Angela Gelli, Ph.D.

Education:

• University of Toronto, Canada, PhD Cell Biology and Electrophisiology, 1997
• University of Toronto, Canada, MSc Electrophisiology, 1992
• University of Toronto, Canada, BSc Chemistry and Biochemistry, 1990

Department: Pharmacology
Research Interests:

Virulence determinants of fungal pathogenesis, Molecular Pharmacology

Research Summary:

My lab studies the pathogenesis of human fungal pathogens with a focus on Cryptococcus neoformans - the leading cause of fungal meningoencephalitis. For the past several years we have focused on the activation and regulation of a plasma membrane calcium channel in fungal cells and its potential use as a therapeutic target. Our NIH funded research program is currently focused on a high-throughput small molecule and off-patent drug screen to identify specific blockers of the channel and assess their therapeutic potential for the treatment of cryptococcal infection. We use a multidisciplinary approach that includes electrophysiology, imaging, cell biology, animal models, and molecular biology to validate the hits identified in our screen and test their ability to clear cryptococcal infections in vivo. Recently we have also become very interested in resolving the molecular mechanisms that facilitate the invasion of C. neoformans into the central nervous system. This interest was spearheaded in part by our study of the extracellular proteome of C. neoformans where we found that many of these secreted proteins are proteases and likely play a role in mediating fungal-host interactions. We have since developed an in vitro model of the blood-brain barrier and we have shown that it is a very useful system for defining the mechanisms of cryptococcal invasion into the CNS. Our aim is to characterize a key protease that cryptococcal cells require to breach the blood-brain barrier and enter the brain parenchyma. Our immediate goal will be to screen for inhibitors of this protease and test in the murine model of cryptococcal meningitis whether these inhibitors can prevent brain infections. The long-term goal will be to assess whether this key protease can be engineered to facilitate the movement of crucial drugs (whether they be to treat brain tumors or neurodegenerative diseases) across the blood-brain barrier.

Courses/Teaching:

• PHA 400 Principles of Pharmacology Winter
• PTX 203 Integrated physiological systems, cardiovascular, reproductive, immune and nervous system. Spring
• FRS 003 Bad bugs and few drugs: Infectious Diseases in the 21st Century. Winter

Lab Members:

Mike Hong, Postdoctoral researcher; Kiem Vu and Jennifer Bautos, Graduate Students; Rick Tham, Junior Specialist; SoYoung Park, Visiting Scholar; Danielle Huffman, Undergraduate Student

Lab Rotation Availability: Yes
PubMed listing