Samuel L Stanley,
M.D.
Professor of Medicine and Molecular
Microbiology
Office: (314) 362-1070
FAX: (314) 362-3525
E-mail: sstanley@im.wustl.edu
Office: CSRB North, Room 920A, Box 8051
My laboratory works on the protozoan parasite Entamoeba histolytica, a leading cause of illness and death worldwide. We focus on molecular aspects of amebic pathogenesis, understanding the host immune and inflammatory response to amebic infection, and developing an oral vaccine to prevent amebiasis.
One of the major efforts in the laboratory is to develop an oral vaccine to prevent amebiasis. Using differential screening of an amebic cDNA library we were able to identify and clone the gene encoding a unique serine rich E. histolytica protein (SREHP). We have begun to analyze the fine structure of the SREHP molecule, and have shown in animal studies that it represents a candidate vaccine for amebiasis. Current efforts are addressing how to package a SREHP-based vaccine to best stimulate protective mucosal immune responses. Expression of SREHP in attenuated Salmonella typhi vectors, attenuated V. cholera, and as cholera toxin fusion proteins represent approaches presently under investigation. Our interest in better understanding the host response to infection led us to develop two new models of amebic infection using severe combined immunodeficient (SCID) mice. We are currently using a SCID mouse model of amebic liver abscess (ALA) to study the role of lymphocyte-based and innate immunity in protection against ALA, and are using a SCID-HU-INT model (where human intestine is implanted into SCID mice) to study amebic infection of the gut, and other invasive bacterial infections as well. Finally, we have also focused on two molecules that may be critical for amebic pathogenesis. The first is the amebic cystine proteinase, a molecule implicated in tissue damage, and possibly amebic adhesion to extracellular matrix proteins. Current work is focused on (1) looking at the unique interaction of this proteinase with laminin, and recombinant expression of the proteinase and site directed mutagenesis to look at the role of the enzyme's active site in laminin binding: and (2) looking at the potential therapeutic effects of specific inhibitors of the proteinase in the SCID models of disease. The second molecule is a unique multifunctional enzyme (EhADH2) that is critical in the amebic fermentation pathway. This EhADH2 molecule is not found in other eukaryotes, and we are currently using expression of the recombinant EhADH2 and specific domains of the molecule for structure/function analysis, and a newly developed screening test to look for specific inhibitors of this enzyme.
See also: Molecular microbiology web page