About

John Alverdy, MD, is a Professor at the University of Chicago in the Department of Surgery-General Surgery. His research focuses on studying the molecular interactions of bacteria and the intestinal mucosa to understand how life-threatening infections arise after trauma, major surgery, and during critical illness. He has developed several anti-infective polymer-based compounds that attenuate the virulence of multi-drug resistant pathogens causing severe infections in surgical patients. His laboratory investigates the regulation of microbial virulence expression, particularly in pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans, exploring how environmental cues influence virulence mechanisms. His work aims to develop clinical tools to improve patient care by understanding host-pathogen interactions and microbial virulence, utilizing approaches such as computational agent-based modeling to represent complex mechanistic details. Dr. Alverdy's background includes training at Loyola University Stritch School of Medicine, a trauma and burn fellowship at the University of California, San Francisco, and residencies in surgery at Michael Reese Hospital and Medical Center. His research is supported by NIH funding, and he has contributed to advancing knowledge in surgical infections, microbiome interactions, and therapeutic modulation of microbial virulence.

Research topics

• Biology
• Computer Science
• Medicine
• Microbiology
• Immunology
• General surgery
• Food science
• Biochemistry
• Surgery
• Gastroenterology
• Internal medicine

Selected publications

• Intestinal microbiota and butyrate depletion drive gut-derived infections in necrotizing pancreatitis

  HPB · 2020

  Senior authorCorresponding
  • Microbiology
  • Medicine
  • Biology
  DOI

• Peptide YY: a novel Paneth cell antimicrobial peptide that maintains fungal commensalism

  bioRxiv (Cold Spring Harbor Laboratory) · 2020 · 2 citations

  • Microbiology
  • Biology
  • Biochemistry

  SUMMARY Perturbed interactions between the intestinal microbes and host correlate with emergence of fungal virulence. Here we report a previously unknown role for peptide YY (PYY), a described endocrine molecule, as an antimicrobial peptide (AMP) expressed by gut immune epithelial Paneth Cells (PC). PC-PYY differs from other AMPs, including lysozyme, because of limited antibacterial activity, packaging in discrete secretory granules, and selective antifungal activity to virulent hyphae, but not yeast forms of Candida albicans . The latter action is through binding of cationic PC-PYY to the anionic hyphal surface, resulting in membrane disruption and killing. PC-PYY is compartmentalized to surface mucus, which optimizes activity and prevents conversion to endocrine PYY by dipeptidyl peptidase-IV (DPP-IV). We conclude PC-PYY is a unique AMP with selective antifungal activity that maintains gut fungal commensalism. Compromised PC-PYY action from PC dysfunction and/or mucus depletion in ileal Crohn’s disease may initiate or contribute to disease via fungal pathogenesis. Highlights ⍰ Paneth Cell PYY (PC-PYY) is an antimicrobial peptide that differs from endocrine-PYY ⍰ PC-PYY is a selective anti-fungal peptide, targeting the virulent form of C. albicans ⍰ PC-PYY is separately packaged, retained by mucus, and released by C. albicans hyphae ⍰ PC-PYY is proposed as essential for maintenance of fungal commensalism in the gut Graphical Abstract Model for Paneth cell (PC) PYY action and regulation of fungal commensalisms and potential role in the pathogenesis of ileal Crohn’s Disease (iCD) (A) In a healthy ileum, commensal yeast reside and do not stimulate PYY 1-36 release from PCs. (B) Increased virulent hyphae (purple hyphae) results in PYY 1-36 release from crypt PCs into the mucus. Hyphae are targeted by PYY 1-36 and killed (red hyphae) to manage the increased fungi community in gut. (C) In a diseased ileum such as iCD, hyphal load induces immune activation and increased inflammation through PC dysfunction (gray PCs) and decreased PYY 1-36 release or mucus depletion and PC dysfunction.

  DOI

• Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity

  Nature Communications · 2020 · 136 citations

  • Immunology
  • Microbiology
  • Biology

  Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.

  PublisherOA PDFDOI

• Difficult Decisions in Bariatric Surgery

  Difficult decisions in surgery: an evidence-based approach · 2020 · 2 citations

  1st authorCorresponding
  • Computer Science
  • Medicine
  • Surgery
  DOI

Frequent coauthors

• Eric Aoys

  Aurora St. Luke's Medical Center

  7 shared

• Valeriy Poroyko

  5 shared

• Femke van den Berg

  Bohn Stafleu van Loghum (Netherlands)

  4 shared

• Olga Zaborina

  4 shared

• Marc G. Besselink

  Cancer Center Amsterdam

  4 shared

• Marja A. Boermeester

  4 shared

• G S Moss

  4 shared

• David Burke

  University of Sydney

  4 shared

Labs

• Alverdy LabPI

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