Fungal infections are a serious and growing problem among people with compromised immunity, including those undergoing or recovering from chemotherapy and people with HIV/AIDS. There are very few effective anti-fungal drugs, particularly when compared to the arsenal available to treat bacterial infections.

In collaboration with Dr. Damian Krysan, Dr. Melanie Wellington and the members of their laboratories, I am using a novel high-throughput assay developed in the Krysan laboratory to discover new anti-fungal compounds. We then use a variety of biochemical, genetic, and in vivo mouse experiments to characterize the compounds uncovered by the assay: to explore their mechanism of action as well as their potential utility in treating infection, either alone or in combination with other anti-fungal compounds.

Because of its unique characteristics and thus lack of overlap with the human host, we are particularly interested in compounds that affect the fungal cell wall, and we are using genetic approaches to bias our chemical library screening toward this class of compounds. The fungal cell wall is relatively poorly understood, and we expect these compounds to be useful not only in treating fungal infections, but also in helping us understand cell wall structure and function.

• Riddle MR, Baxter BK, Avery BJ. Molecular identification of microorganisms associated with the brine shrimp Artemia franciscana. Aquat Biosyst. 2013; 9(1):7.
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• Butts A, Didone L, Koselny K, Baxter BK, Chabrier-Rosello Y, Wellington M, Krysan DJ. A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis. Eukaryot Cell. 2013 Feb; 12(2):278-87.
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• Pugin B, Blamey JM, Baxter BK, Wiegel J. Amphibacillus cookii sp. nov., a facultatively aerobic, spore-forming, moderately halophilic, alkalithermotolerant bacterium. Int J Syst Evol Microbiol. 2012 Sep; 62(Pt 9):2090-6.
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• Baxter BK, DiDone L, Ogu D, Schor S, Krysan DJ. Identification, in vitro activity and mode of action of phosphoinositide-dependent-1 kinase inhibitors as antifungal molecules. ACS Chem Biol. 2011 May 20; 6(5):502-10.
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• DiDone L, Scrimale T, Baxter BK, Krysan DJ. A high-throughput assay of yeast cell lysis for drug discovery and genetic analysis. Nat Protoc. 2010; 5(6):1107-14.
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• Griffith JD, Willcox S, Powers DW, Nelson R, Baxter BK. Discovery of abundant cellulose microfibers encased in 250 Ma Permian halite: a macromolecular target in the search for life on other planets. Astrobiology. 2008 Apr; 8(2):215-28.
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• Baxter BK, Abeliovich H, Zhang X, Stirling AG, Burlingame AL, Goldfarb DS. Atg19p ubiquitination and the cytoplasm to vacuole trafficking pathway in yeast. J Biol Chem. 2005 Nov 25; 280(47):39067-76.
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• Baxter BK, Craig EA. Isolation of UBP3, encoding a de-ubiquitinating enzyme, as a multicopy suppressor of a heat-shock mutant strain of S. cerevisiae. Curr Genet. 1998 Jun; 33(6):412-9.
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• Baxter BK, James P, Evans T, Craig EA. SSI1 encodes a novel Hsp70 of the Saccharomyces cerevisiae endoplasmic reticulum. Mol Cell Biol. 1996 Nov; 16(11):6444-56.
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• Yang CC, Baxter BK, Topal MD. DNA cleavage by NaeI: protein purification, rate-limiting step, and accuracy. Biochemistry. 1994 Dec 13; 33(49):14918-25.
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• Baxter BK, Topal MD. Formation of a cleavasome: enhancer DNA-2 stabilizes an active conformation of NaeI dimer. Biochemistry. 1993 Aug 17; 32(32):8291-8.
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