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Laboratory of Clinical Infectious Diseases

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Robert S. Munford, M.D.

Photo of Robert S. Munford, M.D.

Senior Clinician and Deputy Chief, Laboratory of Clinical Infectious Diseases
Chief, Antibacterial Host Defense Section, LCID

Major Areas of Research

  • To understand the basis for the prolonged immunosuppression that develops after lipopolysaccharides (LPS) exposure in animals that cannot inactivate LPS
  • To understand how human cells regulate the production of acyloxyacyl hydrolase (AOAH), the LPS-inactivating enzyme
  • To look for associations between AOAH deficiency and human diseases
  • To understand how LPS and other stimulatory microbial molecules induce macrophages to accumulate and retain triglycerides and to find out how triglyceride retention contributes to pathological outcomes such as granuloma formation, fatty liver, and atherosclerosis
 

Program Description

Animals defend themselves from many Gram-negative bacteria by 1) sensing the lipopolysaccharide found in the bacterial cell wall and then 2) mounting inflammatory reactions that kill the bacteria. Our research has produced strong evidence for a new concept: In order to recover from infection, animals must kill these bacteria and inactivate their LPS. We made mice that are unable to inactivate LPS and found that they never completely recover from exposure to LPS or to bacteria that make LPS. Their macrophages and other cells remain "reprogrammed" in ways that make them respond very slowly when they are re-exposed to LPS or other microbial molecules. As a result, they are much more likely to die when they are challenged with virulent Gram-negative bacteria.

Biography

Dr. Munford received his B.A. in history from Vanderbilt University and his M.A. in animal physiology from Oxford University before attending Harvard Medical School. After training in internal medicine at Parkland Memorial Hospital, Dallas, Texas, he served as an epidemic intelligence officer at the Centers for Disease Control and Prevention, did postdoctoral research at the Rockefeller University, and completed an infectious disease fellowship at the Massachusetts General Hospital. He worked for many years as a physician-scientist at the University of Texas Southwestern Medical School in Dallas, before moving to the National Institutes of Health in 2009. His interest in bacterial lipopolysaccharides (LPS, endotoxin) began when he investigated an outbreak of meningococcal disease in São Paulo, Brazil, in 1972. His lab's major research goal has been to understand how animals inactivate these highly stimulatory molecules.

Research Group

Brian Janelsins, Ph.D.
Robert Munford, M.D.

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Selected Publications

Huang YL, Morales-Rosado J, Ray J, Myers TG, Kho T, Lu M, Munford RS. Toll-like receptor agonists promote prolonged triglyceride storage in macrophages. J Biol Chem. 2014 Jan 31;289(5):3001-12.

Lu M, Varley AW, Munford RS. Persistently active microbial molecules prolong innate immune tolerance in vivo. PLoS Pathog. 2013 May;9(5):e1003339.

Lu M, Munford RS. The transport and inactivation kinetics of bacterial lipopolysaccharide influence its immunological potency in vivo. J Immunol. 2011 Sep 15;187(6):3314-20.

Shao B, Kitchens RL, Munford RS, Rogers TE, Rockey DC, Varley AW. Prolonged hepatomegaly in mice that cannot inactivate bacterial endotoxin. Hepatology. 2011 Sep 2;54(3):1051-62.

Munford RS, Lu M, Varley AW. Kill the bacteria… and also their messengers? In: Alt FW, editor. Advances in Immunology. Vol. 103. Burlington: Academic Press; 2009. p. 29-48.

Lu M, Varley AW, Ohta S, Hardwick J, Munford RS. Host inactivation of bacterial lipopolysaccharide prevents prolonged tolerance following gram-negative bacterial infection. Cell Host Microbe. 2008 Sep 11;4(3):293-302.

Visit PubMed for a complete publication listing.

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Last Updated June 26, 2014

Last Reviewed June 26, 2014