A5022672895- Tuberculosis Research and Epidemiology
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Mycobacterium research and diagnosis
- Complement system in diseases
- SARS-CoV-2 and COVID-19 Research
- interferon and immune responses
- COVID-19 Clinical Research Studies
- Escherichia coli research studies
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Immune Response and Inflammation
- Yersinia bacterium, plague, ectoparasites research
- Reproductive System and Pregnancy
- Immunotherapy and Immune Responses
- Antimicrobial Peptides and Activities
- Vector-borne infectious diseases
- vaccines and immunoinformatics approaches
- Diagnosis and treatment of tuberculosis
- Viral Infections and Vectors
- Inflammasome and immune disorders
- Animal Virus Infections Studies
- Glycosylation and Glycoproteins Research
- Respiratory Support and Mechanisms
The University of Texas Medical Branch at Galveston
2015-2024
Texas Medical Board
2011
Mycobacterium tuberculosis (M.tb) is the second leading infectious cause of death worldwide and primary in people living with HIV/AIDS. There are several excellent animal models employed to study (TB), but many have limitations for reproducing human pathology none amenable direct HIV/M.tb co-infection. The humanized mouse has been increasingly explore HIV infection other pathogens where limiting. Our goal was develop a small model M.tb using bone marrow, liver, thymus (BLT) mouse....
The emergence of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an urgent public health crisis. Without available targeted therapies, treatment options remain limited for COVID-19 patients. Using medicinal chemistry and rational drug design strategies, we identify 2-phenyl-1,2-benzoselenazol-3-one class compounds targeting the SARS-CoV-2 main protease (Mpro). FRET-based screening against recombinant Mpro identified six that inhibit proteolysis with...
Co-infection with HIV increases the morbidity and mortality associated tuberculosis due to multiple factors including a poorly understood microbial synergy. We developed novel small animal model of co-infection in humanized mouse investigate how infection disrupts pulmonary containment Mtb. Following dual infection, HIV-infected cells were localized sites Mtb-driven inflammation mycobacterial replication lung. Consistent disease human subjects, we observed increased burden, loss granuloma...
ABSTRACT We evaluated two commercial F1 antigen capture-based immunochromatographic dipsticks, Yersinia Pestis (F1) Smart II and Plague BioThreat Alert test strips, in detecting plague bacilli by using whole-blood samples from mice experimentally infected with pestis CO92. To assess the specificities of these an in-frame F1-deficient mutant CO92 (Δ caf ) was generated homologous recombination used as a negative control. Based on genetic, antigenic/immunologic, electron microscopic analyses,...
Bacillus Calmette-Guerin (BCG) is the only vaccine against TB and has limited protection efficacy, which wanes past adolescence. Multifunctional CD8+ T cells (IFN-γ+/TNF-α+/IL-2+) are associated with lower reactivation risk enhanced control of active Mtb infection. Since boosting BCG contraindicated, booster vaccines that augment cell immunity in lungs BCG-vaccinated individuals urgently needed. We developed a vaccination strategy based on self-assembling peptide nanofibers presenting...
Rift Valley fever is a mosquito-transmitted, zoonotic disease that infects humans and ruminants. Dendritic cell specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) acts as receptor for members of the phlebovirus genus. The virus (RVFV) glycoproteins (Gn/Gc) encode five putative N-glycan sequons (asparagine (N)–any amino acid (X)–serine (S)/threonine (T)) at positions: N438 (Gn), N794, N829, N1035, N1077 (Gc). N-glycosylation profile significance in viral...
Natural killer (NK) cells have innate antibacterial activity that could be targeted for clinical interventions infectious disease caused by naturally occurring or weaponized bacterial pathogens. To determine a potential role NK in immunity to Bacillus anthracis, we utilized primary human and murine cells, vitro assays, vivo cell depletion model of inhalational anthrax. Our results demonstrate potent against B. anthracis bacilli within infected autologous monocytes. Surprisingly, also mediate...
SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. We identified the host E3-ubiquitin ligase TRIM7 as an inhibitor apoptosis replication via ubiquitination membrane (M) protein.
