Brendan P. Cormack, PhD

Professional Titles

• Director, Infectious Disease, Translational Science Intersessions

Primary Academic Title

Professor of Molecular Biology and Genetics

Background

Centers and Institutes

Basic Biomedical Sciences, Institute for

Research Interests

Fungal pathogenesis

Lab Website

Brendan Cormack Laboratory

• The Brendan Cormack Laboratory studies fungal pathogenesis, particularly the host-pathogen interaction for the yeast pathogen Candida glabrata. We are trying to identify virulence genes (genes that evolved in response to the host environment) by screening transposon mutants of C. glabrata for mutants that are specifically altered in adherence to epithelial cells, in survival in the presence of macrophages and PMNs. We also screen mutants directly in mice for those unable to colonize or persist in the normal target organs (liver, kidney and spleen). We also focus research on a family of genes--the EPA genes--that allow the organism to bind to host cells. Our research shows that a subset of them are able to mediate adherence to host epithelial cells. We are trying to understand the contribution of this family to virulence in C. glabrata by figuring out what the ligand specificity is of different family members, how genes are normally regulated during infection, and what mechanisms normally act to keep the genes transcriptionally silent and how that silence is regulated.

Research Summary

Dr. Cormack is interested in how microbial pathogens have evolved to colonize and persist in the mammalian host. His lab studies the fungal pathogen Candida glabrata, an opportunistic pathogen responsible for 15 to 20 percent of Candidiasis in the U.S.

Dr. Cormack and his research team focus on two areas of investigation. First, they have generated large numbers of transposon mutants oaf C. glabrata and are screening these for mutants that are specifically altered in adherence to epithelial cells, in survival in the presence of macrophages and PMNs. Second, they are concentrating on a family of genes (the EPA genes) that allow the organism to bind to host cells.

They are trying to understand the contribution of this family to virulence in C. glabrata by addressing three questions, using the genetic tools they have already put in place:

• What is the ligand specificity of different family members?
• How are the genes normally regulated during infection?
• What mechanisms normally act to keep the genes transcriptionally silent and how is that silencing regulated?

Selected Publications

• Castaño I, Pan SJ, Zupancic M, Hennequin C, Dujon B, Cormack BP. "Telomere length control and transcriptional regulation of subtelomeric adhesins in Candida glabrata." Mol Microbiol. 2005 Feb;55(4):1246-58.

• Castano I, Kaur R, Pan S, Cregg R, Penas Ade L, Guo N, Biery MC, Craig NL, Cormack BP. "Tn7-based genome-wide random insertional mutagenesis of Candida glabrata." Genome Res. 2003 May;13(5):905-15. Epub 2003 Apr 14.

• De Las Peñas A, Pan SJ, Castaño I, Alder J, Cregg R, Cormack BP. "Virulence-related surface glycoproteins in the yeast pathogen Candida glabrata are encoded in subtelomeric clusters and subject to RAP1- and SIR-dependent transcriptional silencing." Genes Dev. 2003 Sep 15;17(18):2245-58. Epub 2003 Sep 2.

• Domergue R, Castaño I, De Las Peñas A, Zupancic M, Lockatell V, Hebel JR, Johnson D, Cormack BP. "Nicotinic acid limitation regulates silencing of Candida adhesins during UTI." Science. 2005 May 6;308(5723):866-70. Epub 2005 Mar 17.

• Frieman MB, Cormack BP. "The omega-site sequence of glycosylphosphatidylinositol-anchored proteins in Saccharomyces cerevisiae can determine distribution between the membrane and the cell wall." Mol Microbiol. 2003 Nov;50(3):883-96.

• Frieman MB, McCaffery JM, Cormack BP. "Modular domain structure in the Candida glabrata adhesin Epa1p, a beta1,6 glucan-cross-linked cell wall protein." Mol Microbiol. 2002 Oct;46(2):479-92.

• Kaur R, Ma B, Cormack BP. "A family of glycosylphosphatidylinositol-linked aspartyl proteases is required for virulence of Candida glabrata." Proc Natl Acad Sci U S A. 2007 May 1;104(18):7628-33. Epub 2007 Apr 24.

Courses & Syllabi

Translational Science Intersessions

Honors

• Searle Scholarship Award, 1/1/99
• Burroughs Wellcome Career Award, 1/1/97
• Helen Hay Whitney Postdoctoral Fellowship, 1/1/94
• Howard Hughes Pre-doctoral Fellowship, 1/1/88
• Gold Medal in Science, 1/1/86

Graduate Program Affiliations

• Cellular and Molecular Medicine

Professional Activities

• Cellular Microbiology, Editor, 1/1/00 - 1/1/03
• Comparative and Functional Genomics, Editor, 1/1/00 - 1/1/04
• Johns Hopkins School of Medicine, Institute for Excellence in Education (IEE) Education Awards Selection Committee
• Johns Hopkins School of Medicine, MD-PhD Committee

Additional Training

Stanford University, Stanford, CA, 1997, Pathogenesis of Candida albicans and Candida glabrata