Professor | Director of the BMI/BMB MS Program
Ph.D. Microbiology, Ohio State University, 1982
Accepting new MS students in 2022: Yes (IM, BMB)
Accepting new PhD students in 2022: No
Vaginal microbiome in health and disease
The vaginal mucosa is composed of perhaps hundreds of bacterial species, many of which have not yet been cultured or identified. These populations shift for unknown reasons, from healthy compositions to those that cause disease such as bacterial vaginosis (BV). Different profiles of species lead to complications ranging from recurrence, failed response to treatment, or risk of pre-term birth. Our project seeks to describe the dynamics of populations as they transition to disease, and to identify species or groups that pose the highest risk for complications, including those that impose greater risks for cervical cancer. We are testing models for causes of the microbial progression from BV to cure to recurrence. We are developing a BV diagnostic and prognostic device.
Extracellular vesicles (EV’s) and a subgroup of these called exosomes are subjects of a relatively new field of study that have cause a rethinking of how cells communicate and promote disease. Cells across all kingdoms generate EV’s, and they play important yet not fully understood roles in cancer progression, infectious diseases, such as tuberculosis, malaria, and mycoses, neurodegenerative disease, and many other areas. Candida, a major fungal pathogen, has recently been shown to generate EV’s with discrete protein and RNA cargo that may influence immune cells and survival in model systems. Their clinical potential for fungal infections is vast, because they may be produced in much larger numbers than the fungal cells themselves, because they likely disseminate to blood, saliva, urine for non-invasive detection, because they may carry RNA or protein cargo that distinguishes colonization from infection and possibly antifungal resistance information, and because they may be engineered to target antifungal therapies or for vaccine development. We are asking which stress conditions generate EV’s, whether they impact on the phenotype of other cells in the population, what protein and RNA cargo they carry, with the goal of defining diagnostic targets, and to begin testing whether vesicles in this fraction can be loaded with antifungals for targeted delivery to fungal cells.
Molecular fungal diagnostics
Fungal infections are prevalent and prone to recurrence (vaginal) or have high morbidity (systemic). Their diagnosis by conventional culture is a problem, due to poor culture efficiency, slow growth rates, and low titer, so that diagnosis often occurs too late for effective treatment. We are developing and are validating molecular tools for their high throughput, quantitative identification directly from samples.
Antifungal drug resistance in Candida albicans
This opportunistic yeast pathogen is resourceful and diverse in finding ways to evade inhibition by antifungal agents. These include mutation in target genes, mutational or regulatory activation of target and compensatory pathways, drug efflux, and unknown mechanisms. We are looking at mechanism by which this yeast induces high frequency loss of heterozygosity as an adaptive mechanism. We developed an overexpression system for identification of genes that alter antifungal susceptibility and are inventorying these genes and their effects by RT-qPCR and microarray.
Mitochondrial responses to antifungal stress
Candida albicans is typically unable to survive without its mitochondrial genome and functions, unlike S. cerevisiae. We have initiated a new project that examines how mitochondrial copy number and genome integrity changes in response to antifungal and other stresses, and whether this response plays a role in tolerance and persistence and represents a potentially new target of next generation antifungals.