Tuberculosis relapse following drug treatment of active disease is an important global public health problem due to the poorer clinical outcomes and increased risk resistance development. Concurrent infection with HIV, including in those receiving anti-retroviral therapy (ART), factor for expansion resistant Mycobacterium tuberculosis (Mtb) isolates. A greater understanding HIV-associated factors driving TB development interventions that support immune containment complement therapy. We...
Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed NiV replicates to high titers human grafts NOD-SCID/γ mice, resulting robust inflammatory response. Interestingly, these mice undergo immune system reconstitution by bone marrow, liver, and thymus (BLT) method, addition tissue engraftment, giving...
Abstract Therapeutic vaccines have promise as adjunctive treatment for tuberculosis (TB) or preventives against TB relapse. An important development challenge is the limited understanding of T helper (Th) cell roles during these stages disease. A murine model relapse was used to identify changes in Th populations and cytokine microenvironment. Active promoted expansion Th1, Th2, Th17, Th22 cells cytokines lung. Following drug therapy, pulmonary Th17 contracted, Th1 remained elevated, while...
The study of HIV infection and pathogenicity in physical reservoirs requires a biologically relevant model. human immune system (HIS) mouse is an established model infection, but defects tissue reconstitution remain challenge for examining pathology tissues. We utilized exogenous injection the recombinant FMS-like tyrosine kinase 3 ligand (rFLT-3 L) into hematopoietic stem cell (HSC) cord blood HIS to significantly expand total area lymph node (LN) number circulating T cells. results enabled...
L-arginine metabolism is strongly linked with immunity to mycobacteria, primarily through the antimicrobial activity of nitric oxide (NO). The potential modulate tuberculosis (TB) outcomes interventions that target pathways are limited by an incomplete understanding mechanisms and inadequate in vivo modeling. These gaps knowledge compounded for HIV Mtb co-infections, where activation arginase-1 due infection may promote survival replication both HIV. We utilized vitro systems determine how...
Abstract The C-type lectin receptor (CLR) family plays an important role in mediating the innate immune responses to some viruses. Macrophage galactose-type (MGL), or CLEC10, is a CLR that binds SARS-CoV-2 Spike. This binding event dispensable for virus entry but has been implicated increased inflammatory response. Downstream relevant host protection against are not well described. We investigated of MGL disease pathogenesis by utilizing MGL-1 deficient mice (KO) and wild type (WT) control...
SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. Here we show the host E3-ubiquitin ligase TRIM7 acts as an inhibitor apoptosis replication via ubiquitination membrane (M) protein. Trim7-/- mice exhibit increased pathology titers associated with epithelial dysregulated immune responses. Mechanistically, ubiquitinates M on K14, which protects cells...
Abstract Mycobacterium tuberculosis (Mtb), the causative agent of (TB), is responsible for approximately 10 million new infections and 1.5 deaths each year. Pattern recognition receptors (PRRs) expressed on surface macrophages play an important role in orchestrating immune response to pathogens. Amongst these, C-type lectin (CLRs) are PRR system that increasingly understood mediate innate immunity mycobacteria. We recently described a anti-bacterial anti-inflammatory macrophage...
Abstract Mycobacterium tuberculosis (Mtb) and Human Immunodeficiency virus (HIV) are important causes of death in infected patients worldwide, act synergistically to worsen disease those with co-infection. C-type lectin receptors (CLRs) an component innate immunity that can recognize respond pathogen-associated signals. The macrophage galactose-type (MGL, CLEC10) has been described as immunomodulatory CLR associated M2 macrophages regulation inflammation following infection. Our lab...
Abstract Over a third of the world’s population is infected with Mycobacterium tuberculosis (M.tb). HIV infection significantly increases risk for M.tb and reactivation TB most common cause death among people HIV. We have developed humanized mouse model HIV-1/M.tb co-infection as an investigative tool to study biology. Humanized mice were intravenously macrophage-tropic strain HIV-1 (JR-CSF) or mock (BSA), 3 weeks later intranasally (H37Rv). Animals became productively HIV-1, confirmed by...