaction Via Dehomologation Of Carboxylic Acids Bearing Alpha-Leaving Groups, Kweku Amaning Affram
Theses and Dissertations
Acquired Immune Deficiency Syndrome (AIDS) and malaria are two devastating infectious diseases caused by HIV and Plasmodium parasites. AIDS is caused by HIV-1 and HIV-2, transmitted through sexual contact, blood transfusions, needle sharing, and perinatal routes. Malaria, caused by plasmodium parasites through mosquito bites. Today, millions of people around the world have been infected with HIV and malaria and much research has been done to treat it. However, despite advancements in therapeutic options, these diseases remain a significant global health threat, particularly in developing countries due to the emergence of drug-resistant strains for both HIV and malaria complicating eradication efforts. …
Induction Of Tier 2 Hiv-Neutralizing Iga Antibodies In Rhesus Macaques Vaccinated With Bg505.664 Sosip, Justin C. Smith, Prabhu S. Arunachalam, Traci H. Legere, Lisa A. Cavacini, Eric Hunter, Bali Pulendran, Rama R. Amara, Pamela A. Kozlowski
Induction Of Tier 2 Hiv-Neutralizing Iga Antibodies In Rhesus Macaques Vaccinated With Bg505.664 Sosip, Justin C. Smith, Prabhu S. Arunachalam, Traci H. Legere, Lisa A. Cavacini, Eric Hunter, Bali Pulendran, Rama R. Amara, Pamela A. Kozlowski
School of Graduate Studies Faculty Publications
BACKGROUND: A goal of mucosal human immunodeficiency virus type 1 (HIV-1) vaccines is to generate mucosal plasma cells producing polymeric IgA (pIgA)-neutralizing antibodies at sites of viral entry. However, vaccine immunogens capable of eliciting IgA neutralizing antibodies (nAbs) that recognize tier 2 viral isolates have not yet been identified. METHODS: To determine if stabilized native-like HIV-1 envelope (Env) trimers could generate IgA nAbs, we purified total IgA and IgG from the banked sera of six rhesus macaques that had been found in a previous study to develop serum nAbs after subcutaneous immunization with BG505.664 SOSIP and 3M-052 adjuvant, which is …
The Role Of Peptides In Combatting Hiv Infection: Applications And Insights, Naiera M. Helmy, Keykavous Parang
The Role Of Peptides In Combatting Hiv Infection: Applications And Insights, Naiera M. Helmy, Keykavous Parang
Pharmacy Faculty Articles and Research
Peptide-based inhibitors represent a promising approach for the treatment of HIV-1, offering a range of potential advantages, including specificity, low toxicity, and the ability to target various stages of the viral lifecycle. This review outlines the current state of research on peptide-based anti-HIV therapies, highlighting key advancements and identifying future research directions. Over the past few years, there has been significant progress in developing synthetic peptide-based drugs that target various stages of the viral life cycle, including entry and replication. These approaches aim to create effective anti-HIV therapies. Additionally, peptides have proven valuable in the development of anti-HIV vaccines. In …
Providing End-Of-Life Counseling: A Narrative Inquiry, Carol Hecht, Sibyl West
Providing End-Of-Life Counseling: A Narrative Inquiry, Carol Hecht, Sibyl West
Adultspan Journal
This qualitative study aimed to address the gap in the research related to end-of-life counseling by exploring the experiences of counselors working with clients at end of life. While counseling literature and education are lacking regarding end of life, many counselors will work alongside clients approaching death. The purpose of this study was twofold: (a) to better understand the nuanced experiences of counselors providing end-of-life counseling and (b) to explore the supports and preparations helpful for counselors to provide end-of-life counseling. A narrative approach, using the Listening Guide (Gilligan, 2015), was employed to analyze and present the stories of three …
Considerations Of Medicare Telehealth Services With Older Adults, Sonah Kho, Amanda Dediego
Considerations Of Medicare Telehealth Services With Older Adults, Sonah Kho, Amanda Dediego
Adultspan Journal
The onset of the COVID-19 pandemic set in motion a rapid expansion of mental health services offered via telehealth. With this rapid expansion came the need to examine how policy and practice should be shaped in a future where telehealth is considered common in counseling practice. For counselors to understand how to support older adult clients in using telehealth services, they must understand telehealth policy. Following the eligibility of licensed counselors to participate in Medicare, counselors need to stay abreast of regulatory changes regarding restrictions and regulations on use of telehealth for mental and behavioral health services, including video and …
