Major Areas of Research
- Virulence determinants of Cryptococcus neoformans and Aspergillus fumigatus
- Mechanism by which Cryptococcus neoformans invades the brain
- Mechanism by which cryptococci adapt to the brain environment and produce fulminating disease
- The signaling mechanism involved in the cryptococcal adaptation to human brain environment
- The mechanism of cryptococcal adaptive resistance to azole drugs and flucytosine
- Identification of pathobiological differences between Cryptococcus neoformans and its sibling species, Cryptococcus gattii
- Identification of host factors that predispose patients to invasive aspergillosis
The Molecular Microbiology Section is focused on the pathobiology of Cryptococcus neoformans and Aspergillus fumigatus, two of the most common and serious fungal pathogens that primarily affect immunocompromised patients. Both C. neoformans and A. fumigatus are environmental pathogens that cause life-threatening systemic disease upon inhalation. The fatality rate of these diseases is high even if treated with the most effective antimycotic agents currently available.
Cryptococcus neoformans, an environmental yeast species most commonly found in pigeon droppings and soil contaminated with avian guano, is the etiologic agent of cryptococcosis. Cryptococcosis has been recognized as an AIDS-defining disease because the major risk group of the disease is people infected with HIV. Although C. neoformans can cause lesions in almost every organ after being inhaled by the host, the most common clinical manifestation and most common cause of death is meningoencephalitis, an infection of the brain. Cryptococcus gattii, a sibling species of C. neoformans, also causes cryptococcosis but more frequently in otherwise healthy patients without well defined underlying risks. The two species share 85 to 90 percent genomic sequence homology but differ significantly in their ecology, epidemiology, and biochemistry. Our section is currently focusing on their differences in pathobiology as well as the way the host responds to the two pathogens.
Pathogenic Aspergillus species are ubiquitous in our environment, and humans regularly inhale numerous Aspergillus spores (conidia) during daily life. Of those species, Aspergillus fumigatus is known to be the major cause of life-threatening invasive pulmonary aspergillosis (IPA) in immunocompromised patients throughout the world. The major risk for IPA is profound neutropenia and chronic granulomatous diseae (CGD). However, more than 50 percent of CGD patients, as well as neutropenic patients, do not experience IPA in their lifetime. The Molecular Microbiology Section is currently focused on the pathobiological differences between multiple sibling species that belong to Aspergillus sSection Fumigati and host genetic factors that predispose patients to IPA.
Dr. Kwon-Chung received her B.S. and M.S. in biology from Ewha Womans University in Seoul, South Korea, prior to receiving a Fulbright Scholarship to pursue her doctoral work in the bacteriology department at the University of Wisconsin, Madison. After receiving her Ph.D., she joined the Medical Mycology Section of the NIAID Laboratory of Microbiology as a visiting fellow. She became a senior investigator in the NIAID Laboratory of Clinical Investigation in 1973 and has been the chief of the Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, since 1995.
Yun C. Chang, Ph.D.; Ashok Varma, Ph.D; Janyce Sugui, Ph.D.; Michael Davis, Ph.D.; Arpita Singh, Ph.D.; Michael Davis, Ph.D.; Ami Kahanal-Lamichhane, M.S.
Chang YC, Khanal Lamichhane A, Garraffo HM, Walter PJ, Leerkes M, Kwon-Chung KJ. Molecular mechanisms of hypoxic responses via unique roles of Ras1, Cdc24 and Ptp3 in a human fungal pathogen Cryptococcus neoformans. PLoS Genet. 2014 Apr 24;10(4):e1004292.
Saijo T, Chen J, Chen SC, Rosen LB, Yi J, Sorrell TC, Bennett JE, Holland SM, Browne SK, Kwon-Chung KJ. Anti-granulocyte-macrophage colony-stimulating factor autoantibodies are a risk factor for central nervous system infection by Cryptococcus gattii in otherwise immunocompetent patients. MBio. 2014 Mar 18;5(2):e00912-14.
Singh A, Panting RJ, Varma A, Saijo T, Waldron KJ, Jong A, Ngamskulrungroj P, Chang YC, Rutherford JC, Kwon-Chung KJ. Factors required for activation of urease as a virulence determinant in Cryptococcus neoformans. MBio. 2013 May 7;4(3):e00220-13.
Sugui JA, Peterson SW, Clark LP, Nardone G, Folio L, Riedlinger G, Zerbe CS, Shea Y, Henderson CM, Zelazny AM, Holland SM, Kwon-Chung KJ. Aspergillus tanneri sp. nov., a new pathogen that causes invasive disease refractory to antifungal therapy. J Clin Microbiol. 2012 Oct;50(10):3309-17.
Ngamskulrungroj P, Chang Y, Sionov E, Kwon-Chung KJ. The primary target organ of Cryptococcus gattii is different from that ofCryptococcus neoformans in a murine model. MBio. 2012 May 8;3(3). pii: e00103-12.
Lee H, Khanal Lamichhane A, Garraffo HM, Kwon-Chung KJ, Chang YC. Involvement of PDK1, PKC and TOR signalling pathways in basal fluconazole tolerance in Cryptococcus neoformans. Mol Microbiol. 2012 Apr;84(1):130-46.