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Surgical Specialties >> General Surgery >> Research Programs  
General Surgery : Research Programs  
Researchers in the Section of General Surgery are conducting research in a number of areas, much of which is funded with NIH grants:
  • Pathophysiology of surgical infections (see featured story below)
  • Molecular biology of familial polyposis syndrome and solid gastrointestinal and endocrine tumors
  • Breast cancer treatment
  • Evaluation of inflammatory bowel disease

John Alverdy, M.D.
John Alverdy, M.D.
Dr. John Alverdy, Professor of Surgery, directs a research program that studies the pathophysiology of surgical infections. This program seeks to understand the mechansism by which infection and sepsis arise among critically ill patients.

Despite newer and more powerful antibiotics, the incidence and severity of sepsis continues to rise, claiming the lives of more than 200,000 Americans annually. An aging population, the development of invasive medical and surgical procedures, and the ability to rescue and sustain the lives of the most critically ill and injured patients has created an unprecedented population of patients at risk for infection and sepsis.

The working hypothesis of the Alverdy lab is that during bouts of severe physiologic stress, disruption of the normal balance of the intestinal microflora coupled with an erosion of the protective barrier of the intestinal tract defense system, creates a situation in which the normal resident flora is replaced by highly lethal pathogens. They have shown that one of these hospital-acquired pathogens, pseudomonas aeruginosa, can induce a state of lethal systemic sepsis from within the intestinal epithelial surface, in the absence of any visible pathology in the intestine, and in a subversive manner that eludes clinical detection. In fact, intestinal pseudomonas aeruginosa, if provoked by the proper physiologic cues, can cause lethal sepsis without ever leaving the intestinal tract, by a mechanism that creates a porous lining in the intestinal tract to potent toxins of this organism. In this manner, this pathogen can kill its host, at arms length from the immune system, while itself being protected by a biofilm it creates that makes it inaccessible to immune cells. Because antibiotic resistance to Pseudomonas aeruginosa has increased 70% in the last 5 years, this situation poses a real and present danger to the public.

Alverdy Research Group
Dr. Alverdy's Research Group
In an effort to combat this problem Dr. Alverdy and his colleagues have developed a novel approach to the problem. By trying to understand why P. aeruginosa would turn against (Licheng Wu, Ph.D., left; John Alverdy, M.D., center; Olga Zaborina, Ph.D., right) its host, they discovered that intestinal bacteria can "sense" that a host is under extreme physiologic stress and it "responds" by enhancing its virulence genes, such as those that produce toxins and other harmful agents. This interesting molecular dialogue has evolved so that opportunistic pathogens can kill their hosts, when they perceive them to be a liability to their survival. From the standpoint of P. aeruginosa, living in the intestinal tract of a critically ill patient is no picnic, the environment is hostile, food is in short supply, and the bacteria are constantly bombarded with antibiotics.

Using specifically designed polymers, the Alverdy lab has discovered a polymer, PEG 15-20 that interferes with this host to bacterial signaling pathway, rendering intestinal bacteria "insensate" to host stress. As such, research animals drinking this polymer are completely protected from highly lethal strains of Pseudomonas aeruginosa without the polymer having any effect on the growth and survival of the organism. In fact, Pseudomonas grows very well within this polymer, it simply cannot be signaled by the host or other Pseudomonas bacteria to alter its behavior in any way. In addition, this polymer acts like a surrogate intestinal mucin, distancing the Pseudomonas away from the intestinal epithelium so it cannot adhere and activate local and systemic immunity. This ecologically neutral and novel approach to contain rather than eliminate potential pathogens by interdicting at their lines of communication, could substantially decrease antibiotic use, superinfections, and virulent nosocomial infections following high risk surgical and medical procedures.
Copyright © 2004 The University of Chicago Department of Surgery