Digital Commons Network^™

Inclusion Of Patient-Centered, Non-Microbiological Endpoints And Biomarkers In Tuberculosis Drug Trials, Andrew R Dinardo, Wilbert Sabiiti, Stephen H Gillespie, Sophia B Georghiou, Norbert Heinrich, Norbert Hittel, Sami Taghlabi, Danna Carrero Longlax, Mikashmi Kohli, Ursula Panzner, Collins Musia, Christoph Lange, Anca Vasiliu, Rob J W Arts, Anna M Mandalakas, Morten Ruhwald, Lieven J Stuyver, Reinout Van Crevel

Faculty, Staff and Students Publications

Tuberculosis drug trials are primarily designed to identify antibiotic regimens with the strongest potency to kill Mycobacterium tuberculosis. However, microbiologic cure is not synonymous with improved health and recovery. Beyond antimicrobial efficacy, parameters such as morbidity and mortality related to lung function, cardiovascular health, and cancer should be prioritized. This narrative review emphasizes the critical need to emphasize clinical outcomes as much, if not more, than microbiological endpoints. We examine the underlying pathophysiological mechanisms and determinants of non-microbiological outcomes in tuberculosis, providing a synthesis of current knowledge. While there is growing evidence for some biomarkers to risk stratify TB …

Avatars And Digital Identity: Branding In The Metaverse, Gema Bonales-Daimiel, Belén Moreno-Albarracín

Faculty Research, Scholarly, and Creative Activity

Considering avatars as virtual identities in digital universes, and according to the scarcity of previous research on the impact generated by them, this study delves into avatars’ emergence as personal brands within metaverses, assessing the mediation of AI in the design process and evaluating the impact of avatars on user experience and advertising. After carrying out a mixed methodology based on a survey to users, interviews to active companies in metaverses and avatars design specialists; and a content analysis of metaverse platforms, it’s been proved that avatars are revolutionizing digital communications, allowing immersive interactions and the implementation of virtual experiences …

Finding Floral And Faunal Species Richness Optima Among Active Fire Regimes, Zachary L. Steel, Alissa M. Fogg, Raphaela Floreani Buzbee, Kate Wilkin, Brandon M. Collins, Ryan Burnett, Marc D. Meyer, Amarina Wuenschel, Scott L. Stephens

Faculty Research, Scholarly, and Creative Activity

Changing fire regimes have important implications for biodiversity and challenge traditional conservation approaches that rely on historical conditions as proxies for ecological integrity. This historical-centric approach becomes increasingly tenuous under climate change, necessitating direct tests of environmental impacts on biodiversity. At the same time, widespread departures from historical fire regimes have limited the ability to sample diverse fire histories. We examined 2 areas in California's Sierra Nevada (USA) with active fire regimes to study the responses of bird, plant, and bat communities to a broad spectrum of temporal, spatial, and severity patterns of fire. Bird and plant species richness peaked …

Biallelic Variation In The Choline And Ethanolamine Transporter Flvcr1 Underlies A Severe Developmental Disorder Spectrum, Daniel G Calame, Jovi Huixin Wong, Puravi Panda, Dat Tuan Nguyen, Nancy C P Leong, Riccardo Sangermano, Sohil G Patankar, Mohamed S Abdel-Hamid, Lama Alabdi, Sylvia Safwat, Kyle P Flannery, Zain Dardas, Jawid M Fatih, Chaya Murali, Varun Kannan, Timothy E Lotze, Isabella Herman, Farah Ammouri, Brianna Rezich, Stephanie Efthymiou, Shahryar Alavi, David Murphy, Zahra Firoozfar, Mahya Ebrahimi Nasab, Amir Bahreini, Majid Ghasemi, Nourelhoda A Haridy, Hamid Reza Goldouzi, Fatemeh Eghbal, Ehsan Ghayoor Karimiani, Amber Begtrup, Houda Elloumi, Varunvenkat M Srinivasan, Vykuntaraju K Gowda, Haowei Du, Shalini N Jhangiani, Zeynep Coban-Akdemir, Dana Marafi, Lance Rodan, Sedat Isikay, Jill A Rosenfeld, Subhadra Ramanathan, Michael Staton, Kerby C Oberg, Robin D Clark, Catharina Wenman, Sam Loughlin, Ramy Saad, Tazeen Ashraf, Alison Male, Shereen Tadros, Reza Boostani, Ghada M H Abdel-Salam, Maha Zaki, Ali Mardi, Farzad Hashemi-Gorji, Ebtesam Abdalla, M Chiara Manzini, Davut Pehlivan, Jennifer E Posey, Richard A Gibbs, Henry Houlden, Fowzan S Alkuraya, Kinga Bujakowska, Reza Maroofian, James R Lupski, Long N Nguyen

