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Assistant Professor Molecular Biology and Microbiology Division Dept. of Biological Sciences |
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Assistant Professor Molecular Biology and Microbiology Division Dept. of Biological Sciences |
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My research interests broadly encompass the molecular and cellular biology of medically important fungi. Succinctly stated, I am a molecular medical mycologist. I am especially curious about fungal virulence factors, geneexpression patterns during cellular development, drug resistance, the discoveryof novel antifungal targets, and the epidemiology of mycoses (fungal infections).I also maintain an interest in antifungal susceptibility testing and thehistopathological diagnosis of fungal diseases.
Currently, my primary research interest focuses upon the molecular mechanisms involved in the dimorphism of pathogenic fungus, Penicillium marneffei .During the last decade, this fungus has emerged as a very significant opportunistic pathogen of humans living in Southeast Asia, particularly those who areHIV positive. So prominent are infections by this fungus that the isolationof this pathogen from afflicted individuals is now considered an AIDS-indicator disease.
When isolated from nature, P. marneffei grows as a mould comprised of hyphae (filamentous cells). It is upon these hyphae that reproductiveconidia ("spores") are borne. When inhaled, hyphal fragments or conidiaare phagocytized. These cells subsequently undergo a phenotypic change,termed "phase transition." This change is marked by the formation of yeast-likecells are better defined as arthroconidia, in strict mycological jargon.Once formed, the arthroconidia continue to grow and thrive within the hostcell environment which is thefocal point of disseminated disease causedby P. marneffei.
Phase transition is considered requisite for the pathogenesisof P. marneffei. Like many other fungal pathogens, phase transitionin P. marneffei is a thermally regulated process that is easilymimickedin the laboratory. In vitro incubation of hyphae or conidia at25°C results in the development of the mould form, whereas arthroconidiaarise at 37°C. Hence, those genes relevant to dimorphism can be morereadily studied from simple temperature shifts. Moreover, phase transitionis entirely reversible by a reciprocal shift of incubation temperature.This latter observation implies that the underlying morphogenic mechanismsare strictly regulated by the expression of phase-specific genes. Sinceformation of arthroconidia is essential topathogenesis, it is conceivablethat phase-specific genes contribute to theoverall virulence of P.marneffei.
My laboratory has identified several candidate phase-specific genesin P. marneffei using the novel molecular methodology known as differential display. Some of these genes are solely expressed duringthe mould phase,whereas others are specific to arthroconidial development.Quite interestingly,two of these arthroconidial-specific genes encodethe key enzymes of the glyoxylate cycle. This biochemical pathway, whichis only found in microbes and plants, helps replenish intermediates ofthe Krebs cycle as they are consumed. Recent evidence suggests that thispathway may promote the survival of the tuberculosis agent, Mycobacteriumtuberculosis, in macrophages following phagocytosis. If the same istrue of P. marneffei, then the enzymes of the glyoxylate cycle maynot only represent virulence factors, but also attractive targets for thedevelopment of novel antifungal agents. Studies are currently underway to assess the role of these genes in dimorphism and virulence.
Penicillium marneffei Research
COOPER C.R. Jr., Haycocks N.G. Penicillium marneffei: an insurgent species among the penicillia. Journal of Eukaryotic Microbiology 47: 24-28, 2000.
Nelson K.E., Kaufman L., COOPER C.R., Merz W.G. Penicillium marneffei :infection and biology. Infections in Medicine 16:118-121, 128, 1999.
COOPER C.R, Jr. From bamboo rats to humans: the odyssey of Penicillium marneffei. ASM News 64: 390-397, 1998.
COOPER C.R. Jr., McGinnis M.R. Penicillium marneffei, an emerging acquired immunodeficiency syndrome-related pathogen. Archives of Pathology and Laboratory Medicine 121:798-804, 1997.
Vanittanakom N., COOPER C.R. Jr., Chariyalertsak S., Youngchim S., Nelson K.E., Sirisanthana T. Restriction endonuclease analysis of Penicillium marneffei. Journal of Clinical Microbiology 34:1834-1836, 1996.
Supparatpinyo E., Nelson K.E., Merz W.G., Breslin B.J., COOPER C.R.Jr., Sirisanthana T. Response to antifungal therapy by human immunodeficiencyvirus-infected patients with disseminated Penicillium marneffei.Infections and in vitro susceptibilities of isolates from clinical specimens.Antimicrob Agents Chemother 37:2407-2411, 1993.
Other Selected Publications
Haubold E.M., COOPER C.R. Jr., Wen J.W., McGinnis M.R., Cowan D.F. Comparative morphology of Lacazia loboi (syn. Loboa loboi) in dolphinsand humans. Medical Mycology 38: 9-14, 2000
Haubold E.M., Aronson J.F., Cowan D.F., McGinnis M.R., COOPER C.R. Jr. Isolation of fungal rDNA from bottlenose dolphin skin infected with Loboa loboi. Medical Mycology 36: 263-267, 1998.
COOPER C.R. Jr., McGinnis M.R. In vitro susceptibility of clinical yeast isolates to fluconazole and terconazole. American Journal of Obstetricsand Gynecology 176:1626-1631, 1996.
Peng M., COOPER C.R. Jr., Szaniszlo P.J. Genetic transformation of the dematiaceous phaeohyphomycotic fungus Wangiella dermatitidis. Applied Microbiology and Biotechnology 44:440-450, 1995.
COOPER C.R. Jr., Szaniszlo P.J. Evidence for two cell division cycle( CDC) genes that govern yeast bud emergence in the pathogenic fungus Wangiella dermatitidis. Infection and Immunity 61:2069-2081, 1993.
