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Robert S. Munford, M.D.
Building 33, Room 2W10A3
33 North Drive
Bethesda, MD 20892
Phone: 301-443-5753
munfordrs@niaid.nih.gov

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
    • We want to uncover the genetic and epigenetic mechanisms that alter their monocyte-macrophage differentiation and function.
  • 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
    • Candidate diseases include alcoholic liver disease, steatohepatitis, post-infectious diarrheal inflammatory bowel syndrome, sepsis-induced immunosuppression, and HIV-associated immune stimulation syndrome.
  • 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

Megan Wise, B.S.
Jessica Ray, B.A.
Yingling Huang, Ph.D.
Joel Morales-Rosado, B.S.
Robert Munford, M.D.

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Selected Publications

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.

Munford RS. Sensing gram-negative bacterial lipopolysaccharides: a human disease determinant? Infect Immun. 2008 Feb;76(2):454-65.

Shao B, Lu M, Katz SC, Varley AW, Hardwick J, Rogers TE, Ojogun N, Rockey DC, Dematteo RP, Munford RS. A host lipase detoxifies bacterial lipopolysaccharides in the liver and spleen. J Biol Chem. 2007 May 4;282(18):13726-35.

Visit PubMed for a complete publication listing.

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Last Updated October 24, 2012

Last Reviewed October 24, 2012