A5070832212- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Viral Infections and Outbreaks Research
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- SARS-CoV-2 and COVID-19 Research
- Antibiotics Pharmacokinetics and Efficacy
- HIV Research and Treatment
- Evolution and Genetic Dynamics
- Immune cells in cancer
- COVID-19 epidemiological studies
- Molecular Biology Techniques and Applications
- Hepatitis B Virus Studies
- Immune responses and vaccinations
- Cancer therapeutics and mechanisms
- Teaching and Learning Programming
- Computational Drug Discovery Methods
- Biomedical and Engineering Education
- vaccines and immunoinformatics approaches
- Bacterial Genetics and Biotechnology
- Pneumonia and Respiratory Infections
- RNA Research and Splicing
Purdue University West Lafayette
2018-2025
Regenstrief Institute
2023-2025
Bridge University
2024
Cornell University
2024
American Society For Engineering Education
2024
Carnegie Mellon University
2024
Makerere University
2024
Software (Spain)
2024
University of Cape Town
2024
University of Nigeria
2024
Granulomas are complex lung lesions that the hallmark of tuberculosis (TB). Understanding antibiotic dynamics within granulomas will be vital to improving and shortening long course TB treatment. Three fluoroquinolones (FQs) commonly prescribed as part multi-drug resistant therapy: moxifloxacin (MXF), levofloxacin (LVX) or gatifloxacin (GFX). To date, insufficient data available support selection one FQ over another, show these drugs clinically equivalent. predict efficacy MXF, LVX GFX at a...
Abstract The 2019 novel coronavirus, SARS-CoV-2, is a pathogen of critical significance to international public health. Knowledge the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale transport, and emergent tissue-scale propagation limited. Moreover, little known about immune system-virus-tissue interactions how these can result in low-level (asymptomatic) infections some cases acute respiratory distress syndrome (ARDS) others,...
Fluoroquinolones represent the pillar of multidrug-resistant tuberculosis (MDR-TB) treatment, with moxifloxacin, levofloxacin, or gatifloxacin being prescribed to MDR-TB patients. Recently, several clinical trials “universal” drug regimens, aiming treat drug-susceptible and drug-resistant TB, have included a fluoroquinolone.
Granulomas are a hallmark of tuberculosis. Inside granulomas, the pathogen Mycobacterium tuberculosis may enter metabolically inactive state that is less susceptible to antibiotics. Understanding M. metabolism within granulomas could contribute reducing lengthy treatment required for and provide additional targets new drugs. Two key adaptations nonreplicating phenotype accumulation lipid inclusions in response hypoxic conditions. To explore how these influence granuloma-scale outcomes vivo,...
Mycobacterium tuberculosis is the pathogenic bacterium that causes (TB), one of most lethal infectious diseases in world. The only vaccine against TB minimally protective, and multi-drug resistant necessitates new therapeutics to treat infection. Developing therapies requires a better understanding complex host immune response infection, including dissecting processes leading formation granulomas, dense cellular lesions associated with TB. In this work, we pair experimental computational...
Article12 September 2022Open Access Source DataTransparent process Phosphatidylserine clustering by the Ebola virus matrix protein is a critical step in viral budding Monica L Husby Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, IN, USA Institute Inflammation, Immunology and Infectious Disease (PI4D), Contribution: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Writing - original draft, review editing...
Improvement in tuberculosis treatment regimens requires selection of antibiotics and dosing schedules from a large design space possibilities. Incomplete knowledge antibiotic host immune dynamics granulomas impacts clinical trial success, variations among trials hamper side-by-side comparison regimens. Our objective is to systematically evaluate the efficacy isoniazid rifampin regimens, identify modifications these that improve outcomes. We pair spatio-temporal computational model immunity...
The standard treatment of tuberculosis (TB) takes six to nine months complete and this lengthy therapy contributes the emergence drug-resistant TB. TB is caused by Mycobacterium (Mtb) ability bacterium switch a dormant phenotype has been suggested be responsible for slow clearance during treatment. A recent study showed that replication rate non-virulent mycobacterium, smegmatis, did not correlate with antibiotic susceptibility. However, question whether observation also holds true Mtb...
Cytosolic Ca2+ signatures with specific spatiotemporal patterns play crucial roles in plant responses to biotic and abiotic stresses. Perception of microbe- or damage-associated molecular (MAMPs DAMPs) initiates signaling cascades that represent the first layer defense against pathogens known as pattern-triggered immunity (PTI). During PTI, MAMP/DAMP-induced cytosolic fluxes serve essential messengers initiation transmission signals at cellular, whole organ, systemic levels. However, these...
ABSTRACT Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ), remains a significant health challenge. Clinical manifestations of TB exist across spectrum with majority infected individuals remaining asymptomatic, commonly referred to as latent infection (LTBI). In vitro models have demonstrated that cells from LTBI can better control growth and form granuloma-like structures more quickly, compared uninfected -naïve) individuals. These in results agree animal clinical evidence...
Approximately one third of the world's population is infected with Mycobacterium tuberculosis. Limited information about how immune system fights M. tuberculosis and what constitutes protection from bacteria impact our ability to develop effective therapies for We present an in vivo systems biology approach that integrates data multiple model over length time scales into a comprehensive multi-scale multi-compartment view response describe computational models can be used study (a)...
Drug resistant tuberculosis is increasing world-wide. Resistance against isoniazid (INH), rifampicin (RIF), or both (multi-drug TB, MDR-TB) of particular concern, since INH and RIF form part the standard regimen for TB disease. While it known that suboptimal treatment can lead to resistance, remains unclear how host immune responses antibiotic dynamics within granulomas (sites infection) affect emergence selection drug-resistant bacteria. We take a systems pharmacology approach explore...
Conventional oral therapies for the treatment of tuberculosis are limited by poor antibiotic distribution in granulomas, which contributes to lengthy regimens and inadequate bacterial sterilization. Inhaled formulations a promising strategy increase efficacy reduce dose frequency. We develop multiscale computational approach that accounts simultaneous dynamics lung granuloma, carrier release kinetics, pharmacokinetics, pharmacodynamics. Using this platform, we predict rationally designed...
In vitro models of Mycobacterium tuberculosis (Mtb) infection are a valuable tool for examining host-pathogen interactions and screening drugs. With the development more complex in models, there is need tools to help analyze integrate data from these models. To this end, we introduce an agent-based model (ABM) representation between immune cells bacteria setting. This silico was used simulate both traditional spheroid cell culture by changing movement rules initial spatial layout accordance...
Tuberculosis (TB) remains a global public health threat. Understanding the dynamics of host-pathogen interactions within TB granulomas will assist in identifying what leads to successful elimination infection. In vitro models provide controllable environment study these granuloma dynamics. Previously we developed biomimetic 3D spheroid model that controls bacteria better than traditional monolayer culture counterpart. We used agent-based simulations predict mechanistic reason for this...