Interdisciplinary PhD in Molecular Biosciences

Dr. Erin McClelland - Research Interests

Understanding the interplay between hosts and pathogens is vitally important for rational design of treatment for microbial infections and diseases. I am particularly interested in immunology, microbial pathogenesis, the problem of evolution of virulence and identifying factors that are associated with virulence, from both the host and microbial perspectives. To study evolution-related & host-pathogen interaction questions, I utilize the pathogenic & medically relevant fungus Cryptococcus neoformans. C. neoformans infects a wide variety of hosts and causes cryptococcosis, a common opportunistic infection in AIDS patients which results in fungal meningitis.

Current Research Projects:

1. Determine whether gender-associated differences in the immune response are responsible for gender-related differences in susceptibility to C. neoformans

One of the more interesting aspects of C. neoformans infections is the large discrepancy in the incidence of infections in male and female patients, with males having a higher incidence of C. neoformans infection and disease than females. This gender-related difference has been observed in dozens of studies and suggests underlying differences in the interactions of the immune response to C. neoformans infection and differential expression of microbial factors between males and females. We have found differences in the immune response of ex vivo male or female macrophages to C. neoformans, which was recently published in PLoS One. Currently, we are characterizing gender-specific and microbial factors in clinical isolates to determine which are involved in the gender susceptibility difference to C. neoformans.

2. Determine factors involved in C. neoformans pathogenesis and evolution of virulence.

The ability of C. neoformans to infect a broad range of hosts, including immunocompetent individuals, makes the study of its virulence mechanisms & host interactions crucial for much needed therapies. Does C. neoformans change its virulence factors to cause disease in such a large variety of hosts? Does the host immune response help or hinder virulence? Are there host-specific factors that contribute to C. neoformans virulence? There are currently no data as to the type of mechanism that C. neoformans may use to evolve virulence. Identification of such mechanisms could expose new virulence factors and important characteristics of C. neoformans pathogenesis. We have identified a transcription factor that is involved in virulence in mice and are currently characterizing its function to determine how it affects pathogenesis. This is an ideal project for a graduate student.

3. Determine factors involved in C. neoformans intracellular replication.

One of the major virulence factors of C. neoformans is its ability to survive and replicate within phagocytic cells. It is thought that this is one way in which C. neoformans escapes the immune response and disseminates throughout the host. Understanding the mechanism behind intracellular replication could identify new microbial factors related to C. neoformans virulence and lead to new therapeutics for treatment of cryptococcosis. The wax worm larvae Galleria mellonella is an excellent invertebrate host model for C. neoformans infections because it contains phagocytic hemocytes that have been shown to phagocytose C. neoformans, which, in turn, has been shown to replicate within hemocytes. We created a strain of C. neoformans that was passaged in G. mellonella for 100 C. neoformans generations. This strain shows significant phenotypic differences in various C. neoformans virulence factors and kills mice significantly faster than the prepassaged strain, through both intratracheal and intravenous routes of infection. We are currently working to characterize the microbial factors that are responsible for the increased virulence and hope to find the gene(s) or factor(s) involved in intracellular replication.

Thus, most of the projects in the laboratory encompass microbial pathogenesis, the evolution of virulence, host-pathogen interactions and the immune response to C. neoformans infection.

I am always interested in talking to prospective graduate and undergraduate students about working in the lab.