Alphafold2 Modeling And Molecular Dynamics Simulations Of The Conformational Ensembles For The Sars-Cov-2 Spike Omicron Jn.1, Kp.2 And Kp.3 Variants: Mutational Profiling Of Binding Energetics Reveals Epistatic Drivers Of The Ace2 Affinity And Escape Hotspots Of Antibody Resistance, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker
Alphafold2 Modeling And Molecular Dynamics Simulations Of The Conformational Ensembles For The Sars-Cov-2 Spike Omicron Jn.1, Kp.2 And Kp.3 Variants: Mutational Profiling Of Binding Energetics Reveals Epistatic Drivers Of The Ace2 Affinity And Escape Hotspots Of Antibody Resistance, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
AlphaFold2-based atomistic predictions of structures and conformational ensembles of the SARS-CoV-2 spike complexes with the host receptor ACE2 for the most dominant Omicron variants JN.1, KP.1, KP.2 and KP.3 to examine the mechanisms underlying the role of convergent evolution hotspots in balancing ACE2 binding and antibody evasion. Using the ensemble-based mutational scanning of the spike protein residues and computations of binding affinities, we identified binding energy hotspots and characterized the molecular basis underlying epistatic couplings between convergent mutational hotspots. The results suggested the existence of epistatic interactions between convergent mutational sites at L455, F456, Q493 positions that protect and restore …
A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda
A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda
Theses & Dissertations
Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …
Csf1r Inhibition Depletes Brain Macrophages And Reduces Brain Virus Burden In Siv-Infected Macaques, Diana G. Bohannon, Laurent D. Zablocki-Thomas, Evan S. Leung, Jinbum K. Dupont, Julian B. Hattler, Jolanta Kowalewska, Miaoyun Zhao, Jiangtao Luo, Marco Salemi, Angela M. Amedee, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim
Csf1r Inhibition Depletes Brain Macrophages And Reduces Brain Virus Burden In Siv-Infected Macaques, Diana G. Bohannon, Laurent D. Zablocki-Thomas, Evan S. Leung, Jinbum K. Dupont, Julian B. Hattler, Jolanta Kowalewska, Miaoyun Zhao, Jiangtao Luo, Marco Salemi, Angela M. Amedee, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim
School of Graduate Studies Faculty Publications
Perivascular macrophages (PVMs) and, to a lesser degree, microglia are targets and reservoirs of HIV and simian immunodeficiency virus (SIV) in the brain. Previously, we demonstrated that colony-stimulating factor 1 receptor (CSF1R) in PVMs was upregulated and activated in chronically SIV-infected rhesus macaques with encephalitis, correlating with SIV infection of PVMs. Herein, we investigated the role of CSF1R in the brain during acute SIV infection using BLZ945, a brain-penetrant CSF1R kinase inhibitor. Apart from three uninfected historic controls, nine Indian rhesus macaques were infected acutely with SIVmac251 and divided into three groups (n = 3 each): an untreated control and …
Toward The Development Of A Pan-Lyssavirus Vaccine, Sabrine Ben Hamed, Jacob Myers, Anisha Chandwani, Christoph Wirblich, Drishya Kurup, Nir Paran, Matthias Schnell
Toward The Development Of A Pan-Lyssavirus Vaccine, Sabrine Ben Hamed, Jacob Myers, Anisha Chandwani, Christoph Wirblich, Drishya Kurup, Nir Paran, Matthias Schnell
Department of Microbiology and Immunology Faculty Papers
In addition to the rabies virus (RABV), 16 more lyssavirus species have been identified worldwide, causing a disease similar to RABV. Non-rabies-related human deaths have been described, but the number of cases is unknown, and the potential of such lyssaviruses causing human disease is unpredictable. The current rabies vaccine does not protect against divergent lyssaviruses such as Mokola virus (MOKV) or Lagos bat virus (LBV). Thus, a more broad pan-lyssavirus vaccine is needed. Here, we evaluate a novel lyssavirus vaccine with an attenuated RABV vector harboring a chimeric RABV glycoprotein (G) in which the antigenic site I of MOKV replaces …
Repurposing Clinically Relevant Metabolic Inhibitor Drugs, Difluoromethylornithine (Dfmo) And Orlistat, For Gammaherpesvirus Replication, Lay Paw
Honors Projects
Viruses, including herpesviruses, contribute up to 15% of all human cancers. Murine gammaherpesvirus-68 (MHV-68), a pathogen commonly found in mice, is studied due to its shared homology with several human herpesviruses. Studies done in the Delgado lab via metabolomics analysis show MHV-68 infected cells increase host cell metabolism. Clinically relevant metabolic inhibitor drugs, ɑ-Difluoromethylornithine (DFMO) and Orlistat, respectively block polyamine and lipid production demonstrated a reduction in MHV-68 viral production. Repurposing clinically relevant drugs through the exploration of a different target shows great promise in reducing oncogenic viral titer.
