- Wound Healing and Treatments
- Bacterial biofilms and quorum sensing
- Planarian Biology and Electrostimulation
- Diabetic Foot Ulcer Assessment and Management
- Pressure Ulcer Prevention and Management
- Antimicrobial Peptides and Activities
- Burn Injury Management and Outcomes
- Bacteriophages and microbial interactions
- Virus-based gene therapy research
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Caveolin-1 and cellular processes
- Antimicrobial agents and applications
- Microtubule and mitosis dynamics
- Periodontal Regeneration and Treatments
- CRISPR and Genetic Engineering
- Antibiotic Resistance in Bacteria
- 3D Printing in Biomedical Research
- Skin and Cellular Biology Research
- Plant and Biological Electrophysiology Studies
- Prosthetics and Rehabilitation Robotics
- Heat shock proteins research
- Antimicrobial Resistance in Staphylococcus
- Endoplasmic Reticulum Stress and Disease
- FOXO transcription factor regulation
Indiana University School of Medicine
2018-2024
McGowan Institute for Regenerative Medicine
2023-2024
Indiana University – Purdue University Indianapolis
2018-2024
University of Pittsburgh
2023-2024
Indiana University Health
2018-2023
Indiana University
2021-2023
The Ohio State University
2014-2022
Indianapolis Zoo
2021
The Ohio State University Wexner Medical Center
2017-2019
Comprehensive Clinical Research
2019
Objective: The objective of this work was to causatively link biofilm properties bacterial infection specific pathogenic mechanisms in wound healing. Background: Staphylococcus aureus is one the four most prevalent species identified chronic wounds. Causatively linking pathology challenging. Thus, isogenic mutant stains S. with varying degree formation ability studied an established preclinical porcine model infection. Methods: Isogenic strains ( ΔrexB > USA300 ΔsarA ) biofilm-forming...
Pseudomonas aeruginosa causes devastating infections in immunocompromised individuals. Once established, P. become incredibly difficult to treat due the development of antibiotic tolerant, aggregated communities known as biofilms. A hyper-biofilm forming clinical variant aeruginosa, a rugose small-colony (RSCV), is frequently isolated from chronic and correlated with poor outcome. The these mutants during infection suggests selective advantage for this phenotype, but it remains unclear how...
Objective: This study was designed to employ electroceutical principles, as an alternative pharmacological intervention, manage wound biofilm infection. Mechanism of action a United States Food and Drug Administration-cleared wireless dressing (WED) tested in established porcine chronic polymicrobial infection model involving inoculation with Pseudomonas aeruginosa PAO1 Acinetobacter baumannii 19606. Background: Bacterial biofilms represent major complication. Resistance toward pharmacologic...
Decellularized matrices of biologic tissue have performed well as wound care dressings. Extracellular matrix-based dressings are subject to rapid degradation by excessive protease activity at the environment. Stabilized, acellular, equine pericardial collagen matrix (sPCM) dressing is flexible cross-linked proteolytic enzyme resistant. sPCM was structurally characterized utilizing scanning electron and atomic force microscopy. In murine excisional wounds, effective in mounting an acute...
An extreme chronic wound tissue microenvironment causes epigenetic gene silencing. unbiased whole-genome methylome was studied in the wound-edge of patients with wounds. A total 4,689 differentially methylated regions (DMRs) were identified skin compared unwounded human skin. Hypermethylation more frequently observed (3,661 DMRs) hypomethylation (1,028 DMRs). Twenty-six hypermethylated DMRs involved epithelial-mesenchymal transition (EMT). Bisulfite sequencing validated hypermethylation a...
Chronic wounds infected by Pseudomonas aeruginosa (Pa) are characterized disease progression and increased mortality. We reveal Pf, a bacteriophage produced Pa that delays healing of chronically in human subjects animal models disease. Interestingly, impairment wound closure Pf is independent its effects on pathogenesis. Rather, impedes keratinocyte migration, which essential for healing, through direct inhibition CXCL1 signaling. In support these findings, prospective cohort study 36...
ABSTRACT Chronic skin wounds are a significant human health concern and often complicated by infection with Pseudomonas aeruginosa Staphylococcus aureus , particularly methicillin resistant S. (MRSA). Translating the knowledge gained from extensive study of virulence mechanisms pathogenesis these bacterial species to new treatment modalities has been lacking in part due paucity animal models able recapitulate disease. Our groups recently described novel porcine chronic burn wound model for...
