Angela Gelli, Ph.D.
Research/Academic Interests
Virulence determinants of fungal pathogenesis
Synopsis:
Cryptococcus neoformans is a human fungal pathogen that causes an invasive and life-threatening
infection primarily in patients with a compromised immune system. Once cryptococcal cells
disseminate into the bloodstream, they cross the blood-brain barrier (composed of the brain
endothelium) and cause meningoencephalitis, an often-deadly infection. C. neoformans is now the
leading cause of fungal meningitis world-wide and accounts for a significant proportion of AIDSrelated infections. How cryptococcal cells manage to breach the blood-brain barrier and enter the
brain is not fully understood. Through the use of proteomics, molecular biology and an in vitro
model of the blood-brain barrier, we are identifying and examining the role of several key surface
proteins of Cryptococcus in breaching the barrier and promoting brain invasion. Since we believe
that the relationship between cryptococcal cells and the brain endothelium is highly dynamic we
are identifying the temporal protein expression profiles of the brain endothelium in response to C.
neoformans. We anticipate that these studies will lead to an understanding of the mechanisms that
promote the invasion of cryptococcal cells into the CNS, which we can then manipulate and
exploit for the delivery of drugs into the brain to treat brain cancers and neurodegenerative
diseases. In addition, the identification of key proteins (either on the pathogen or the brain
endothelium) that facilitate CNS invasion may lead the way to the development of drugs that
prevent fungal meningitis.
Treating a cryptococcal infection in an immunosuppressed individual is challenging in part because
some of the best antifungal drugs (like azoles) are not fungicidal. We have characterized a calcium
channel (Cch1-Mid1) in the plasma membrane of Cryptococcus neoformans that appears to be a
promising target for the development of small molecules that could be used in combination to
promote fungicidal activity of azoles. We are performing a high-throughput screen to identify
molecules that target the channel and we expect to identify several new molecules that will have
clinical relevance. We have also used a multidisciplinary approach (electrophysiology, molecular
biology and cell biology) to characterize the role of this calcium channel in the pathogen. We
found that cryptococcal cells require this channel when trying to survive in environments that are
low in calcium such as macrophages. We have also performed the first mechanistic study of this
calcium channel and found that it functions as a store-operated calcium selective channel that is
essential for the survival of cryptococcal cells during ER (endoplasmic reticulum) stress. The ability
of the channel to get to the plasma membrane where its function is required is dependent on a
secondary protein, elongation factor 3. This protein has been of interest for a long time because it is
an essential protein and it does not have a human homologue making it the perfect antifungal drug
Angela Gelli, Ph.D.
target. We are currently exploring how and when the two proteins associate and resolving the
molecular mechanism of their interaction.
Lab Page:
Gelli Lab
Title
Associate Professor
Specialty
Pharmacology
Department
Pharmacology
Division
Pharmacology
Address/Phone
Genome and Biomedical Sciences Building, Genome & Biomedical Sciences Facility, 451 Health
Sciences Drive Suite 3503 Davis, CA 95616
Phone: 530-752-3200
Additional Phone
Email
Languages
Education
Phone: 530-754-6446
acgelli@ucdavis.edu
French, Italian
Ph.D., Cell Biology/Electrophysiology, University of Toronto, Ontario, 1997
B.Sc., Chemistry-Biochemistry, University of Toronto, Ontario, 1990
M.Sc., Electrophysiology, University of Toronto, Ontario, 1992
Fellowships
Honors and Awards
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, 1997-2000
Post-Doctoral Scholar, Natural Science and Engineering Research Council of Canada (NSERC),
1997
Select Recent Publications
To view the PubMed publications list for Dr. Gelli, click here
Eigenheer RA, Lee YJ, Blumwald E, Phinney BS, Gelli A. Extracellular GPI-anchored mannoproteins
and proteases of cryptococcus neoformans. (FEMS Yeast Res, published online 19-Jan-2007).
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, 5:1788-1796, 2006.
George MD, Samarkan S, Reay E, Gelli A, Dandekar S. High-throughput gene expression profiling
Angela Gelli, Ph.D.
indicates loss of intestinal growth factors and cell-cycle mediators during primary simian
immunodeficiency virus infection. Virol, 312:84-94, 2003.
Gelli A. Rst1 and Rst2 are required for the a/alpha diploid cell-type in yeast. Mol Microbiol, 46:
845-854, 2002.
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