Robert Munford, M.D.

Antibacterial Host Defense Section

Robert Munford, M.D.

Senior Clinician
Chief, Antibacterial Host Defense Section

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Robert S. Munford, M.D.

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.



M.D., Harvard Medical School, Boston, MA

M.A., Oxford University, Oxford, England

B.A., Vanderbilt University, Nashville, TN

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.

Selected Publications

Zou B, Goodwin M, Saleem D, Jiang W, Tang J, Chu Y, Munford RS, Lu M. A highly conserved host lipase deacylates oxidized phospholipids and ameliorates acute lung injury in mice. Elife. 2021 Nov 16;10:e70938.

Feng J, Jiang W, Cheng X, Zou B, Varley AW, Liu T, Qian G, Zeng W, Tang J, Zhao Q, Chu Y, Wei Y, Li X, Munford RS, Lu M. A host lipase prevents lipopolysaccharide-induced foam cell formation. iScience. 2021 Aug 19;24(9):103004.

Munford RS, Weiss JP, Lu M. Biochemical transformation of bacterial lipopolysaccharides by acyloxyacyl hydrolase reduces host injury and promotes recovery. J Biol Chem. 2020 Dec 18;295(51):17842-17851.

Lu M, Kho T, Munford RS.  Prolonged triglyceride storage in macrophages: pHo trumps pO2 and TLR4.  J 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, 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.

Visit PubMed for a complete publication listing.

Research Group

  • Robert Munford, M.D.
  • Keisuke Yamamoto
  • James Le
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