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Public Health Research Institute Center
UMDNJ - New Jersey Medical School
225 Warren Street
Newark, New Jersey 07103
Phone: (973) 854-3218
Fax: (973) 854-3101
e-mail: xuech@umdnj.edu
 Research Summary
Cryptococcus as a model for host-pathogen interactions
Pathogens adapt to their surroundings or hosts by adjusting cell developmental processes based on changing environmental conditions. Cell surface receptors on pathogens are essential for sensing extracellular signals and controlling intracellular signal transduction pathways that regulate cell development and virulence. My lab studies the human yeast pathogen Cryptococcus neoformans, the casual agent of life-threaten cryptococcal meningitis. C. neoformansis the leading cause of fungal meningitis with over 1 million cases annually in mostly immunocompromised individuals, such as those with HIV/AIDS, organ transplants, or those who are immunocompromised by cancer chemotherapy or by other treatments. As an experimental model organism, Cryptococcus allows us to study how human fungal pathogens sense extracellular signals that are important for their virulence.
1. Functional analysis of G protein-coupled receptors (GPCRs). It is now well established that GPCR signaling is involved in a wide range of physiological processes and diseases, and this family of proteins plays a critical role in sensing extracellular signals. In fact, many proteins in this gene family have been developed as important drug targets for controlling a variety of human diseases. Our studies focus on GPCRs that sense nutrients, and how such interactions affect the regulation of downstream signal pathways, which control the virulence and cellular development of Cryptococcus.
2. Role of inositol and inositol transporters in fungal development and virulence. Inositol is both a basal structural component of cells and an important signaling molecule involved in a variety of cell developmental processes. The C. neoformans genome contains an unusually large inositol transporter gene family that has been found to be important for fungal sexual reproduction and fungal virulence. Our recent studies link fungal inositol acquisition to brain infection in animal models, which correlates with the fact that human and animal brains contain abundant free inositol. We believe that inositol plays a role in the development of cryptococcal meningitis, the predominant and most lethal form of cryptococcosis. An understanding of how inositol is involved in fungal brain infection could have significant impact on understanding of its disease mechanism.
3. Protein ubiquitination and fungal virulence. E3 ubiquitin ligases play an essential role in regulation of many cellular processes, and are considered to be an important new drug target platform for future mechanism-driven drug discovery. We recently identified Fbp1, a key F-box protein of an SCF (Skp1, Cullin, F-box protein) E3 ubiquitin ligase complex, that is essential for C. neoformans to cause disease. We are investigating how this SCFFBP1 E3 ubiquitin ligase is involved in fungal development and fungal virulence, and what are the responsible substrates. We will also extend our study to analyze other F-box proteins in Cryptococcus.
By applying a combination of genetics, biochemistry, and molecular biology, the goal of our research is to gain new insights into fungal-host interactions. The information should lead to novel drug targets, as well as better approaches for diagnosis and control of fungal diseases.
Recent Articles
1. Xue, C., Liu, T., Chen, L., Li, W., Liu, I., Kronstad J.W., Seyfeng, A., and Heitman, J. (2010) Role of an expanded inositol transporter repertoire in Cryptococcus neoformans sexual reproduction and virulence. mBio: 1(1): e00084-10
2. Lin X, Jackson JC, Feretzaki M, Xue C, Heitman J. Transcription factors Mat2 and Znf2 operate cellular circuits orchestrating opposite- and same-sex mating in Cryptococcus neoformans. PLoS Genetics. 2010 6(5):e1000953.
3. Hsueh YP, Xue C, Heitman J. A constitutively active GPCR governs morphogenic transitions in Cryptococcus neoformans. EMBO J. 2009 28(9):1220-33.
4. Xue C, Hsueh YP, Heitman J. Magnificent seven: roles of G protein-coupled receptors in extracellular sensing in fungi. FEMS Microbiology Review. 2008 32(6):1010-32.
5. Xue C, Hsueh YP, Chen L, Heitman J. The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans. Molecular Microbiology. 2008 70(2):379-95.
6. Xue C, Tada Y, Dong X, Heitman J. The human fungal pathogen Cryptococcus can complete its sexual cycle during a pathogenic association with plants. Cell Host Microbe. 2007 1(4):263-73.
7. Bahn YS, Xue C, Idnurm A, Rutherford JC, Heitman J, Cardenas ME. Sensing the environment: lessons from fungi. Nature Review Microbiology. 2007 5(1):57-69.
8. Hsueh YP, Xue C, Heitman J. G protein signaling governing cell fate decisions involves opposing Galpha subunits in Cryptococcus neoformans. Molecular Biology of the Cell. 2007 18(9):3237-49.
9. Park G, Xue C, Zhao X, Kim Y, Orbach M, Xu JR. Multiple upstream signals converge on the adaptor protein Mst50 in Magnaporthe grisea. Plant Cell. 2006 18(10):2822-35.
10. Xue C, Bahn YS, Cox GM, Heitman J. G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. Molecular Biology of the Cell. 2006 17(2):667-79.
Books, monographs and chapters:
1. Xue, C., Wang, Y., and Hsueh, Y. (2010) Assessment of constitutive activity of a G protein-coupled receptor, Cpr2, in Cryptococcus neoformans by heterologous and homologous methods. In Methods in Enzymology (Michael Conn eds.). Elsevier Press. (In press)
2. Alspaugh, J. A., Xue, C., Shen, W.-C., Wang, P. (2009) G-protein signaling athways regulating morphogenesis and virulence of Cryptococcus. In Cryptococcus (Heitman, J., Kozel, T., Kwon-Chung, J., Perfect, J., and Casadevall, A. eds). ASM press, Washington D.C. (In press)
3. Xue, C., Ebbole, D. J., and Heitman, J. (2009) Carbon and amino acid sensing. In Cellular and Molecular Biology of Filamentous Fungi (Borkovich K., Ebbole D., and Momany M. eds). ASM press, Washington, D.C. P469-479
CV:
Zhejiang University, China PhD 2000
Purdue University, Postdoctoral Fellow 2000-2004
Duke University, Postdoctoral Research Associate 2004-2008
PHRI, UMDNJ-New Jersey Medical School, Principal Investigator 2008-present
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Assistant Professor 2008-present
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