Faculty, Staff and Students Publications

Purpose: FLVCR1 encodes a solute carrier protein implicated in heme, choline, and ethanolamine transport. Although Flvcr1-/- mice exhibit skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia (DBA), biallelic FLVCR1 variants in humans have previously only been linked to childhood or adult-onset ataxia, sensory neuropathy, and retinitis pigmentosa.

Methods: We identified individuals with undiagnosed neurodevelopmental disorders and biallelic FLVCR1 variants through international data sharing and characterized the functional consequences of their FLVCR1 variants.

Results: We ascertained 30 patients from 23 unrelated families with biallelic FLVCR1 variants and characterized a novel FLVCR1-related phenotype: severe developmental disorders with profound developmental delay, microcephaly …

Toward Precision Longevity: Aging Interventions In The Single-Cell Atlas Era, Jason B Chen, Miranda C Wang, Shangyu Gong, Hongjie Li

Faculty, Staff and Students Publications

With growing global interest in extending not only lifespan but also healthspan, healthy aging has emerged as a central goal in biomedical research. This review provides an overview of current longevity interventions, including genetic manipulations, dietary restriction, exercise, pharmacological treatments, targeting senescence and cellular reprogramming strategies, as studied in key model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. We examine the limitations and challenges associated with these approaches, particularly their variability across tissues and cell types. Furthermore, we emphasize the critical role of single-cell aging atlas technologies in uncovering cell-type–specific aging patterns and molecular …

Efficacy Of Nampt Inhibition In T-Cell Acute Lymphoblastic Leukemia, Chelsea Vrana, Matthew Zhang, Max Rochette, Michelle Alozie, Hailey Oviedo, Alan Gonzalez, Jaden Sherman, Barry Zorman, Pavel Sumazin, Karen R Rabin, Jacob J Junco

Faculty, Staff and Students Publications

Novel agents targeting upregulated signaling pathways are needed to improve outcomes in T-cell acute lymphoblastic leukemia (T-ALL), since conventional cytotoxic chemotherapy regimens have reached the limits of tolerability. We identified upregulated, targetable signaling pathways common to both human T-ALL samples and a KrasLSL-G12D/+.Mb1Cre/+ murine model of T-ALL. We found the NAMPT inhibitor FK866 had the greatest cytotoxicity of a panel of small molecule inhibitors tested in human and mouse T-ALL cell lines, and in patient derived xenograft (PDX)-expanded T-ALL patient samples. We subsequently tested FK866 in vivo in PDX mouse models of T-ALL, and found that it significantly reduced the …

The Association Of Human Milk Intake And Outcomes In Biliary Atresia, Mary Elizabeth M Tessier, Jeremy M Schraw, Stacey Beer, Sanjiv Harpavat, M Kyle Jensen, John C Magee, Vicky Ng, Michael E Scheurer, Sarah A Taylor, Benjamin L Shneider

Faculty, Staff and Students Publications

Objectives: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.

Methods: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ = total bilirubin (TB) < 2 mg/dL by 3 months post-KP). Secondary outcomes included 2-year survival with native liver (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n = 8) comparing AHM versus FO.

Results: At baseline, 211 infants received AHM and 215 received …

Designing And Implementing Solution-Oriented Team Science Initiatives-A Chronic Pain Example, Nele A Haelterman, Armen N Akopian, Kyle D Allen, Yenisel Cruz-Almeida, Christopher R Donnelly, Brendan Lee, Rebecca Lenzi, Anne-Marie Malfait, Marie Mancini, Maryann E Martone, Joost B Wagenaar, Kim C Worley

Faculty, Staff and Students Publications

Large, collaborative projects that combine researchers from multiple scientific disciplines have become an integral part of the scientific endeavor. While transdisciplinary team science projects hold great potential, they also come with a unique set of challenges compared to monodisciplinary projects. The Science of Team Science (SciTS) field has developed multiple conceptual models and frameworks that guide the design, implementation, and evaluation of team science initiatives to maximize their potential for making breakthrough discoveries and creating solutions for complex problems. While these conceptual models contain a trove of valuable information for successful team science, guidance on how to effectively implement them …

Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Assessing The Cardioprotective Effects Of Exercise In Apoe Mouse Models Using Deep Learning And Photon-Counting Micro-Ct, Alex J Allphin, Rohan Nadkarni, Zay Y Han, Darin P Clark, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: The allelic variations of the apolipoprotein E (APOE) gene play a critical role in regulating lipid metabolism and significantly impact cardiovascular disease risk (CVD). This study aimed to evaluate the impact of exercise on cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT) and deep learning-based segmentation.

Methods: A total of 140 mice were grouped based on APOE genotype (APOE2, APOE3, APOE4), sex, and exercise regimen. All mice were maintained on a controlled diet to isolate the effects of exercise. Low dose cardiac photon counting micro-CT imaging with intrinsic gating was performed …

Nanoparticle Contrast-Enhanced Computed Tomography Of Sporadic Aortic Aneurysm And Dissection: Effect Of Nanoparticle Size And Contrast Agent Dose, Laxman Devkota, Chen Zhang, Deborah Vela, Poonam Sarkar, Prajwal Bhandari, Zbigniew Starosolski, Renuka Menon, Dianna M Milewicz, Ying H Shen, Scott A Lemaire, Ketan B Ghaghada

Faculty, Staff and Students Publications

Background: Aortopathies, such as aortic aneurysm and dissection (AAD), are associated with enhanced aortic wall permeability and endothelial dysfunction. We previously demonstrated that nanoparticle contrast-enhanced computed tomography (nCECT), which detects enhanced aortic wall permeability, could enable non-invasive detection of early AAD before its progresses to fatal aortic rupture. This study investigated the effect of nanoparticle contrast agent (NPCA) size and dose on detection of aortopathy by nCECT.

Methods: In vivo studies were performed in a mouse model of sporadic AAD induced by challenging animals with high fat diet (5 weeks) and angiotensin II infusion (last one week). The effects …

Towards A Map Of The Immune System Manipulation Network By Trypanosoma Cruzi, Juan Cruz Gamba, Ana Rosa Pérez, Carolina Verónica Poncini, Cristina Poveda, Iván Marcipar, Gabriel Cabrera

Faculty, Staff and Students Publications

No abstract provided.

Microbiota Dynamics During Ascaris Suum Larval Migration: Implications For Host Microbial Communities In A Murine Model, Sergio Castañeda, Cristina Poveda, Charlie Suarez-Reyes, Yifan Wu, Noah Haugen, Luz H Patiño, Jill E Weatherhead, Juan David Ramírez

Faculty, Staff and Students Publications

The complex interactions between parasites, their hosts, and associated microbiota hold significant implications for host health and disease outcomes. Helminths like Ascaris lumbricoides and Ascaris suum can significantly alter the host's intestinal microbiota, affecting both parasite biology and host pathology. Despite extensive research on host-microbiota changes due to helminth infections, the study of helminth-associated microbiota remains limited. This study aims to characterize the microbiota associated with Ascaris larvae and surrounding host tissues at distinct developmental stages (day 4, day 8, day 14), during larval migration through the liver, lungs, and intestine, and its impact on the host's microbiota in a …

Histone Deacetylase 6 Inhibition Promotes Microtubule Acetylation And Facilitates Autophagosome-Lysosome Fusion In Dystrophin-Deficient Mdx Mice, Akanksha Agrawal, Erin L Clayton, Courtney L Cavazos, Benjamin A Clayton, George G Rodney

Faculty, Staff and Students Publications

Aim: Duchenne muscular dystrophy is a progressive muscle-wasting disease caused by mutations in the dystrophin gene. Despite progress in dystrophin-targeted gene therapies, it is still a fatal disease requiring novel therapeutics that can be used synergistically or alternatively to emerging gene therapy. Defective autophagy and disorganized microtubule networks contribute to dystrophic pathogenesis, yet the mechanisms by which microtubule alterations regulate autophagy remain elusive. The present study was designed to uncover possible mechanisms underpinning the role of microtubules in regulating autophagy in dystrophic mice.

