A5102027866- Oral microbiology and periodontitis research
- interferon and immune responses
- Virus-based gene therapy research
- Atherosclerosis and Cardiovascular Diseases
- Protease and Inhibitor Mechanisms
- Herpesvirus Infections and Treatments
- Cell Adhesion Molecules Research
- Organ Transplantation Techniques and Outcomes
- Immune Response and Inflammation
- Spinal Cord Injury Research
- Systemic Lupus Erythematosus Research
- Liver Disease and Transplantation
- Streptococcal Infections and Treatments
- Chemokine receptors and signaling
- Vasculitis and related conditions
- Infective Endocarditis Diagnosis and Management
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chemotherapy-induced cardiotoxicity and mitigation
- Transplantation: Methods and Outcomes
- Wound Healing and Treatments
- Animal Virus Infections Studies
- Oral Health Pathology and Treatment
- Atrial Fibrillation Management and Outcomes
- Cytomegalovirus and herpesvirus research
- Spinal Dysraphism and Malformations
University of Florida
2012-2022
Arizona State University
2018-2021
Creighton University
2020-2021
St. Joseph Hospital
2020
Dignity Health
2017-2020
Saint Joseph's Hospital
2017-2020
St. Joseph's Hospital
2019
Florida College
2014-2017
Viron Therapeutics (Canada)
2007-2015
Malcom Randall VA Medical Center
2015
Atherosclerotic vascular disease is a leading cause of myocardial infarction and cerebrovascular accident, independent associations with periodontal (PD) are reported. PD caused by polymicrobial infections aggressive immune responses. Genomic DNA Porphyromonas gingivalis, the best-studied bacterial pathogen associated severe PD, detected within atherosclerotic plaque. We examined causal relationships between chronic P. gingivalis oral infection, atherosclerosis in hyperlipidemic ApoEnull...
The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment limited. Emerging evidence indicates that post-SCI inflammation is severe but the role reactive astrogliosis not well given its implication in ongoing as damaging or neuroprotective. We have completed an extensive systematic study with MRI, histopathology, proteomics ELISA analyses designed to further define protracted after SCI a rat model. identified 3 distinct phases SCI: acute (first 2 days),...
Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia are periodontal pathogens associated with the etiology of adult periodontitis as polymicrobial infections. Recent studies demonstrated that oral infection P. gingivalis induces both disease atherosclerosis in hyperlipidemic proatherogenic ApoE(-/-) mice. In this study, we explored expression microRNAs (miRNAs) maxillas (periodontium) spleens isolated from mice infected T. a infection. miRNA levels, including miR-146a,...
Periodontal disease (PD) and atherosclerosis are both polymicrobial multifactorial although observational studies supported the association, causative relationship between these two diseases is not yet established. Polymicrobial infection-induced periodontal postulated to accelerate atherosclerotic plaque growth by enhancing risk factors of orally infected Apolipoprotein E deficient (ApoEnull) mice. At 16 weeks infection, samples blood, mandible, maxilla, aorta, heart, spleen, liver were...
Periodontal disease (PD) develops from a synergy of complex subgingival oral microbiome, and is linked to systemic inflammatory atherosclerotic vascular (ASVD). To investigate how polybacterial microbiome infection influences plaque progression, we infected the cavity ApoEnull mice with consortium 4 well-characterized periodontal pathogens, Porphyromonas gingivalis, Treponema denticola, Tannerealla forsythia Fusobacterium nucleatum, that have been identified in human by DNA screening. We...
Tannerella forsythia is a Gram-negative anaerobic organism that inhabits the subgingival cavity and initiates connective tissue destruction alveolar bone resorption in periodontal disease (PD). PD chronic immunoinflammatory has been linked to several systemic diseases including atherosclerosis. This study evaluated effects of oral infection with T. ATCC 43037 on induction PD, inflammatory markers atherosclerosis risk factors hyperlipidemic ApoE(null) mice. Mice were orally infected for 12 24...
Treponema denticola is a predominantly subgingival oral spirochete closely associated with periodontal disease and has been detected in atherosclerosis. This study was designed to evaluate causative links between induced by chronic T. infection atherosclerosis hyperlipidemic ApoE(-/-) mice. mice (n = 24) were orally infected ATCC 35404 euthanized after 12 24 weeks. genomic DNA plaque samples, indicating colonization of the cavity. Infection elicited significantly (P 0.0172) higher IgG...
Vascular inflammation can lead to plaque instability and acute coronary syndromes (ACS). Viruses produce potent immunomodulating proteins that regulate key inflammatory pathways. A myxoma virus-derived serpin Serp-1 reduces cell invasion growth in vascular injury models. Our objective was evaluate the safety efficacy of patients with ACS undergoing percutaneous intervention.This double-blind pilot trial included 48 intervention randomly assigned at doses 5 μg/kg (n=19) or 15 (n=17) placebo...
Streptococcus mutans, a dental caries pathogen, also causes endocarditis and is detected in atheroscelerotic plaque. We investigated the potential for an invasive strain of S. OMZ175, to accelerate plaque growth apolipoprotein E deficient (ApoE(null)) mice without with balloon angioplasty (BA) injury, model restenosis. ApoE(null) were divided into 4 groups (N = 10), 2 BA. One each BA non-BA was infected mutans (Sm). DNA, area, inflammatory cell invasion, Toll-like receptor (TLR) expression...