Abstract A 100% water-soluble surfactant polymer dressing (SPD) that is bio-compatible and non-ionic has been reported to improve wound closure in preliminary clinical studies. The mechanism of action SPD healing remains unclear. Biofilm infection a significant problem hinders proper closure. objective this study was characterize the inhibition bacterial biofilm development. Static biofilms (48 h) primary pathogens Pseudomonas aeruginosa (PA01), Staphylococcus aureus (USA300) were grown on...
Pseudomonas aeruginosa biofilms represent a major threat to health care. Rugose small colony variants (RSCV) of P. aeruginosa, isolated from chronic infections, display hyperbiofilm phenotype. RSCV are highly resistant antibiotics and host defenses. This work shows that biofilm aggregates consist two distinct bacterial subpopulations uniquely organized displaying contrasting physiological characteristics. Compared with PAO1, the extracellular polymeric substance PAO1ΔwspF presented unique...
This work represents the first study employing non-invasive high-resolution harmonic ultrasound imaging to longitudinally characterize skin wound healing. Burn wounds (day 0-42), on dorsum of a domestic Yorkshire white pig were studied non-invasively using tandem digital planimetry, laser speckle and dual mode (B Doppler) imaging. Wound depth, as measured by B-mode imaging, progressively increased until day 21 decreased thereafter. Initially, blood flow at edge up 14 subsequently regressed...
Microtubule nucleation is an essential step in the formation of microtubule cytoskeleton. We recently showed that androgen and Src promote γ-tubulin accumulation at centrosome. Here, we explore mechanisms by which regulate these processes ask whether integrins play a role. perturb integrin function tyrosine-to-alanine substitution membrane-proximal NPIY motif β1 tail show this mutant substantially decreases Because stimulation promotes interaction receptor with Src, resulting PI3K/AKT...
Chaperone-enriched domains are formed in the nuclei of cells lytically infected with herpes simplex virus type 1 (HSV-1). These domains, called VICE, for induced chaperone enriched, contain Hsc70, Hsp70, Hsp40, Hsp90, polyubiquitinated proteins, and components proteasome machinery. Accumulating evidence indicates that these sites may be utilized during infection to sequester misfolded, modified, or otherwise unwanted proteins away from viral replication compartments, robust transcription,...
Objective: This work addressing complexities in wound infection, seeks to test the reliance of bacterial pathogen Pseudomonas aeruginosa (PA) on host skin lipids form biofilm with pathological consequences. Background: PA causes chronicity. Both CDC as well NIH recognizes infection a threat leading Chronic wounds lower extremities often lead surgical limb amputation. Methods: An established preclinical porcine chronic model, infected or ceramidase mutant (PA ∆Cer ), was used. Results: We...
Objective: To evaluate if patterned electroceutical dressing (PED) is safe for human chronic wounds treatment as reported by wound care providers. Approach: This work reports a pilot feasibility study with the primary objective to determine physically observable effects of PED application on host tissue response from safety evaluation point view. For this study, patients receiving lower extremity amputation at least one open part be amputated were enrolled. Patients identified through Ohio...
In the host-microbe microenvironment, bioelectrical factors influence microbes and hosts as well interactions. This article discusses relevant mechanistic underpinnings of this novel paradigm. It also addresses how such knowledge may be leveraged to develop electroceutical solutions manage biofilm infection.
Objective: Despite advances in the use of topical and parenteral antimicrobial therapy practice early tangential burn wound excision to manage bacterial load, 60% mortality from burns is attributed biofilm infection. A low electric field (∼1 V) generated by novel FDA-cleared wireless electroceutical dressing (WED) was previously shown significantly prevent disrupt infection preclinical studies. Based on this observation, purpose clinical trial evaluate efficacy WED powered a silver-zinc...
Cytokinesis is the final stage in cell division. Although integrins can regulate cytokinesis, mechanisms involved are not fully understood. In this study, we demonstrate that integrin-regulated ERK and RSK signaling promotes successful cytokinesis. Inhibiting activation of CHO cells by a mutation integrin β1 cytoplasmic tail or with pharmacological inhibitors results accumulation midbodies formation binucleated cells. Activation expression constitutively active RAF1 suppresses mutant...