The Voelz lab is interested in host-pathogen interactions. The lab's current research programme aims to significantly improve our understanding of the innate immune response during a fungal disease called mucormycosis in order to highlight immunomodulatory strategies to harness the host's immune system to improve patient outcomes. Dr Voelz's group uses an in vivo zebrafish larval model to investigate the interaction of infectious fungal spores with the host's innate immune system.
Mucormycosis is an emerging and clinically difficult to manage fungal infection with increasing incidence and extremely high mortality rates. Individuals with diabetes, suppressed immunity or traumatic injury are at particular risk of developing disease. These patients oeen present with defects in innate immunity, especially phagocytic effector cell function. However, lifle research on the innate immune response during mucormycosis has been conducted to date.
Traditional animal models do not provide insights into the cellular interactions between pathogens and host cells (e.g. immune effector cells). In recent years, the zebrafish model, Danio rerio, has become an accepted model system for the study of infectious diseases. The Voelz lab has recently established a zebrafish larval model for mucormycosis to study the molecular pathogenesis mechanisms involved in this fungal disease. The lab now uses the transparent larvae to examine the interaction between the host and fungal spores on a cellular level across the whole animal by microscopic real- time studies.
The lab is particularly interested in the following aspects of the interaction between fungal spores and the host innate immune system:
Interaction with phagocytes
The mechanism of spore uptake by phagocytes is currently unknown. The lab aims to characterize the receptors and mechanisms involved in recognition of fungal spores by phagocytic effector cells. Aeer phagocytic uptake phagosomes undergo a sequential maturation process that gradually creates a more and more inhospitable environment within the phagosome and usually culminates in microbial digestion. However, preliminary data show that that zygomycete spores are readily taken up by phagocyte but macrophages fail to digest spores and to induce a strong immunogenic response. Therefore, the lab endeavors to elucidate the phagocyte maturation process aeer uptake of fungal spore as well as the innate immune signaling response to fungal spores.
In healthy individuals, phagocytes efficiently inhibit spore germination and failure to inhibit spore germination is a major aspect of onset of mucormycosis. At the same time, initiation of spore germination requires appropriate regulation of gene expression. Hence, we are interested in the gene expression patterns during germination.
L. Mendoza, R. Vilela, K. Voelz, A. S. Ibrahim, K. Voigt, S. C. Lee (2014) Chapter 27. Human Fungal Pathogens of Mucorales and Entomophthorales. Human Fungal Pathogens Cold Spring Harbor Perspectives.
Voelz K., H. Ma, E. J. Byrnes, S. Phadke, P. Zhu, R. A. Farrer, D. A. Henk, Y. Lewit, Y.- P.Hsueh, M. C. Fisher, A. Idnurm, J. Heitman, R. C. May (2013) Transmission of hypervirulence traits via sexual reproduction within and between lineages of the human fungal pathogen Cryptococcus gattii. PLoS Genetics 9:e1003771.
Hagen F., P.C. Ceresini, I. Polacheck, H. Ma, F. van Nieuwerburgh, T. Gabaldon, S. Kagan, E. R. Pursall, H. L. Hoogveld, L. J. J. van Iersel, G. W. Klau, S. M. Kelk, L. Stougie, K. H. Bartlett, K. Voelz, L. P. Pryszcz, E. Castaneda, M. Lazera, W. Mayer, D. Deforce, J. F. Meis, R. C. May, C. H. W. Klaassen, T. Boekhout (2013) Ancient dispersal of the human fungal pathogen Cryptococcus gattii from the Amazon rainforest. PLoS One 8:e71148.
Byrnes E. J. 3rd, W. Li, P. Ren, Y. Lewit, K. Voelz, J. A. Fraser, F. S. Dietrich, R. C. May, S. Chatuverdi, V. Chatuverdi, J. Heitman. 2011. A Diverse Population of Cryptococcus gattii Molecular Type VGIII in Southern Californian HIV/AIDS Patients. PLoS Pathog 7: e1002205.
Voelz, K., S. A. Johnston, J. C. Rutherford, and R. C. May. 2010. Automated Analysis of Cryptococcal Macrophage Parasitism Using GFPTagged Cryptococci. PLoS ONE 5:e15968.
Byrnes, E. J., 3rd, W. Li, Y. Lewit, H. Ma, K. Voelz, P. Ren, D. A. Carter, V. Chaturvedi, R.J. Bildfell, R. C. May, and J. Heitman. 2010. Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States. PLoS Pathog 6:e1000850.
Voelz, K., S. A. Johnston, and R. C. May. 2010. Intracellular replication and exit strategies.J. Heitman, T. R. Kozel, K. J. Kwon-Chung, J. R. Perfect, and A. Casadevall (ed.), Cryptococcus: from human pathogen to model yeast. ASM press, Washington DC.
Voelz, K., and R. C. May. 2010. Cryptococcal interactions with the host immune system. Eukaryot Cell 9:835-846.
Voelz, K., D. A. Lammas, and R. C. May. 2009. Cytokine signaling regulates the outcome of intracellular macrophage parasitism by Cryptococcus neoformans. Infect Immun. 77: 3450-3457.
Burmester, A., M. Richter, K. Schultze, K. Voelz, D. Schachtschabel, W. Boland, J.Wostemeyer, and C. Schimek. 2007. Cleavage of betacarotene as the first step in sexual hormone synthesis in zygomycetes is mediated by a trisporic acid regulated beta-carotene oxygenase. Fungal Genet Biol 44:1096-1108.