ABSTRACT The American Heart Association supports an association between periodontal diseases and atherosclerosis but not a causal association. This study explores the use of integrin β6 −/− mouse model to causality. We investigated ability polymicrobial consortium Porphyromonas gingivalis , Treponema denticola Tannerella forsythia Fusobacterium nucleatum colonize periodontium induce local systemic inflammatory responses. Polymicrobially infected Itgβ6 mice demonstrate greater susceptibility...
The American Heart Association supports an association between periodontal disease (PD) and atherosclerotic vascular (ASVD) but does not as of yet support a causal relationship. Recently, we have shown that major pathogens Porphyromonas gingivalis Treponema denticola are causally associated with acceleration aortic atherosclerosis in ApoEnull hyperlipidemic mice. aim this study was to determine if oral infection another significant pathogen Fusobacterium nucleatum can accelerate inflammation...
Toll-like-receptors (TLRs) play a significant role in the generation of specific innate immune response against invading pathogens. TLR2 and TLR4 signaling contributes to infection-induced inflammation periodontal disease (PD) atherosclerosis. Observational studies point towards relationship between PD atherosclerosis, but recognition multiple oral pathogens their modulation host leading atherosclerosis are not clear. We evaluated induction both TLR2-/- TLR4-/- mice polymicrobial infection...
Background Binding of chemokines to glycosaminoglycans (GAGs) is classically described as initiating inflammatory cell migration and creating tissue chemokine gradients that direct local leukocyte chemotaxis into damaged or transplanted tissues. While chemokine-receptor binding has been extensively studied during allograft transplantation, effects glycosaminoglycan (GAG) interactions with on transplant longevity are less well known. Here we examine the impact interrupting chemokine-GAG...
Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits pro-inflammatory cell at the site leading to improved outcomes. We hypothesized that implantation hydrogel loaded an immune modulating biologic drug, Serp-1, for delivery after crush-induced SCI would have effective...
PURPOSE: To evaluate two experimental blood pool agents for potential use in equilibrium phase abdominal magnetic resonance (MR) angiography. MATERIALS AND METHODS: MR imaging at 0.5 T was performed 37 rabbits before and after intravenous injection of a gadolinium-based contrast agent (SH L 643 A), superparamagnetic iron oxide U 555 C), or gadopentetate dimeglumine. T1-weighted fast spoiled gradient-echo images from the renal arteries to below iliac bifurcation were obtained. The...
Summary Serpins maintain haemostasis through regulation of serine proteinases in the thrombotic and thrombolytic pathways. Viruses encode serpins that can alter responses producing, some cases, disseminated intravascular coagulation (DIC). However, it has not been precisely defined how viral induce these profound responses. The rabbit myxoma serpin, Serp-1 inhibits urokinase- tissue-type plasminogen activators (uPA tPA), plasmin factor Xa vitro exhibits remarkable anti-inflammatory activity...
Serp-1 is a secreted myxoma viral serine protease inhibitor (serpin) with proven, highly effective, anti-inflammatory defensive activity during host cell infection, as well potent immunomodulatory in wide range of animal disease models. binds urokinase-type plasminogen activator (uPA) and the tissue-type PA, plasmin, factor Xa, requiring uPA receptor (uPAR) for activity. To define Serp-1-mediated effects on inflammatory activation, we examined association monocytes T cells, cellular...
Poxviruses express highly active inhibitors, including serine proteinase inhibitors (serpins), designed to target host immune defense pathways. Recent work has demonstrated clinical efficacy for a secreted, myxomaviral serpin, Serp-1, which targets the thrombotic and thrombolytic proteases, suggesting that other viral serpins may have therapeutic application. Serp-2 CrmA are intracellular cross-class poxviral serpins, with entirely distinct functions from Serp-1 protein. block protease...
Inflammation of the retina is a contributing factor in ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration (AMD). The M013 immunomodulatory protein from myxoma virus has been shown to interfere with proinflammatory signaling pathways involving both NLRP3 inflammasome NF-κB. We have developed characterized an adeno-associated viral (AAV) vector that delivers secretable cell-penetrating form (TatM013). expressed TatM013 was secreted blocked...
Numerous treatments have been developed to promote wound healing based on current understandings of the process. Hemorrhaging, clotting, and associated inflammation regulate early healing. We investigated treatment with a virus-derived immune modulating serine protease inhibitor (SERPIN), Serp-1, which inhibits thrombolytic proteases inflammation, in mouse excisional model. Saline or recombinant Serp-1 were applied directly wounds as single doses 1 μg 2 µg two boluses. A chitosan-collagen...
Immunopathogenesis in systemic viral infections can induce a septic state with leaky capillary syndrome, disseminated coagulopathy, and high mortality limited treatment options. Murine gammaherpesvirus-68 (MHV-68) intraperitoneal infection is gammaherpesvirus model for producing severe vasculitis, colitis lethal hemorrhagic pneumonia interferon gamma receptor-deficient (IFNγR-/-) mice. In prior work, myxomavirus-derived Serp-1 or derivative peptide S-7 (G305TTASSDTAITLIPR319) induced immune...
In previous studies we have demonstrated that Serp-1, a myxoma virus encoded serine protease inhibitor, dramatically inhibits neointimal hyperplasia in vascular injury and aortic transplant models. Here examined the effect of peritransplant Serp-1 administration on chronic renal allograft rejection.Rat transplants were performed with sequential recipient sacrifice postoperative days 2, 10 140 to examine both acute effects rats.Serp-1 reduced early posttransplant (POD 2) less tubular...