University at Buffalo
The Witebsky Center

The Witebsky Center
University at Buffalo
Bacteriology Host-Microbe Interactions Immunology Parasitology Virology
The Witebsky Center The Witebsky Center
John C. Panepinto
John C. Panepinto, Ph.D.
Assistant Professor
Department of Microbiology and Immunology
School of Medicine and Biomedical Sciences
University at Buffalo
117 Biomedical Research Building
Buffalo, NY 14214
(716) 829-2090


The basidiomycetous fungus Cryptococcus neoformans is the causative agent of life-threatening meningo-encephalitis in patients with defects in cell-mediated immunity, and an immune reconstitution syndrome in HIV+ patients beginning intensive antiretroviral therapy. The need for continued research into understanding the pathogenic mechanisms employed by this organism is evident as C. neoformans has become the most common cause of community acquired meningitis in areas of Africa and Southeast Asia plagued by the HIV pandemic.

The focus of my laboratory is to investigate mechanisms by which C. neoformans adapts to the environment of the host.  Our current line of investigation is assessing the role of post-transcriptional gene regulation, i.e. mRNA degradation, in the adaptation of C. neoformans to host temperature and to replication stress.

A targeted gene knockout strain of C. neoformans lacking the mRNA deadenylase Ccr4 is defective in host-temperature adaptation.  Using microarray analysis under conditions of transcriptional shutoff, we are able to determine the specific transcripts that are stabilized and destabilized in response to particular stresses, such as host temperature.  In addition, we are using the ccr4D strain as a tool to understand the upstream signaling mechanisms that lead to the engagement of the mRNA degradation machinery in response to stress, and the cellular processes that require modulation by this mechanism to allow successful adaptation to the host environment and subsequent disease.  Elucidating the mechanisms required for adaptation of C. neoformans to the host environment will increase our inventory of potential targets for novel anti-cryptococcal and anti-fungal therapies.

Selected Publications:

Hu G, Hacham M, Waterman SR, Panepinto J, Shin S, Liu X, Gibbons J, Valyi-Nagy T, Obara K, Jaffe HA, Ohsumi Y, Williamson PR. PI3K signaling of autophagy is required for starvation tolerance and virulence of Cryptococcus neoformans. J Clin Invest. 2008 Mar;118(3):1186-97.

Panepinto JC, Komperda KW, Hacham M, Shin S, Liu X, Williamson PR. Binding of serum mannan binding lectin to a cell integrity-defective Cryptococcus neoformans ccr4D mutant.  Infect Immun. 2007 Oct;75(10):4769-79. Epub 2007 Jul 23.

Waterman SR, Hacham M, Hu G, Zhu X, Park YD, Shin S, Panepinto J, Valyi-Nagy T, Beam C, Husain S, Singh N, Williamson PR. Role of a CUF1/CTR4 copper regulatory axis in the virulence of Cryptococcus neoformans. J Clin Invest. 2007 Mar;117(3):794-802. Epub 2007 Feb 8.

Waterman SR, Hacham M, Panepinto J, Hu G, Shin S, Williamson PR. Cell wall targeting of laccase of Cryptococcus neoformans during infection of mice. Infect Immun. 2007 Feb;75(2):714-22. Epub 2006 Nov 13.

Zhang S, Hacham M, Panepinto J, Hu G, Shin S, Zhu X, Williamson PR. The Hsp70 member, Ssa1, acts as a DNA-binding transcriptional co-activator of laccase in Cryptococcus neoformans. Mol Microbiol. 2006 Nov;62(4):1090-101. Epub 2006 Oct 16.
Liu X, Hu G, Panepinto J, Williamson PR. Role of a VPS41 homologue in starvation response, intracellular survival and virulence of Cryptococcus neoformans. Mol Microbiol. 2006 Sep;61(5):1132-46.

Zhao W, Panepinto JC, Fortwendel JR, Fox L, Oliver BG, Askew DS, Rhodes JC. Deletion of the regulatory subunit of protein kinase A in Aspergillus fumigatus alters morphology, sensitivity to oxidative damage, and virulence. Infect Immun. 2006 Aug;74(8):4865-74.

Panepinto JC, Williamson PR. Intersection of fungal fitness and virulence in Cryptococcus neoformans.
FEMS Yeast Res. 2006 Jun;6(4):489-98. Review.

Panepinto J, Liu L, Ramos J, Zhu X, Valyi-Nagy T, Eksi S, Fu J, Jaffe HA, Wickes B, Williamson PR.
The DEAD-box RNA helicase Vad1 regulates multiple virulence-associated genes in Cryptococcus neoformans. J Clin Invest. 2005 Mar;115(3):632-41.

Panepinto JC, Oliver BG, Fortwendel JR, Smith DL, Askew DS, Rhodes JC. Deletion of the Aspergillus fumigatus gene encoding the Ras-related protein RhbA reduces virulence in a model of Invasive pulmonary aspergillosis. Infect Immun. 2003 May;71(5):2819-26.

Panepinto JC, Oliver BG, Amlung TW, Askew DS, Rhodes JC. Expression of the Aspergillus fumigatus rheb homologue, rhbA, is induced by nitrogen starvation. Fungal Genet Biol. 2002 Aug;36(3):207-14.