Host-pathogen interactions in CNS infection: Resolving cellular and molecular mechanisms of invasion and BBB function during pathological conditions.
The Gelli Lab studies the pathogenesis of human fungal pathogens with a particular focus on fungi that disseminate to the central nervous system (CNS). Among the pathogens we study is Cryptococcus neoformans - the leading cause of fungal meningoencephalitis. Our studies are aimed at resolving the molecular mechanisms mediating the interplay between fungi and the CNS. This interest was spearheaded in part by our study of the extracellular proteome of C. neoformans, where we identified a key fungal protease that promotes fungal disease in the CNS. Current studies include translation of our basic research to develop anti-virulence drugs via drug screens aimed at blocking protease activity and developing a platform technology that will deliver therapeutic drugs across the blood-brain barrier (BBB) by conjugating the protease to drug-loaded nanocarriers.
Our current research efforts include collaborative studies aimed at the characterization of a similar protease in the pulmonary-to-CNS dissemination of Coccidioides, the cause of Valley Fever throughout the Southwestern United States, and a novel diagnostic tool that would differentiate a pulmonary cancer nodule from a fungal nodule.
Our interest in the BBB during pathological conditions has resulted in a collaborative study aimed at understanding how endothelial cell senescence during aging alters BBB function and how that impacts the onset of dementia and Alzheimer’s disease.
Ph.D., University of Toronto, Ontario, Canada 1997
B.Sc., University of Toronto, Ontario, Canada 1990
M.Sc., Electrophysiology, University of Toronto, Ontario, 1992
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, 1997-2000
Honors and Awards
NSERC Post-Doctoral Scholar, (Natural Science and Engineering Research Council of Canada), 1998
Finalist, Burroughs Wellcome Scholar – Infectious Disease, 2016
UC Davis Research Travel Award – Invited Symposium Speaker, 7th International, Conference Cryptococcus & Cryptococcosis, Nagasaki Japan, 2008
ID Week 2012TM Program Committee Choice Award, Infectious Diseases Society of America – 50th Annual Infectious Disease Society of America (IDSA) Meeting - San Diego CA, 2012
Hartwell Investigator, Biomedical Research Award, The Hartwell Foundation, 2013
Published article (MBio, 2014) selected for Faculty1000Prime, 2014
Elected, Councilor West for Medical Mycologists Society of the Americas, MMSA, 2015
Selected, Top Women-led Technology Companies, Sacramento CA, Fourth Wave, 2017
Select Recent Publications
Aaron PA, Jamklang M, Uhrig, JP, Gelli A. The blood-brain barrier internalizes Cryptococcus neoformans via the EphA2-tyrosine kinase receptor. Cellular Microbiology. 2018
Na Pombjra S, M Salemi, Phinney BS, Gelli A. The metalloprotease, Mpr1, engages AnnexinA2 to promote the transcytosis of fungal cells across the blood-brain barrier. Frontiers Cell and Infection Microbiology. 2017 June.
Gelli, A. Cryptococcus gattii clinical isolates is indirectly mediated by the FCY2-FCY1-FUR1 pathway. Medical Mycology. (In press, MM-2017-0159.R2)
Gelli A. Exploiting fungal mechanisms to breach the blood-brain barrier. Research Features Magazine – Neuroscience. 2016;issue: 103:24-27.
Yang ML, Uhrig JP, Vu K, Singapuri A, Dennis M, Gelli A, & Thompson GR III. Fluconazole susceptibility in Cryptococcus gattii is dependent on the ATP binding cassette (ABC) transporter PDR11. Antimicrobial Agents & Chemotherapy. 2016;60(3):1202-1207
Vu K, Tham, R, Thompson III, G.M., Bautos, J.M., Uhrig, J, and Gelli A. Invasion of the Central nervous system by Cryptococcus neoformans requires a secreted fungal metalloprotease. MBio. 2014;5(3)e01101-14
Vu K, Weksler B, Romero I, Couraud PO, Gelli A. An immortalized human brain endothelial cell line HCMEC/D3, as a model of the blood-brain barrier facilitates in vitro studies of CNS infection by Cryptococcus neoformans. Eukaryotic Cell. 2009;8:1803-1807.
Eigenheer RA, Lee YJ, Blumwald E, Phinney BS, Gelli A. Extracellular GPI-anchored mannoproteins and proteases of cryptococcus neoformans. FEMS Yeast Res. 2007 Jan.
Liu M, Du P, Heinrich G, Cox GM, Gelli A. Cch1 mediates calcium entry in cryptococcus neoformans and is essential in low-calcium environments. Eukaryot Cell. 2006;5:1788-1796.
George MD, Samarkan S, Reay E, Gelli A, Dandekar S. High-throughput gene expression profiling indicates loss of intestinal growth factors and cell-cycle mediators during primary simian immunodeficiency virus infection. Virol. 2003;312:84-94.