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Home » ... » - Faculty » Faculty Pages » Keller, Nancy |
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Keller, Nancy
 Nancy P. Keller, PhD
Professor
Research Area: : Invasive aspergillosis in immunocompromised patients; molecular genetics of mycotoxin biosynthesis; fungal development; host-fungal interactions leading to toxin production and sporulation.
Home Dept: Plant Pathology, College of Agricultural and Life Sciences
Affiliated Depts: Molecular and Environmental Toxicology; Medical Microbiology and Immunology
Address
3476 Microbial Sciences
1550 Linden Drive
Madison, WI 53706
Phone: 608/262-9795 - Email
Research
My research focus lies in genetically dissecting those aspects of Aspergillus spp. that render them potent pathogens and superb natural product machines. Laboratory efforts focus on the elucidation 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 model Aspergillus 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%. Current efforts in the lab focus on - Epigenetic control of secondary metabolite gene clusters. We have identified a protein, LaeA, that globally regulates mycotoxin production in Aspergilli. We are currently exploring the hypothesis that LaeA regulates secondary metabolism gene clusters through a mechanism that activates facultative heterochromatin.
- Role of LaeA in Aspergillus virulence. Loss of laeA yields a hypovirulent pathogen, both in the human and plant Aspergillus spp. We are examining what parameters controlled by LaeA results in a virulent pathogen.
- Gene silencing processes: RNA interference. Current work includes assessing RNA interference strategies to control toxin production in planta and development of RNAi delivery systems to treat invasive aspergillosis.
- Host/fungal signaling. Oxylipins – oxygenated fatty acids such as prostaglandins – are ubiquitious signaling molecules produced by prokaryotes and eukaryotes alike. Our central thesis is that fungi and their hosts recognize and respond to each others oxylipin signals. Currently we are assessing the virulence of oxylipin mutants in pathogenesis and elucidating the fungal receptors recognizing oxylipins.
Publications- Garscha U, Jerneren F, Chung D, Keller NP, Hamberg M, Oliw EH. Identification of dioxygenases required for aspergillus development: Studies of products, stereochemistry and the reaction mechanism. J Biol Chem. 2007 Sep 28.
- Rohlfs M, Albert M, Keller NP, Kempken F. Secondary chemicals protect mould from fungivory. Biol Lett. 2007 22;3(5):523-5.
- Maggio-Hall LA, Lyne P, Wolff JA, Keller NP. A single acyl-CoA dehydrogenase is required for catabolism of isoleucine, valine and short-chain fatty acids in Aspergillus nidulans. Fungal Genet Biol. 2007 Jun 21.
- Shwab EK, Bok JW, Tribus M, Galehr J, Graessle S, Keller NP. Histone deacetylase activity regulates chemical diversity in Aspergillus. Eukaryot Cell. 2007 6(9):1656-64.
- Tsitsigiannis DI, Keller NP. Oxylipins as developmental and host-fungal communication signals. Trends Microbiol. 2007 15(3):109-18. Review.
- Hoffmeister D, Keller NP. Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat Prod Rep. 2007 24(2):393-416.
Check PubMed for other publications by Nancy P. Keller.
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