Lecturer in Eukaryotic Microbiology
1.) The acute innate immune responses and the role of early granuloma formation in the containment of this fungal infection in vivo. We are using zebrafish larvae to understand acute immune responses to fungal spore that enable protection from disease as well as decipher the changes in susceptible hosts that allow spore dissemination and disease onset.
2.) The cellular interactions between fungal spores and innate immune effectors. Specifically, we aim to understand the cellular and molecular changes that alter the innate immune response ineffective to spores both in healthy (i.e. lack of spore killing) and susceptible hosts. For example, we recently discovered a novel secreted fungal metabolite that interferes with phagocyte functions. We are now characterising this compound chemically as well as evaluating its biological function(s) and potential pharmacological potential.
3.) The molecular mechanisms of spore germination, the developmental process underlying formation of invasive hyphae and thus onset of disease. Specifically, we are using germination inhibitors, that we identified within a natural compound library, to characterise the genetic control of onset of germination as well as the mechanism of inhibition.
Mucormycosis is an opportunistic fungal infection with extremely high mortality rates (>90%). Disease is caused by a spectrum of species belonging to the Mucorales (e.g. Rhizopus oryzae, Mucor circinelloides, Lichtheimia corymbifera). Advances in medical care and an aging population have resulted in a recent rise in the incidence of this fungal infection, such that mucormycosis is now the second most prevalent mould infection worldwide. Recent data from France show an increase of 7.3% in the incidence and 9.3% in the mortality rate of mucormycosis cases between 2001-2010. In addition, reports of mucormycosis outbreaks have become increasingly frequent: in September 2013 200 patients in the US presented with foodborne mucormycosis; 13 mucormycosis cases occurred after tornado Joplin in 2011 and 16 cases of invasive mould infection by Mucorales following combat-related injuries in US soldiers serving in Afghanistan were reported in 2010.
Treatment of mucormycosis is very costly, with an average expense of $100,000 per case, but remains unsuccessful in most cases. Current antifungal therapy for mucormycosis is ineffective and highly toxic; treatment involves extensive surgical removal of infected tissue, often leading to limb amputation and long-term disability. Thus, there is a clear need to develop new therapeutic approaches.
Traditionally, attempts to decipher and intervene with mucormycosis pathogenesis have focused on later stages of infection when the fungus interacts with epithelial layers. However, my lab uniquely aims to elucidate the early stages of infection in order to mediate the events that lead to invasive establishment of disease. In the long-term we aim to identify new treatment approaches targeting the host-pathogen interface during acute infection.
Voelz, K., R. L. Gratacap and R. T. Wheeler (2015). A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides. Disease Models and Mechanisms 8 (11), 1375-1388.
Trzaska W. J., J. N. Correia, M. T. Villegas, R. C. May and K. Voelz (2015). pH manipulation as a novel strategy for treating highly anti-fungal resistant mucormycosis. Antimicrobial Agents and Chemotherapy 59 (11), 6968-6974.
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 a019562.
University of Birmingham
School of Biosciences
Phone: +44 (0)121 4145572