Robert Munford, M.D.

Robert S. Munford, M.D.

Senior Clinician
Chief, Antibacterial Host Defense Section

Major Areas of Research

  • To understand the basis for the prolonged immunosuppression that develops when animals that cannot inactivate lipopolysaccharides (LPS) are exposed to LPS or to Gram-negative bacteria that make 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 define AOAH’s role in metabolizing oxidized phospholipids and endocannabinoids in vivo.

 

Program Description

Animals defend themselves from many Gram-negative bacteria by 1) sensing the lipopolysaccharide (endotoxin) 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, the mice are much more likely to die when they are challenged with virulent Gram-negative bacteria.

We recently found that the lipase that inactivates LPS, acyloxyacyl hydrolase (AOAH), also can inactivate oxidized phospholipids and an endocannabinoid, 2-arachidonoylglycerol.  Our current studies focus on establishing whether or not these activities play significant roles in vivo.  

Biography

Dr. Munford received his B.A. in history from Vanderbilt University and the 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 Service 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 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

Robert Munford, M.D.
Keisuke Yamamoto
James Le

Selected Publications

Munford RS.  Endotoxemia—menace, marker, or mistake?  J Leukocyte Biol.  2016 June; 100(4):687-698.

Lu M, Kho T, Munford RS.  Prolonged triglyceride storage in macrophages: pHo trumps pO2 and TLR4J Immunol. 2014  Aug 1;193 (3): 1392-1397.

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 vivoJ Immunol. 2011 Sep 15;187(6):3314-20.

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.

Visit PubMed for a complete publication listing.

Content last reviewed on