Research in the Culotta lab focuses on the role of metal ions and oxygen radicals in biology and disease. Metal ions such as copper, iron and manganese are not only trace nutrients but can be quite toxic. One mechanism of toxicity is through generation of free radicals or so-called reactive oxygen species (ROS) that have been implicated in numerous human disorders from neurodegeneration to cancer and aging to infectious disease. As part of our immune response we attack pathogens through metals and ROS, and successful pathogens have evolved clever ways to thwart these assaults by the host. Using a combination of biochemical, cell biology and molecular genetic approaches we are exploring how microbes and the animals the infect use weapons of metals and ROS at the host-pathogen battleground. Our current emphasis is on the Lyme disease bacterium Borrelia burdorferi and the opportunistic fungal pathogen, Candida albicans.
Besold AN, Gilston BA, Radin JN, Ramsoomair C, Culbertson EM, Li CX, Cormack BP, Chazin WJ, Kehl-Fie TE, Culotta VC. The role of calprotectin in withholding zinc and copper from Candida albicans. Infect Immun. 2018 PMID: 29133349.
Rossi DCP, Gleason JE, Sanchez H, Schatzman SS, Culbertson EM, Johnson CJ, McNees CA, Coelho C, Nett JE, Andes DR, Cormack BP, Culotta VC.PLoS Pathog. Candida albicans FRE8 encodes a member of the NADPH oxidase family that produces a burst of ROS during fungal morphogenesis .PLoS Pathog 2017 PMID: 29194441
Peterson RL, Galaleldeen A, Villarreal J, Taylor AB, Cabelli DE, Hart PJ, Culotta VC. The Phylogeny and Active Site Design of Eukaryotic Copper-only Superoxide Dismutases. J Biol Chem. 2016 PMID: 27535222.
Li CX, Gleason JE, Zhang SX, Bruno VM, Cormack BP, Culotta VC. Candida albicans adapts to host copper during infection by swapping metal cofactors for superoxide dismutase. Proc Natl Acad Sci U S A. 2015 PMID: 26351691.
Gleason JE, Galaleldeen A, Peterson RL, Taylor AB, Holloway SP, Waninger-Saroni J, Cormack BP, Cabelli DE, Hart PJ, Culotta VC. Candida albicans SOD5 represents the prototype of an unprecedented class of Cu-only superoxide dismutases required for pathogen defense. Proc Natl Acad Sci U S A. 2014 PMID: 24711423.
Reddi AR, Culotta VC. SOD1 integrates signals from oxygen and glucose to repress respiration. Cell. 2013 PMID: 23332757.