Stephen H. Leppla, Ph.D.

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

Program Description

The Microbial Pathogenesis Section studies bacterial diseases related to biodefense pathogens. Research focuses on identification and analysis of bacterial virulence factors and their genetic regulation; structure-function analysis of bacterial proteins and other factors; disease pathogenesis; and development of diagnostics, vaccines, and therapeutics.

Biography

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.

Research Group

Group Photo: Microbial Pathogenesis Section

Member of the Microbial Pathogenesis Section, November 2016

Credit
NIAID

Front row: Megan Mendenhall, Qian Ma, Rita McCall, Andrei Pomerantsev, Kuang-Hua Chen
Back row: Jan Simper, Elyse Fischer, Jonathan Renn, Steve Leppla, Danielle O'Mard, Rasem Fattah
Not pictured: Mahtab Moayeri

Selected Publications

Chen KH, Liu S, Leysath CE, Miller-Randolph S, Zhang Y, Fattah R, Bugge TH, Leppla SH. Anthrax toxin protective antigen variants that selectively utilize either the CMG2 or TEM8 receptors for cellular uptake and tumor targeting. J Biol Chem. 2016 Oct 14;291(42):22021-22029.

Vrentas CE, Moayeri M, Keefer AB, Greaney AJ, Tremblay J, O’Mard D, Leppla SH, Shoemaker CB. A diverse set of single-domain antibodies (VHHs) against the anthrax toxin lethal and edema factors provides a basis for construction of a bispecific agent that protects against anthrax infection. J Biol Chem. 2016 Oct 7;291(41):21596-21606.

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 USA. 2016 Jul 12;113(28):E4079-87.

Pomerantsev AP, Rappole C, Chang Z, Chahoud M, Leppla SH. The IntXO-PSL recombination system is a key component of the second maintenance system for bacillus anthracis plasmid pXO1. J Bacteriol. 2016 Jun 27;198(14):1939-51.

Liu S, Zhang Y, Moayeri M, Liu J, Crown D, Fattah RJ, Wein AN, Yu ZX, Finkel T, Leppla SH. Key tissue targets responsible for anthrax-toxin-induced lethality.(link is external) Nature. 2013 Sep 5;501(7465):63-8.

Visit PubMed for a complete publication listing.

Patents

Leppla SH, Lio S, Netzel-Arnett S, Birkedal-Hansen H, Bugge T, inventors; United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Mutated anthrax toxin protective antigen proteins that specifically target cells containing high amounts of cell-surface metalloproteinases or plasminogen activator receptors. United States patent 9,403,872. 2 Aug 2016.

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 9,309,322. 12 Apr 2016.

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 8,961,975. 24 Feb 2015.

Kubler-Kielb J, Vinogradov, E, Schneerson R, Hu H, Leppla SH, Robbins JB, inventors; United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Use of saccharides cross-reactive with Bacillus anthracis spore glycoprotein as a vaccine against anthrax. United States patent 8,926,986. 6 Jan 2015.

Leppla SH, Liu S, Netzel-Arnett S, Birkedal-Hansen H, Bugge T, inventors; United States of America as represented by the Secretary of the Department of Health and Human Services, assignee. Mutated anthrax toxin protective antigen proteins that specifically target cells containing high amounts of cell-surface metalloproteinases or plasminogen activator receptors. United States patent 8,791,074. 29 Jul 2014.

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