Ph.D. Biochemistry and Molecular Biology
2004, Louisiana State University Medical Center
Research Focus Areas
Cell and Developmental Biology
Microbial pathogens utilize a variety of strategies to facilitate survival in the infected host. One of the most important mechanisms is the ability to respond to stress and adapt to an adverse host environment. Therefore, inhibiting stress response pathways constitutes a promising antimicrobial therapy.
I study a human fungal pathogen Cryptococcus neoformans to understand the mechanistic cellular processes used by pathogenic microorganisms to allow survival in the infected host. C. neoformans is a major opportunistic fungal pathogen worldwide and a leading cause of morbidity and mortality in AIDS patients. In addition, the sibling species, Cryptococcus gattii is responsible for the recent outbreak of fungal-caused meningitis in the Pacific north-west of the U.S.
Our work with C. neoformans has led us to hypothesize that this pathogen has evolved unique pathways to control cell division in a manner that allows it to survive within a human host. Testing this hypothesis would provide insights into how eukaryotic pathogens adapt to the host environment and could potentially reveal new targets for therapeutic interventions. In addition, our research will lead to an improved understanding of the evolutionary events that have resulted in alternative mechanisms of mitosis. My research program has the following three main aims: 1. Explore molecular basis for stress-induced changes in ploidy in C. neoformans, 2. Explain the intriguing interconnection between cytokinesis, endocytosis, and stress response in C. neoformans, 3. Elucidate the function of septins, filament forming GTPases, in stress response and pathogenicity of C. neoformans.
Figure 1. Scanning Electron Microscope image of an abnormal basidium (specialized spore producing cell) of Cryptococcus neoformans mutant that lacks properly assembled septin filaments.
Figure 2. 3D reconstruction model of Cryptococcus neoformans yeast cell showing centromeres (red) and microtubules (green).
National Institutes of Health; Mechanisms of fluconazole-induced aneuploidy in Cryptococcus neoformans
Introduction to Genetics
Molecular Genetics Lab
Janbon G et al. Analysis of the genome and transcriptome of Cryptococcus neoformans var. grubii reveals complex RNA expression and microevolution leading to virulence attenuation. PLoS Genet. 2014 Apr 17;10(4)
Kozubowski L, Yadav V, Chatterjee G, Sridhar S, Yamaguchi M, Kawamoto S, Bose I, Heitman J, Sanyal K, Ordered kinetochore assembly in the human fungal pathogen basidiomycetous yeast Cryptococcus neoformans, MBio, 2013 Oct 1;4(5)
Ballou ER, Kozubowski L, Nichols CB, Alspaugh JA, Ras1 Acts through Duplicated Cdc42 and Rac Proteins to Regulate Morphogenesis and Pathogenesis in the Human Fungal Pathogen Cryptococcus neoformans., PLoS Genet. 2013 Aug 9 (8)
Kozubowski L, Heitman J, Profiling a killer, the development of Cryptococcus neoformans, FEMS Microbiol Rev., 2012 Jan; 36(1):78-94
Aboobakar EF, Wang X, Heitman J, and Kozubowski L, The C2 domain protein Cts1 functions in the calcineurin signaling circuit during high temperature stress responses in Cryptococcus neoformans, Eukaryot Cell, 2011 Dec; 10(12):1714-23
Kozubowski L, Aboobakar AF, Cardenas ME, Heitman J, Calcineurin co-localizes with P-bodies and stress granules during thermal stress in Cryptococcus neoformans, Eukaryot Cell 2011 Nov; 10(11):1396-402
Kozubowski L, Thompson JW, Cardenas ME, Moseley MA, Heitman J, Association of Calcineurin with the COPI Protein Sec28 and the COPII Protein Sec13 Revealed by Quantitative Proteomics, PLoS One. 2011; 6(10):e25280
Kozubowski L, Heitman J, Septins enforce morphogenetic events during sexual reproduction and contribute to virulence of Cryptococcus neoformans, Mol Microbiol, 2010 Feb 25, 658-75
Kozubowski L, Lee SC, Heitman J, Signaling pathways in the pathogenesis of Cryptococcus, Cell Microbiol, 2009 Mar 19, 11:370-80
Kozubowski L, Saito K, Johnson JM, Howell AS, Zyla TR, Lew DJ, Symmetry-Breaking Polarization Driven by a Cdc42p GEF-PAK Complex, Curr Biol, 2008 Nov 25, 18:1719-26