Brendan Cormack

Academic Titles: 
Professor
Appointments/Affiliations: 

Biochemistry, Cellular & Molecular Biology (BCMB)
Cellular and Molecular Medicine (CMM)

410-614-4923
Research Interest: 
Fungal pathogenesis: the host-pathogen interaction for the yeast pathogen Candida glabrata

The Cormack lab is focused on the molecular understanding of Candida pathogenesis and virulence. We are finding new pathways involved in the relationship between Candida glabrata and the host, and are defining the evolutionary adaptations of Candida that permit it to so successfully colonize humans and cause disease in susceptible patients. It is hoped that a better understanding of these pathways can be exploited to develop potential antifungal therapies for Candida infections.

 

We have made exciting discoveries about the unusual transcriptional regulation of the EPA loci. All EPA genes are located adjacent to telomeres. Their transcription is subject to epigenetic silencing mediated by members of the Sir2 family of histone deacetylases. We have shown this regulation is important for virulence and that mutants that disrupt the sub-telomeric silencing are less virulent. In characterizing the regulation of the EPA genes, we have analyzed expression of EPA genes during infection and found that some of the transcriptionally silent EPA genes are induced in the host during infection. This occurs as a direct result of limitation for the vitamin niacin (the precursor of NAD+), in the host environment. Since C. glabrata is a niacin auxotroph, limitation results in a drop in intracellular NAD+. Sir2, the histone deacetylase responsible for sub-telomeric silencing, requires NAD+. Therefore, under niacin depleted conditions, Sir2 becomes inactive and the EPA loci are no longer silenced. The linking of vitamin availability to virulence gene expression may be exploited as a mechanism to block Candida virulence and is currently pursued in the lab.

Biosketch: 
Lab Members:
Name Classificationsort descending Email
Cynthia Rogers MBG Administrative Staff crogers4@jhmi.edu
Shih-Jung Pan Postdoctoral Fellow
Selected Publications:
Zordan RE, Beliveau BJ, Trow JA, Craig NL, Cormack BP. (2015) Avoiding the ends: internal epitope tagging of proteins using transposon Tn7. Genetics 200(1):47-58. [ pdf ]
Li CX, Gleason JE, Zhang SX, Bruno VM, Cormack BP, Culotta VC. (2015) Candida albicans adapts to host copper during infection by swapping metal cofactors for superoxide dismutase. Proceedings of the National Academy of Sciences USA 112:38, E5336-E5342. [ pdf ]
Kaur R, Ma B, Cormack BP. (2007). A family of glycosylphosphatidylinositol-linked asparyl proteases is required for virulence of Candida glabrata. Proceedings of the National Academy of Sciences USA. 104:7628-7633. [ link ]
Castaño I, Pan S, Zupancic M, Hennequin C, Dujon B, Cormack BP. (2005). Telomere length control and transcriptional regulation of sub-telomeric adhesins in Candida glabrata. Molecular Microbiology. 55: 1246-1258. [ link ]
Domergue R, Castaño I, De Las Peñas A, Zupancic M, Lockatell V, Hebel JR, Johnson D, Cormack BP. (2005). Nicotinic acid limitation regulates silencing of Candida adhesins during UTI. Science. 308: 866-870 [ link ]
Frieman MB, Cormack BP. (2003). The omega-site sequence of glycosylphosphatidylinositol-anchored proteins in Saccharomyces cerevisiae can determine distribution between the membrane and the cell wall. Molecular Microbiology. 50: 883-896. [ link ]