Jeffrey P. Henderson, MD, PhD
Associate Professor of Medicine and Molecular Microbiology
- Co-director, Biochemistry, Biophysics and Structural Biology (BBSB) Graduate Program in the Division of Biology and Biomedical Sciences
- BS: University of Wisconsin, Madison, WI (1994)
- PhD, Molecular Biophysics: Washington University School of Medicine, St. Louis, MO (2002)
- Medical Degree: Washington University School of Medicine, St. Louis, MO (2002)
- Residency: Barnes-Jewish Hospital at Washington University School of Medicine, St. Louis, MO (2004)
- Fellowship, Infectious Diseases: Washington University School of Medicine, St. Louis, MO (2006)
- Infectious Diseases
- Internal Medicine
My laboratory uses a multidisciplinary approach to better understand bacterial virulence and devise improved antibacterial therapeutic strategies. Many medically important bacterial pathogens colonize their hosts without causing disease. Understanding how these bacteria establish themselves and resist host defenses is therefore of particular interest. To do this, we combine patient-oriented studies with mass spectrometry to identify secreted products produced by pathogenic strains. Using this approach, a recent metabolomic analysis of colonizing E. coli strains found that production of small molecules involved in iron scavenging – called siderophores – is acquired or optimized among strains causing recurrent urinary tract infections. This microbial iron acquisition strategy may have evolved billions of years ago with formation of an oxygen-containing atmosphere and have since evolved further adaptations among pathogens.
These virulence-associated bacterial systems and the host factors with which they are coevolving are the subjects of numerous functional studies in the lab. We use both biochemical and microbiological techniques including quantitative mass spectrometry, chemical biology, bacterial biofilm culture, bacterial genetics and mouse models of infection to explore infection pathophysiology. Where network analysis identifies specific pathogen-associated proteins, rational drug design efforts are pursued involving in silico small molecule docking studies. Together, these studies are suggesting new therapeutic and diagnostic strategies for recurrent urinary tract infections and other bacterial infectious diseases.
Parker, K.S., Wilson, J., Marschall, J., Mucha, P.J., Henderson, J.P. “Network analysis reveals sex- and antibiotic resistance-associated antivirulence targets in clinical uropathogens”. ACS Infectious Diseases, 1 (11): 523–532, 2015.
Shields-Cutler, R.R., Crowley, J.R., Hung, C., Stapleton, A.E., Aldrich, C.C., Marschall, J., Henderson, J.P. “Human Urinary Composition Controls Siderocalin’s Antibacterial Activity”. Journal of Biological Chemistry, 290(26):15949-60, 2015.
Koh, E.I., Robinson, A.E., Bandara, N., Rogers, B.E., Henderson, J.P. “Copper import in Escherichia coli by the yersiniabactin metallophore system”. Nature Chemical Biology, 13(9):1016-1021, 2017.
Ohlemacher, S.I., Giblin, D.E., d’Avignon, A., Stapleton, A.E., Trautner, B.W., Henderson, J.P. “Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria”. Journal of Clinical Investigation, 127(11):4018-4030, 2017.