Emotion Regulation Strategies And Perceived Emotional Intelligence: The Effect Of Age., Iwanna Sepiadou
Emotion Regulation Strategies And Perceived Emotional Intelligence: The Effect Of Age., Iwanna Sepiadou
Adultspan Journal
The aim of this study was to investigate the relationship between perceived emotional intelligence and the reported use of cognitive reappraisal and expressive suppression. We also investigated the possible effects of age on the aforementioned variables. The total sample consisted of 379 people (158 men, 220 women, 1 unreported). Across participants, 273 were young (20-39 years old) and 106 were middle-aged (40-65 years old). We found statistically significant positive correlations between the dimensions of perceived emotional intelligence and the reported use of cognitive reappraisal and negative primarily correlations between the dimensions of perceived emotional intelligence and the reported use of …
Translational Pathways For Ultra Long-Acting Medicines For Chronic Disease: From Hiv To Substance Use Disorders, Suyash Sanjay Deodhar
Translational Pathways For Ultra Long-Acting Medicines For Chronic Disease: From Hiv To Substance Use Disorders, Suyash Sanjay Deodhar
Theses & Dissertations
Human immunodeficiency virus (HIV) and opioid use disorder (OUD) are among the top global public health challenges, with a significant overlap in the number of cases and higher mortality risks compared to the general population. Treatment and recreational opioid use lead to addictive disorders. Both conditions require repeated dosing of therapy where adherence to a strict lifelong regimen remains a major challenge. Notably, people living with HIV/AIDS (PLWHA) and struggling with opioid use disorders (OUD) show suboptimal adherence to antiretroviral drugs (ARVs). Also, the risk of transmitting HIV and other blood-borne infections through the sharing of needles and other injection …
Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das
Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das
Theses & Dissertations
Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …
Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith
Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith
Theses & Dissertations
Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …
What Is The Efficacy Of The Newly Developed Hpv Vaccine, Cecolin, In Providing Protection Against Hpv-Induced Cervical Cancers In Females Aged 9-14 Years Old, Yolanda Williams
What Is The Efficacy Of The Newly Developed Hpv Vaccine, Cecolin, In Providing Protection Against Hpv-Induced Cervical Cancers In Females Aged 9-14 Years Old, Yolanda Williams
Rowan-Virtua Research Day
In low to middle income countries, there's a rise in invasive cervical squamous cell carcinoma. Affordability emerges as a crucial factor influencing this trend. This research is based on the development of a new HPV vaccine made in China called Ceolin priced at $47 and its efficacy to be incorporated into the WHO vaccination program. A peer review was conducted based on an ongoing randomized phase 3 clinical trial of a 2 dose regimen bivalent Cecolin vaccine (types 16,18) . The study includes 1025 females aged 9-14 years old split amongst 5 groups. The control group received Gardasil at the …
Out Of Time: Altered Mental Status And Temporal Seizure On Background Of Dementia & Uti, Jennifer Nguyen, Victoria Wong Murray, Judith Anne Lightfoot, Mukarram Razvi, Kasturi Etukuru
Out Of Time: Altered Mental Status And Temporal Seizure On Background Of Dementia & Uti, Jennifer Nguyen, Victoria Wong Murray, Judith Anne Lightfoot, Mukarram Razvi, Kasturi Etukuru
Rowan-Virtua Research Day
Herpes simplex virus is common in the US, with an estimated seroprevalence of HSV-1 of 40% and HSV-2 of 11%. Although herpes encephalitis is rare, with an incidence of roughly 1/100,000 individuals per year in the US, the mortality rate of 70% and rapid progression make identification and treatment imperative.
An 85 year old woman was brought to the emergency department from nursing home with altered mental status of unknown duration in refractory status epilepticus on a background of dementia, history of multiple falls, and indwelling foley catheter in addition to hypertension and bilateral knee replacement. EEG demonstrated abnormal discharges …