Cheryl A. Gale, MD
Yeast molecular genetics, PCR-mediated epitope tagging gene disruption, fluorescence microscopy, time-lapse video microscopy
The Gale laboratory studies the molecular mechanisms of morphogenesis in the opportunistic fungal pathogen, Candida albicans. C. albicans is the leading cause of invasive fungal disease in immunocompromised patients, especially premature infants, the patient population that Dr. Gale (a neonatologist) is particularly interested in. The pathogenesis of C. albicans infections is associated with the ability to change the morphogenesis program from budding yeast-form growth to filamentous, hyphal-form growth. C. albicans strains that are unable to make the transition between these morphogenesis programs are less virulent in animal- and tissue-based models of candidiasis. In addition, hyphae exhibit tropisms (the ability to change the direction of growth in response to environmental stimuli) and these are proposed to facilitate tissue penetration and invasion during the pathogenesis process.
The Gale laboratory uses molecular and cell biological approaches to dissect the differences that underlie yeast- and hyphal-form growth and to understand how the filamentous hypha, in particular, facilitates tissue invasion. Specific research projects involve identifying and characterizing the role of hyphal tip-localized polarity proteins in morphogenesis, growth tropisms, and tissue invasion and virulence using in vitro tissue culture models as well as in vivo models of candidiasis. In addition, we have developed a set of vectors that allow PCR-mediated construction of green, yellow, or cyan fluorescent protein fusions that facilitate the monitoring of protein co-localization and expression in C. albicans in real time. Using this tool, we are characterizing the temporal and spatial localization requirements of polarity proteins throughout the cell cycle, during the transition between morphologic forms, and with alteration in hyphal growth direction.
Gale CA, Leonard MD, Finley KR, Christensen L, McClellan M, Abbey D, Kurischko C, Bensen E, Tzafrir I, Kauffman S, Becker J, Berman J. Microbiology. 2009 SLA2 mutations cause SWE1-mediated cell cycle phenotypes in Candida albicans and Saccharomyces cerevisiae. Dec;155(Pt 12):3847-59. Epub 2009 Sep 24.
Brand A, Vacharaksa A, Bendel C, Norton J, Haynes P, Henry-Stanley M, Wells C, Ross K, Gow N.A.R, Gale C. A. An Internal Polarity Landmark is Important for Externally Induced Hyphal Behaviors in Candida albicans. Eukaryotic Cell 2008 7: 712-720.
Crampin H, Finley K, Gerami-Nejad M, Court H, Gale C, Berman J, and Sudbery P. Candida albicans hyphae have a Spitzenkörper that is distinct from the polarisome found in yeast and pseudohyphae. Journal of Cell Science 118: 2935-2947, 2005.
Hausauer D, Gerami-Nejad M, Kistler-Anderson C, and Gale C. Hyphal guidance and invasive growth in Candida albicans require the Ras-like GTPase Rsr1p and its GTPase activating protein Bud2p. Eukaryotic Cell, 4:1273-1286, 2005.
Lee S, Khalique Z, Gale C, and Wong B. Intracellular trafficking of fluorescently tagged proteins associated with pathogenesis in Candida albicans. Medical Mycology 43: 423-430, 2005.
Prill SKH, Klinkert B, Timpel C, Gale C, Schroppel K, Ernst J. PMT gene family of Candida albicans: five isoforms of protein mannosyltransferase regulate growth, morphogenesis and antifungal resistance. Molecular Microbiology 55: 546-560, 2005.
Gerami-Nejad M, Hausauer D, Berman J, Gale C. Cassettes for the PCR-mediated construction of regulatable alleles in Candida albicans. Yeast 21: 429-436, 2004.
Davis D, Gale C, Berman J, Magee P. Molecular biological and genomic approaches to the study of medically important fungi. Infection and Immunity 71:2299-2309, 2003.
Gale C, Gerami-Nejad M, McClellan M, Vandoninck S, Longtine MS, Berman J. Candida albicans Int1p interacts with the septin ring in yeast and hyphal cells. Molecular Biology of the Cell 12:3536-3549, 2001.
Gerami-Nejad M, Berman J, Gale C. Cassettes for PCR-mediated construction of green, yellow, and cyan fluorescent protein fusions in Candida albicans. Yeast 18:859-864, 2001.
Asleson C, Bensen E, Gale C, Melms A-S, Kurischko C, Berman J. Candida albicans INT1-induced filamentation in Saccharomyces cerevisiae depends on Sla2p. Molecular and Cellular Biology 21:1272-1284, 2001.
Gale C, Bendel C, McClellan M, Hauser M, Becker J, Berman J, Hostetter M. Linkage of adhesion, filamentous growth, and virulence in Candida albicans to a single gene, INT1. Science 279:1355-1358, 1998.
Gale CA, Finkel D, Tao N-J, Meinke M, McClellan M, Olson J, Kendrick K, Hostetter MK. Cloning and expression of a gene encoding an integrin-like protein in Candida albicans. Proceedings of the National Academy of Sciences, USA. 95:357-361, 1996.
D136 May and 6-124 MCB
Filamentous hyphae emanating from the edge of a Candida albicans colony
Fluorescent fusion protein technology used to study protein co-localization