Ph.D., Cornell University, 1990
Address: 3476 Microbial Sciences Building
Department: Bacteriology and Medical Microbiology and Immunology
Keller lab explores genetic regulation of virulence and natural product synthesis by fungi..
Research FieldsDisease Biology
My research focus lies in genetically dissecting those aspects of Aspergillus spp.
that render them potent pathogens and superb natural product machines.
We are interested in elucidating the mechanism of fungal sporulation and
host/pathogen interactions; processes intimately linked to secondary
metabolite (e.g. mycotoxin) production. My tactic has been to use the
genetic modelAspergillus nidulans to elucidate important biological processes in this genus and then carry this information to the plant pathogens A. flavus and A. parasiticus and the human pathogen A. fumigatus.
The former two pathogens contaminate seed crops worldwide with
aflatoxin, the most potent naturally occurring carcinogen known. The
latter pathogen is now tied with Candida as
the most serious human mycopathogen in developed countries where it can
cause invasive aspergillosis, a disease with a mortality rate ranging
from 50 to 90%.
We have three major areas of focus in our lab. Recent progress has identified a global regulator of secondary metabolite gene expression, LaeA, in Aspergillus species. Loss of laeA leads to decreased pathogenicity of A. flavus and A. fumigatus. We are currently exploring the hypothesis that LaeA regulates secondary metabolism gene clusters through a mechanism that activates facultative heterochromatin. Secondly, we are exploring the use of RNA interference to control disease development both agriculturally (A. flavus) and in medical settings (A. fumigatus). Current work includes assessing RNAi constructs to control toxin production in planta and development of RNAi delivery systems to treat invasive aspergillosis. Finally, we have uncovered an oxylipin signaling pathway important in fungal/host interactions. Oxylipins − oxygenated fatty acids − are ubiquitous signaling molecules produced by prokaryotes and eukaryotes alike. We have identified the Aspergillus oxygenases responsible for oxylipin biosynthesis, find deletion of these genes affect disease development and are now exploring the cell biology of how these molecules mediate both microbe and host interactions.
Hammond, T.M., Andrewski, M.D., Roossinck,
M. and Keller N.P. 2008. Aspergillus mycoviruses are targets and
suppressors of RNA silencing. Euk Cell. 2007 Dec 7; (Epub ahead of
Brodhagen, M., Tsitsigiannis, D., Hornung, E., Goebel, C., Feussner, I. and Keller, N.P. 2008. Reciprocal oxylipin-mediated cross talk in the Aspergillusseed pathosystem. Mol Microbiol. 67:378-391.
Shwab, E., Bok, J.W., Tribus, M., Galehr, J., Graessle, S. and Keller, N.P. 2007. Histone deacetylase activity regulates chemical diversity in Aspergillus. Euk Cell. 6:1656-64.
Perrin, R.M., Fedorova, N.D., Bok, J.W., Cramer, R.A., Wortman, J.R., Kim, H.S., Nierman, W.C. and Keller, N.P. 2007. Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA. PloS Pathogens. Apr:3(4):e50.
Bok, J.W., Noordermeer, D., Kale, S.P. and Keller, N.P. 2006. Secondary metabolic gene cluster silencing in Aspergillus nidulans. Mol Microbiol. 61:1636-1645.