Methods: Mdx mice were also supplemented with Tubastatin A, a pharmacological inhibitor of histone deacetylase 6, and …

Recognition And Management Of Persistent Chylomicronemia: A Joint Expert Clinical Consensus By The National Lipid Association And The American Society For Preventive Cardiology, Seyedmohammad Saadatagah, Miriam Larouche, Mohammadreza Naderian, Vijay Nambi, Diane Brisson, Iftikhar J Kullo, P Barton Duell, Erin D Michos, Michael D Shapiro, Gerald F Watts, Daniel Gaudet, Christie M Ballantyne

Faculty, Staff and Students Publications

Extreme hypertriglyceridemia, defined as triglyceride (TG) levels ≥1000 mg/dL, is almost always indicative of chylomicronemia. The current diagnostic approach categorizes individuals with chylomicronemia into familial chylomicronemia syndrome (FCS; prevalence 1-10 per million), caused by the biallelic combination of pathogenic variants that impair the lipolytic action of lipoprotein lipase (LPL), or multifactorial chylomicronemia syndrome (MCS, 1 in 500). A pragmatic framework should emphasize the severity of the phenotype and the risk of complications. Therefore, we endorse the term "persistent chylomicronemia (PC)" defined as TG ≥1000 mg/dL in more than half of the measurements to encompass patients with the highest risk for …

Hidden Markov Model For Acoustic Pesticide Exposure Detection And Hive Identification In Stingless Bees, Alex Otesbelgue, Amara Jean Orth, Chandler David Fong, Carol Anne Fassbinder-Orth, Betina Blochtein, Maria João Ramos Pereira

Faculty, Staff and Students Publications

Pollinator populations are declining globally at an unprecedented rate, driven by factors such as pathogens, habitat loss, climate change, and the widespread application of pesticides. Although colony losses remain difficult to prevent, precision beekeeping has introduced non-invasive strategies for monitoring hive conditions. Acoustic data, combined with machine learning techniques, has proven effective in detecting stressors and specific events in honeybee colonies; however, such methodologies remain underexplored for stingless bees, a group of native pantropical pollinators. Meliponiculture, the practice of keeping stingless bees, is an expanding field that offers significant economic and conservation benefits. Stingless bees are particularly susceptible to pesticide …

Prognostic Value Of The Monocyte-To-High-Density Lipoprotein-Cholesterol Ratio In Acute Coronary Syndrome Patients: A Systematic Review And Meta-Analysis, Michał Pruc, Jacek Kubica, Maciej Banach, Damian Świeczkowski, Zubaid Rafique, William Frank Peacock, Zbigniew Siudak, Stanisław Surma, Prabath Nanayakkara, Krzysztof Kurek, Anne Lepetit, Łukasz Szarpak

Faculty, Staff and Students Publications

Background: Globally, diseases of the cardiovascular system stand as principal contributors to mortality and are expected to show an upward trajectory. The occurrence of acute coronary syndrome (ACS) has been linked to underlying inflammatory processes. The monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) has garnered significant attention as a prognostic biomarker, encapsulating the synergistic roles of inflammation and lipid metabolism in the pathophysiology of cardiovascular diseases, including ACS.

Aims: This meta-analysis examines the prognostic MHR ratio in ACS patients.

Methods: We systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library databases to identify the relevant meta-analyses published before February 26, …

Fractalkine Inhibition Improves Survival And Reduces Tumor Immune Cell Infiltration In Orthotopic Murine Glioma Models, Eric A Goethe, Malcolm Mcdonald, Ashley Puentes, Karina Moreno, Yuhui Yang, Khatri Latha, Ganesh Rao

Faculty, Staff and Students Publications

No abstract provided.

Htr1b Is Necessary For Normal Retinal Function In Mice, Solomon E Gibson, Xiaofeng Tao, Guofu Shen, Justin Ma, Yong H Park, Maria Polo-Prieto, Benjamin J Frankfort

Faculty, Staff and Students Publications

Introduction: Serotonin (5-HT) is a neurotransmitter that is involved in retinal development, physiology, and vision, yet the specific contribution of individual 5-HT receptors to retinal function is poorly characterized. We identified 5-HT receptor 1B (Htr1b) as a potential key regulator of serotonergic signaling in the retina.

Methods: Htr1b localization was examined using RNAseq and in situ labeling. Retinal structure was assessed using histology and SD-OCT. Visual function was evaluated using optomotor behavioral experiments. Retinal function was characterized in vivo using electroretinography (ERG) and ex vivo using multielectrode array (MEA) recordings.

