Microbial Pathogenesis Section
Stephen H. Leppla, Ph.D.
Chief, Microbial Pathogenesis Section
Major Areas of Research
- Structure-function relationships in bacterial protein toxins and the roles of toxins and other virulence factors in contributing to bacterial pathogenesis
- Bacterial gene regulation, interactions of bacteria and toxins with animal cells and tissues, the effects of toxins on host physiology, and the molecular mechanisms of toxin action
- Use of basic-research results in the design of vaccines and therapeutics
The Microbial Pathogenesis Section uses biochemical and genetic tools to study bacterial diseases and the factors contributing to pathogenesis. Research focuses on identification and analysis of bacterial virulence factors and their genetic regulation, and on their mechanisms of action. Structure-function analysis of bacterial proteins uses expression, mutagenesis, functional assessment, and structure determination by crystallography, etc. Knowledge from this work is used to repurpose bacterial protein toxins in the development of diagnostics, vaccines, and therapeutics.
Ph.D., University of Wisconsin
B.S., California Institute of Technology
Dr. Leppla earned a B.S. in biology from the California Institute of Technology and a Ph.D. in biochemistry from the University of Wisconsin. After postdoctoral study at the University of California-Berkeley and Brown University, he became a research scientist at the U.S. Army Medical Research Institute of Infectious Diseases in Frederick, Maryland. He moved to the National Institutes of Health in 1989 and to NIAID in 2003.
Bou-Nader C, Bothra A, Garboczi DN, Leppla SH, Zhang J. Structural basis of R-loop recognition by the S9.6 monoclonal antibody. Nat Commun. 2022 Mar 28;13(1):1641.
Merritt C, Chun EM, Fattah RJ, Silva LM, Ma QQ, Moayeri M, Paliga D, Neumann S, Heumann R, Leppla SH, Bugge TH. Imaging of anthrax intoxication in mice reveals shared and individual functions of surface receptors CMG-2 and TEM-8 in cellular toxin entry. J Biol Chem. 2022 Jan;298(1):101467.
Mendenhall MA, Liu S, Portley MK, O'Mard D, Fattah R, Szabo R, Bugge TH, Khillan JS, Leppla SH, Moayeri M. Anthrax lethal factor cleaves regulatory subunits of phosphoinositide-3 kinase to contribute to toxin lethality. Nat Microbiol. 2020 Dec;5(12):1464-1471.
Liu J, Zuo Z, Sastalla I, Liu C, Jang JY, Sekine Y, Li Y, Pirooznia M, Leppla SH, Finkel T, Liu S. Sequential CRISPR-Based Screens Identify LITAF and CDIP1 as the Bacillus cereus Hemolysin BL Toxin Host Receptors. Cell Host Microbe. 2020 Sep 9;28(3):402-410.e5.
McCall RM, Sievers ME, Fattah R, Ghirlando R, Pomerantsev AP, Leppla SH. Bacillus anthracis Virulence Regulator AtxA Binds Specifically to the pagA Promoter Region. J Bacteriol. 2019 Nov 5;201(23):e00569-19.
Liu S, Liu J, Ma Q, Cao L, Fattah RJ, Yu Z, Bugge TH, Finkel T, Leppla SH. Solid tumor therapy by selectively targeting stromal endothelial cells. Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):E4079-87.
(representative of 37 total)
Liu S, Leppla SH, Bugge TH, Wein AN, Peters DE, Liu J, Chen K, inventors, United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Modified anthrax toxin protective antigen. United States patent 10,835,593. 17 November 2020.
Frankel AE, Su Y, St. Croix, B, Leppla SH, inventors: United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Antibodies to tumor endothelial marker 8. United States patent 10,273,299. 30 April 2019.
Pomerantsev A, Leppla SH, inventors: United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Protease-deficient bacillus anthracis. United States patent 10,273,548. 30 April 2019.
Chen Z, Purcell RH, Emerson SU, Leppla SH, Moayeri M, inventors: United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Monoclonal antibodies that neutralize anthrax toxins. United States patent 10,053,503. 21 August 2018.
Bachran CH, Leppla SH , inventors: United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Cytolethal distending toxin subunit B conjugated or fused to Bacillus anthracis toxin lethal factor. United States patent 9,890,369. 13 February 2018
The section uses biochemical & genetic tools to study bacterial diseases & the factors contributing to pathogenesis with focus on identification & analysis of bacterial virulence factors & their genetic regulation & on their mechanisms of action. Structure-function analysis of bacterial proteins uses expression, mutagenesis, functional assessment, structure determination by crystallography, etc.