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overview John Alverdy, MD, has run a continuously funded NIH-funded laboratory that studies the molecular interactions of bacteria and the intestinal mucosa in order to understand how life-threatening infections arise after trauma and major surgery and during critical illness. He has developed several anti-infective polymer-based compounds that can attenuate the virulence of several multi-drug resistant pathogens that cause life threatening infections in surgical patients and works with the IME to synthesize, refine, and scale the compounds for pre-clinical testing. The Alverdy lab seeks to better understand the regulation of virulence expression among potential pathogens through investigating the characteristics of the microbial context, molecular machinery that senses that context, and ultimately the lethal combinations of virulence expression that leads to disease. The majority of our work has focused on the sense and response virulence mechanisms of Pseudomonas aeruginosa, a well characterized and clinically important pathogen. We have shown a remarkable potential for this organisms to respond to host environmental cues related to stress, ischemia, immune activation and nutrient depletion. With this core model of environmental regulation of virulence expression, we are pursuing applications in intestinal transplantation, anastomotic and radiation physiology, necrotizing enterocolitis and ischemia/reperfusion injury. We are also investigating similar sense and response mechanisms in other clinically important organisms, including Staphylococcus aureus and Candida albicans. Finally, we are interested in developing virulence-based therapies to prevent virulence activation through modifications in microenvironment of the stressed host such as phosphate repletion and polymer-mediated mucosal replacement therapies. The ultimate goal of understanding microbial virulence is to provide clinical tools to improve the care of patients. However the complexity of the host-pathogen interaction and the vast amounts of mechanistic information available constitutes a formidable barrier to translational research. Computational agent based modeling is a well suited to dynamically represent mechanistic detail in a modifiable context to recapitulate cellular behavior at the tissue, organ and patient levels.

One or more keywords matched the following items that are connected to Alverdy, John

Item TypeName
Concept Acinetobacter Infections
Concept Bacterial Infections
Concept Clostridium Infections
Concept Cross Infection
Concept Opportunistic Infections
Concept Surgical Wound Infection
Concept Staphylococcal Infections
Concept Gram-Positive Bacterial Infections
Concept Wound Infection
Concept Pseudomonas Infections
Concept Intraabdominal Infections
Concept Infection Control
Academic Article Whole gut washout for severe sepsis: review of technique and preliminary results.
Academic Article High-molecular-weight polyethylene glycol prevents lethal sepsis due to intestinal Pseudomonas aeruginosa.
Academic Article Chronic acid water feeding protects mice against lethal gut-derived sepsis due to Pseudomonas aeruginosa.
Academic Article Depletion of intestinal phosphate after operative injury activates the virulence of P aeruginosa causing lethal gut-derived sepsis.
Academic Article Structure-function aspects of PstS in multi-drug-resistant Pseudomonas aeruginosa.
Academic Article Surgical injury and metabolic stress enhance the virulence of the human opportunistic pathogen Pseudomonas aeruginosa.
Academic Article The molecular Koch's postulates and surgical infection: a view forward.
Academic Article Prevention of siderophore- mediated gut-derived sepsis due to P. aeruginosa can be achieved without iron provision by maintaining local phosphate abundance: role of pH.
Academic Article Pseudomonas aeruginosa potentiates the lethal effect of intestinal ischemia-reperfusion injury: the role of in vivo virulence activation.
Academic Article Host stress and virulence expression in intestinal pathogens: development of therapeutic strategies using mice and C. elegans.
Academic Article Diverting loop ileostomy and colonic lavage: an alternative to total abdominal colectomy for the treatment of severe, complicated Clostridium difficile associated disease.
Academic Article Pseudomonas aeruginosa virulence expression is directly activated by morphine and is capable of causing lethal gut-derived sepsis in mice during chronic morphine administration.
Academic Article Avoiding colectomy during surgical management of fulminant Clostridium difficile colitis.
Academic Article Diagnostic peritoneal lavage in intra-abdominal sepsis.
Academic Article The intestinal environment of surgical injury transforms Pseudomonas aeruginosa into a discrete hypervirulent morphotype capable of causing lethal peritonitis.
Academic Article Phosphate-containing polyethylene glycol polymers prevent lethal sepsis by multidrug-resistant pathogens.
Academic Article The opposing forces of the intestinal microbiome and the emerging pathobiome.
Academic Article Localization of DING proteins on PstS-containing outer-surface appendages of Pseudomonas aeruginosa.
Academic Article Pseudomonas aeruginosa wound infection involves activation of its iron acquisition system in response to fascial contact.
Academic Article Agent-based model of epithelial host-pathogen interactions in anastomotic leak.
Academic Article Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Randomized, Double-Blind, Phase 3 Ceftolozane-Tazobactam Study.
Academic Article The gut microbiota and gastrointestinal surgery.
Academic Article Modeling Acinetobacter baumannii wound infections: The critical role of iron.
Academic Article The gut microbiome and the mechanism of surgical infection.
Academic Article Can Methicillin-resistant Staphylococcus aureus Silently Travel From the Gut to the Wound and Cause Postoperative Infection? Modeling the "Trojan Horse Hypothesis".
Academic Article Smoking and Postoperative Surgical Site Infection: Where There's Smoke, There's Fire.
Academic Article The Influence of Host Stress on the Mechanism of Infection: Lost Microbiomes, Emergent Pathobiomes, and the Role of Interkingdom Signaling.
Academic Article Stochasticity among Antibiotic-Resistance Profiles of Common Burn-Related Pathogens over a Six-Year Period.
Academic Article Optimum Operating Room Environment for the Prevention of Surgical Site Infections.
Academic Article Ionic Modulation of Bacterial Virulence and Its Role in Surgical Infection.
Academic Article De Novo Synthesis of Phosphorylated Triblock Copolymers with Pathogen Virulence-Suppressing Properties That Prevent Infection-Related Mortality.
Academic Article The wound environment, microbial virulence and postoperative infection: Practical lessons for the surgeon.
Academic Article Identification of Collagenolytic Bacteria in Human Samples: Screening Methods and Clinical Implications for Resolving and Preventing Anastomotic Leaks and Wound Complications.
Academic Article Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets.
Academic Article Re-examining causes of surgical site infections following elective surgery in the era of asepsis.
Academic Article Can the Cecal Ligation and Puncture Model Be Repurposed To Better Inform Therapy in Human Sepsis?
Academic Article Surgical site infections following elective surgery - Authors' reply.

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