Results: Htr1b transcript and HTR1B protein localized primarily …

The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza

Faculty, Staff and Students Publications

The Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger transcription factor that regulates cellular processes in stem cells, epithelial cells, and immune blood cells by controlling gene expression through genetic, epigenetic, and chromatin remodeling. The landmark 2006 publication identified KLF4 as one of the factors involved in reprogramming differentiated cells into pluripotent stem cells, sparking increased interest in KLF4 research a decade after its discovery, particularly in the fields of stem cell research, epithelial cell biology, endothelial cell function, and tumorigenesis. Over the years, KLF4 has emerged as a key transcription factor in modulating innate and adaptive immunity, …

Evaluation Of Real-World Evidence To Assess Effectiveness Outcomes Of Janus Kinase Inhibitors For Rheumatoid Arthritis: A Systematic Review Of Us Studies, Chandler Gandy, Shadi Bazzazzadehgan, Sebastian Bruera, Yinan Huang

Faculty, Staff and Students Publications

Objective: This review summarized the real-world effectiveness outcomes of Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) based on observational studies.

Methods: A systematic review followed PRISMA guidelines, with searches conducted in PubMed, Embase, and CINAHL from each database's inception to June 2, 2023. Studies were included if they evaluated real-world effectiveness outcomes of JAKi for US RA patients. Search terms included "RA", "JAKi", and "real-world". All citations were imported into COVIDENCE platform. Two reviewers independently performed title/abstract screening and full-text eligibility. For each article, study characteristics and effectiveness measures focusing on treatment pattern, clinical response, and patient-reported outcomes (PROs) …

Mice With Lymphatic Dysfunction Develop Pathogenic Lung Tertiary Lymphoid Organs That Model An Autoimmune Emphysema Phenotype Of Copd, Barbara Summers, Kihwan Kim, Anjali Trivedi, Tyler M Lu, Sean Houghton, Jade Palmer-Johnson, Joselyn Rojas-Quintero, Juan Cala-Garcia, Tania Pannellini, Francesca Polverino, Raphaël Lis, Hasina Outtz Reed

Faculty, Staff and Students Publications

We have previously shown that mice with a loss of C-type lectin-like type II (CLEC2), which have lymphatic dysfunction due to the role of CLEC2 in platelets for maintaining separation between the venous and lymphatic system, develop lung tertiary lymphoid organ (TLO) formation and lung injury that resembles an emphysema phenotype of chronic obstructive pulmonary disease (COPD). We now sought to investigate whether and how TLOs in these mice may play a pathogenic role in lung injury that is relevant to human disease. We found that inhibiting TLO formation using an anti-CD20 antibody in CLEC2-deficient mice partially blocked the development …

Promotion Of Hiv Clearance By Sensitization Of Hiv Reservoirs To Cell Death, Min Li, Baichao Sun, Jing Dong, Jian-Rong Li, Laurie J Minze, Min Chen, Chao Cheng, Jin Wang

Faculty, Staff and Students Publications

Introduction: HIV integrates its proviral DNA into the host genome to establish persistent infection. To promote HIV clearance, we have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. SECH approach can clear HIV-infected cells in approximately 50% humanized mice. However, the mechanisms for the resistance of reservoirs to depletion in mice with failure in HIV clearance are unclear.

Methods: We have performed single cell transcriptome analyses of HIV-infected T cells that escaped the treatments, in order to identify cellular pathways that could be targeted to …

Inhibition Of Ribosome Biogenesis In Vivo Causes P53-Dependent Death And P53-Independent Dysfunction, Charles J Cho, Thanh Nguyen, Amala K Rougeau, Yang-Zhe Huang, Sarah To, Xiaobo Lin, Supuni Thalalla Gamage, Jordan L Meier, Jason C Mills

Faculty, Staff and Students Publications

Background & aims: Although it is well-known that ribosomes are critical for cell function, and their synthesis (known as ribosome biogenesis [RiBi]) is energy-intensive, surprisingly little is known about RiBi in vivo in adult tissue.

Methods: Using a mouse model with conditional deletion of Nat10, an essential gene for RiBi and subsequent translation of mRNA, we investigated the effects of RiBi blockade in vivo, with a focus on pancreatic acinar cells during homeostasis and tumorigenesis.

