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 fungal pathogen Cryptococcus neoformans, which causes pneumonia and cryptococcal meningitis in immunocompromised individuals, such as those with HIV/AIDS, and accounts for nearly 1 million deaths worldwide. As an experimental model organism, Cryptococcus allows us to study how human fungal pathogens sense signals that are important for their virulence. It is now well established that G-protein-coupled receptor (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 the interactions between extracellular signals and GPCRs, and how such interactions affect the regulation of downstream signal pathways, which control the virulence and cellular development of Cryptococcus. One important molecule in this process is inositol, which is both a basal structural component of cells, as well as an important signaling molecule involved in a variety of cell developmental processes. Recently, insoitol was identified as an important factor for mating and sporulation of Cryptococcus, which influences virulence. Our research focus in this area is to understand how inositol is involved in the mating and potential infectivity of 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

Hsueh YP, Xue C, Heitman J. (2009)
A constitutively active GPCR governs morphogenic transitions in Cryptococcus neoformans.
EMBO Journal 28: 1220-1233.

Xue, C., Ebbole, D. J., and Heitman, J. (2008)
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. (Invited book chapter, in press)

Xue, C., Hsueh, Y., and Heitman, J. (2008)
Magnificent seven: roles of G protein coupled receptors in extracellular sensing in fungi.
FEMS Microbiology Reviews, 32: 1010-1032.

Xue, C., Hsueh, Y., Chen, L., and Heitman, J. (2008)
The RGS protein Crg2 regulates both pheromone and cAMP signaling in the AIDS-associated fungal pathogen Cryptococcus neoformans.
Molecular Microbiology, 70: 379-395.

Xue, C., Tada, Y., Dong, X., and Heitman, J. (2007)
The human fungal pathogen Cryptococcus can complete its sexual cycle during a pathogenic association with plants.
Cell Host & Microbe, 1:263-273.

Hsueh, Y., Xue, C., and Heitman, J. (2007)
G protein signaling governing cell fate decisions involve opposing G( subunits in Cryptococcus neoformans.
Molecular Biology of the Cell, 18: 3237-3249.

Bahn, Y., Xue, C., Idnurm, A., Rutherford, J. C., Heitman, J., and Cardenas, M. E. (2007)
Sensing the environment: lesions from fungi.
Nature Reviews Microbiology 5: 57-69.

Xue, C., Bahn, Y., Cox, G. M., and Heitman, J. (2006)
G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans.
Molecular Biology of the Cell 17: 667-679.