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Microbial
Pathogenesis
Organisms which cause chronic disease have a unique relationship with
their environment. Whether a parasite, such as an African trypanosome,
or an opportunistic pathogen, like Candida albicans, each must evolve
strategies for their persistence, transmission and replication in either
an immunocompetent or immunocompromised host. Moreover, the pattern of
gene expression can vary significantly in the different microenvironments
provided by specific tissue and organ systems. Our laboratory is interested
in discovering and investigating the underlying mechanisms of pathogenesis
for both protozoan and fungal pathogens at the molecular and genetic level.
Most recently we have been using the genomic sequence derived for the
fungus, Candida albicans to develop DNA microarrays which will allow genome-wide
expression analysis. For the first time we are able to look at the interrelationships
between genes and biological pathways and to determine the patterns of
gene expression in different disease presentations, at lesions in different
host tissues and to compare the human disease with that replicated in
relevant animal models. This technology is being applied to the characterization
of virulence factors and mechanisms of pathogenesis for this opportunistic
pathogen.
Selected Publications:
Chapman, A., Agabian, N. (1994). Phosphorylation of the C-terminal domain
of trypanosome RNA polymerase II in transcription. J. Biol. Chem. 269:
4754-4760.
Agabian, N., Odds, F.C., Poulain, D., Soll, D. and White, T.C. (1995).
Pathogenesis of invasive candidiasis. J. Med. Vet. Mycol. 32: 229-237.
Dungan, J., Watkins, K. and Agabian, N. (1996). Evidence for the presence
of a small U5-like RNA in active trans-spliceosomes of Trypanosoma brucei.
EMBO J. 15: 4016-4029.
Kohler, G., White, T.C. and Agabian, N. (1997). Overexpression of a cloned
IMP dehydrogenase gene of Candida albicans confers resistance to the specific
inhibitor mycophenolic acid. J. Bacteriol. 179: 2331-2338.
Newport, G. and Agabian, N. (1997). KEX2 influences Candida albicans proteinase
secretion and hyphal formation. Submitted to J. Biol. Chem.
Byington, C.L., Dunbrack, R.L., Jr., Witby, F.G., Cohen, F.E. and Agabian,
N. (1997). Entamoeba histolytica: Computer-assisted modeling of phosphofructokinase
for the prediction of broad spectrum antiparasitic agents. Submitted to
Expt'l. Parasitol.
Harris, E., Kropp, G., Rodriguez, B., and Agabian, N. (1998) A single-step
PCR assay for characterization of New World Leishmania complexes. J. Clin.
Microbiol., 36(7).
Roberts, T.G., Sturm, N.R., Yee, B.K., Yu, M.C., Hartshorne, T., Agabian,
N., and Campbell, D.A. (1998) Three small nucleolar RNAs from the spliced
leader-associated RNA locus in the kinetoplastid protozoa. Mol. & Cel.
Biol., 18(8)
Hoover, C.I., Jantapour, M.J., Newport, G., Agabian, N. and Fisher, S.J.
(1998) Cloning and Regulated Expression of the Candida albicans Phospholipase
B (PLB1) Gene. FEMS Microbiology Letters 167:163-169.
Naglik, J., Sweet, S., Challacombe, S., Fernandes-Naglik, L., White, T.C.,
Newport, G., Greenspan, J., Greenspan, D. and Agabian, N. (1999) In vivo
Analysis of Secreted Aspartyl Proteinase Expression in Human Oral Candidiasis.
Infection and Immunity, 67(5):2482-2490.
Cano, M.I., Dungan, J., Agabian, N., Blackburn, E.H. Telomerase in Kinetoplastid
parasitic protozoa. Proceedings of the National Academy of Sciences. (1999)
96:3616-3621.
Tzung, Keh-Weei, Williams, R.M., Scherer, S., Federspiel, N., Jones, T.,
Hansen, N., Bivolarevic, V., Huizar, L., Komp, C., Surzycki, R., Tamse,
R., Davis, R.W., Agabian, N. (2001) Genomic Evidence for a Complete Sexual
Cycle in Candida albicans. PNAS, 98(6):3249-3253.
Contact Information:
Email: agabian@itsa.ucsf.edu
Phone: 415/ 476-6845
Address: Box 0422, Room C 740
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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