Dr. Erin McClelland received a Bachelor of Arts in Aquatic Biology from the University of California, Santa Barbara, and a Ph.D. in Biology under Dr. Wayne Potts from the University of Utah. She completed postdoctoral training under Dr. Arturo Casadevall at Albert Einstein College of Medicine. She was a founding faculty at the Commonwealth Medical College in Scranton, Pennsylvania, where she taught Immunology for four years. She then joined the faculty at Middle Tennessee State University, where she taught microbiology and biotechnology. She is excited to join the faculty at MU-COM to teach Immunology to first- and second-year medical students.
Dr. McClelland comes from a family of teachers and taught both in graduate school and during postdoctoral training, which prepared her for teaching and mentoring students. She is passionate about training students in research, including how to think critically and present their research. Dr. McClelland has mentored >20 undergraduate and graduate students, all of whom have successfully moved on to post-graduate school or postdoctoral training.
Dr. McClelland is a member of the American Association of Immunology and the American Society of Microbiology. She was the KY-TN ASM Branch President from 2018-21. She and her colleagues at MTSU were awarded an NIH R15 grant in 2018 to study how intracellular Cryptococcus neoformans modulates macrophage polarization. The initial results were published in 2020 in PLoS One and the grant is currently submitted for renewal.
I received a Bachelor of Arts in Aquatic Biology from the University of California, Santa Barbara and a Ph.D. in Biology under Dr. Wayne Potts from the University of Utah. I completed postdoctoral training under Dr. Arturo Casadevall at Albert Einstein College of Medicine.
Cryptococcus neoformans (Cn) is a facultative intracellular pathogen that infects most individuals before the age of 5 and establishes decades-long latent infections by residing in host macrophages. If not properly controlled by the immune system, Cn infection results in cryptococcosis, a systemic fungal infection that is lethal if not treated and is the cause of ~181,000 deaths annually. However, serious side effects associated with current treatments and the emergence of new drug-resistant strains present a clear and escalating challenge for the management of cryptococcosis. To meet this challenge and develop new, effective treatments, an improved understanding of how Cn interacts with the immune system is required.
The two major projects in the lab encompass understanding host-Cn interactions: 1) at the level of macrophage polarization and 2) due to the sex of the host. My long-term goals are to better understand host-Cn interactions with macrophages and to explain the role of host sex in the pathogenesis and susceptibility of Cn infections. These goals aim to understand why 70 percent of patients with cryptococcosis are male and may identify sex-specific therapies for patients infected with Cn.
1) The Cn:macrophage interaction is critically important for determining the course and outcome of infections. While macrophages serve as a growth niche for Cn and facilitate the dissemination of Cn from the lungs, they also efficiently clear ingested yeast if polarized to the highly fungicidal M1 state. This state is controlled by STAT1 and NF-κB transcription factors and involves the differential expression of >1000 genes. NF-κB signaling is particularly important in macrophages as a regulator of cell survival and proinflammatory cytokine expression. Over the past decade, we and others have shown that Cn reduces macrophage fungicidal activity and alters host cell NF-κB-dependent gene expression, but the mechanisms regulating this have yet to be elucidated. Previously, we have shown that intracellular Cn infection attenuates the M1 phenotype by altering the transcriptome of host macrophages to more closely match naïve (M0) macrophages. We are currently characterizing how changes in the intracellular Cn transcriptome and virulence factor expression allow Cn to survive within macrophages polarized to the M1 or M2 phenotype.
2) An increasing population of immunocompromised patients has led to a concomitant rise in the incidence of Cn infections, particularly in male AIDS patients. It is currently unknown why male AIDS patients comprise 70% of the patient population with Cn disease, though we have shown that an interaction with testosterone and male macrophages may be involved. The observed contrast in host sex susceptibility suggests a complex interaction of underlying differences in the immune response to Cn infection and differential expression of Cn microbial factors between males and females. My previous studies showed that testosterone induces the release of Cn capsular polysaccharide, its major virulence factor, and that macrophages from males have increased mortality and fungal burden after Cn infection, likely due to the secretion of the growth hormone gibberellic acid in the presence of testosterone, and an impaired immune response to Cn infection in males. These data suggest the interaction of host sex hormones with Cn pathogenesis and possible reasons why males show increased incidence of disease. We are currently characterizing the mechanisms by which testosterone induces secretion of gibberellic acid plan to conduct structure-based drug design to test potential sex-specific antifungals.
Visit Dr. McClellend's My Bibliography page for a complete list of peer-reviewed publications.
Dr. McClelland’s research interests encompass understanding host-pathogen interactions of the pathogenic yeast, Cryptococcus neoformans, including at the level of macrophage polarization and the sex of the host, to try to understand why 70 percent of patients with cryptococcosis are male.
