This candidate's commitment to basic research in the medical sciences began when she entered the Medical Scientist Training Program in 1974. She has adhered to that commitment as a tenure track faculty member of the GI research unit at Washington University. The GI division is organized such that its research faculty members have reduced clinical duties thus allowing them to pursue basic research. Her research program on protein-membrane interactions in the intestinal mucosa examines both intracellular interactions, using intestinal vitamin A binding proteins as a model system, and luminal interactions, Using E. histolytica surface proteins as a model system. In vitro models of intracellular retinoid flux within the enterocyte will be developed, using fluorescence and nuclear magnetic resonance spectroscopy to measure retinoid flux between recombinant vitamin A binding proteins and liposomes or intestinal microsomes. For this work She has taken advantage of her joint appointment in the Dept. of Biochemistry and Molecular Biophysics and has worked closely with members of the Dept. of Chemistry. Her laboratory has recently cloned and expressed a E. histolytica surface antigen, which appears to play a role in amoebic adhesion. The interactions of this protein with receptors on the intestine will be studied using target cells of colonic origin. In carrying out this work she has developed close ties with members of the Infectious Diseases Division and the Dept. of Molecular Microbiology. The RCDA would come at a critical point in her development, in that it would provide her with opportunities to learn and apply new techniques, such as nuclear magnetic resonance spectroscopy, to problems in enteric biology. It would help relieve her of additional clinical responsibilities and allow her to focus on establishing an independent research program.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Modified Research Career Development Award (K04)
Project #
5K04DK002072-02
Application #
3072632
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1992-01-01
Project End
1996-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Yong, T S; Li, E; Clark, D et al. (1996) Complementation of an Escherichia coli adhE mutant by the Entamoeba histolytica EhADH2 gene provides a method for the identification of new antiamebic drugs. Proc Natl Acad Sci U S A 93:6464-9
Li, E; Yang, W G; Zhang, T et al. (1995) Interaction of laminin with Entamoeba histolytica cysteine proteinases and its effect on amebic pathogenesis. Infect Immun 63:4150-3
Stanley Jr, S L; Zhang, T; Rubin, D et al. (1995) Role of the Entamoeba histolytica cysteine proteinase in amebic liver abscess formation in severe combined immunodeficient mice. Infect Immun 63:1587-90
Zhang, T; Li, E; Stanley Jr, S L (1995) Oral immunization with the dodecapeptide repeat of the serine-rich Entamoeba histolytica protein (SREHP) fused to the cholera toxin B subunit induces a mucosal and systemic anti-SREHP antibody response. Infect Immun 63:1349-55
Stanley Jr, S L; Tian, K; Koester, J P et al. (1995) The serine-rich Entamoeba histolytica protein is a phosphorylated membrane protein containing O-linked terminal N-acetylglucosamine residues. J Biol Chem 270:4121-6
Rong, D; Lovey, A J; Rosenberger, M et al. (1994) NMR studies of fluororetinol analogs complexed to two homologous rat cellular retinol-binding proteins. Biochim Biophys Acta 1208:136-44
Cheng, L; Norris, A W; Tate, B F et al. (1994) Characterization of the ligand binding domain of human retinoid X receptor alpha expressed in Escherichia coli. J Biol Chem 269:18662-7
Yang, W; Li, E; Kairong, T et al. (1994) Entamoeba histolytica has an alcohol dehydrogenase homologous to the multifunctional adhE gene product of Escherichia coli. Mol Biochem Parasitol 64:253-60
Norris, A W; Cheng, L; Giguere, V et al. (1994) Measurement of subnanomolar retinoic acid binding affinities for cellular retinoic acid binding proteins by fluorometric titration. Biochim Biophys Acta 1209:10-8
Zhang, Y; Li, E; Stanley Jr, S L (1993) Entamoeba histolytica: the EHZc3 cDNA clone encodes a zinc-binding protein. Exp Parasitol 77:118-20

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