Results: We observed an unexpected latency of several weeks between Nat10 deletion and onset of structural and functional abnormalities and p53-dependent acinar cell death. Although …

Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici

Faculty, Staff and Students Publications

Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …

Dual Inhibitor Of Mdm2 And Nfat1 For Experimental Therapy Of Breast Cancer: In Vitro And In Vivo Anticancer Activities And Newly Discovered Effects On Cancer Metabolic Pathways, Wei Wang, Marlene Aguilar, Sayantap Datta, Abigail Alley, Meheret Tadesse, Xinshi Wang, Xia Gao, Ruiwen Zhang

Faculty, Staff and Students Publications

INTRODUCTION: The oncogene MDM2 has garnered attention not only for its role in cancer as a negative regulator of the tumor suppressor p53 but also for its p53-independent oncogenic activities. MDM2 also involves metabolic reprogramming, such as serine metabolism, respiration, mitochondrial functions, the folate cycle, and redox balance. Traditional MDM2 inhibitors blocking the protein-protein binding between MDM2 and p53 have shown limited clinical success in various stages of clinical trials, most likely due to low efficacy, drug toxicity, and drug resistance, highlighting the need for a novel, p53-independent strategy to inhibit MDM2. The present study investigated the antitumor effects of …

Proteomic Characterization And Comparison Of The Infective And Adult Life Stage Secretomes From Necator Americanus And Ancylostoma Ceylanicum, Yide Wong, Bruce A Rosa, Luke Becker, Mali Camberis, Graham Legros, Bin Zhan, Maria Elena Bottazzi, Ricardo T Fujiwara, Edita Ritmejeryte, Thewarach Laha, Sujittra Chaiyadet, Piyanan Taweethavonsawat, Paul J Brindley, Bethany K Bracken, Paul R Giacomin, Makedonka Mitreva, Alex Loukas

Faculty, Staff and Students Publications

More than 470 million people globally are infected with the hookworms Ancylostoma ceylanicum and Necator americanus, resulting in an annual loss of 2.1 to 4 million disability-adjusted-life-years. Current infection management approaches are limited by modest drug efficacy, the costs associated with frequent mass drug administration campaigns, and the risk of reinfection and burgeoning drug resistance. Subunit vaccines based on proteins excreted and secreted (ES) by hookworms that reduce worm numbers and associated disease burden are a promising management strategy to overcome these limitations. However, studies on the ES proteomes of hookworms have mainly described proteins from the adult life stage …

Use Of A Mouse Model For The Isolation Of Borrelia Puertoricensis From Soft Ticks, Edwin Vázquez-Guerrero, Alexander R Kneubehl, Guadalupe C Reyes-Solís, Carlos Machain-Williams, Aparna Krishnavajhala, Paulina Estrada-De Los Santos, Job E Lopez, José Antonio Ibarra

Faculty, Staff and Students Publications

The isolation of tick-borne relapsing fever (TBRF) spirochetes has proven to be a useful tool to understand their distribution in geographic areas where the tick vectors inhabit. However, their isolation and culture are not easy and in general an animal model is needed to achieve this task. Here, argasid ticks were collected from a neighborhood in Ciudad Caucel, and they were identified as Ornithodoros (Alectorobius) puertoricensis. To determine whether these were infected with TBRF bacteria they were fed with healthy mice but only a low burden of spirochetes was observed. An immunosuppressed mouse model was used to feed the ticks …

A Multifunctional Theranostic Ultrasound Platform For Remote Magnetogenetics And Expanded Blood-Brain Barrier Opening, Alec J Batts, Fotios N Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha L Gorman, Deny Tsakri, Rebecca L Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T Robinson, Elisa E Konofagou

Faculty, Staff and Students Publications

Introduction: Brain stimulation techniques are critical for unraveling the innerworkings of complex neuronal pathways governing both normal physiological function and pathologic states in neurological disorders. Focused ultrasound (FUS) is an emerging technique poised to significantly alter central nervous system (CNS) drug delivery and neuroscience research through non-invasive means. Magnetogenetics is a brain stimulation technique which may benefit from FUS technology in that alternating magnetic fields (AMF), like FUS, can pass through the skull without requiring surgery.

Methodology: Magnetogenetics involves the deposition of superparamagnetic iron-oxide nanoparticles (SPIONs) and overexpression of thermoreceptor transmembrane proteins (e.g. TRPV1 and TRPA1) in the brain. When …