Ira Blader PhD
SUNY Buffalo, Microbiology and Immunology
Current Position: Associate Professor
Keywords Research Areas: Chorioretinitis; Inflammation, Infections, Parasitology; Hypoxia
- Ocular Infection, Inflammation, and Immunology
Synopsis Of Research:
Toxoplasma gondii is an obligate intracellular parasite that has the unique ability of infecting most nucleated cells in almost all warm-blooded animals. It is one of the most widespread infections throughout the world with ~ 50% of the world's population infected. Luckily, most infected people are asymptomatic but in AIDS patients and other immune-compromised individuals, Toxoplasma causes serious and life-threatening disease. Besides its own medical importance, we study Toxoplasma because it represents an ideal model system to study how other related pathogens cause disease. These include Plasmodium, which is the causative agent of malaria that is responsible for millions of death worldwide, and Cryptosporidium, which causes another important secondary infection in AIDS patients. The reason why Toxoplasma is a great model system is that it can easily be grown in vitro, its genome has been sequenced, and it can be genetically manipulated.
Our research is focused on two different but related questions. First, we want to know how Toxoplasma causes ocular disease. This is an important question because even though millions of people throughout the world suffer from ocular toxoplasmosis, we know almost nothing about either how the parasite grows in the eye or how the immune system in the eye is activated to fight the infection. To address this question, we have developed a murine ocular toxoplasmosis model. Using this model, we have demonstrated that immunosuppressive molecules are required to prevent immune-mediated pathology following infection and that the parasite expresses retinal specific virulence factors.
Second, we want to know how the parasite grows inside of its host cell. One of the important things Toxoplasmamust do to grow is hijack pathways in its host cell. We are using functional genomic assays such as microarrays and genome-wide RNAi screens to identify these pathways. Identifying these pathways is important because if the parasite cannot use these pathways, the parasite will not grow or cause disease. Thus, these pathways represent novel drug targets. As an example, we have discovered that oxygen-regulated transcription factors in the host cell are necessary to support parasite growth. We are currently identifying how these transcription factors function and how the parasite adapts to the various oxygen environments it encounters during its lifecycle.
Current Or Representative Publications:
- Regulation of immunopathogenesis during Plasmodium and Toxoplasma infections: more parallels than distinctions? Butler NS, Harris TH, Blader IJ. Trends Parasitol. 2013 Dec;29(12):593-602.
- The Skp1 protein from Toxoplasma is modified by a cytoplasmic prolyl 4-hydroxylase associated with oxygen sensing in the social amoeba Dictyostelium. Xu Y, Brown KM, Wang ZA, van der Wel H, Teygong C, Zhang D, Blader IJ, West CM. J Biol Chem. 2012 Jul 20;287(30):25098-110.
- Serum response factor regulates immediate early host gene expression in Toxoplasma gondii-infected host cells.
Wiley M, Teygong C, Phelps E, Radke J, Blader IJ. PLoS One. 2011 Mar 29;6(3):e18335.
- Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF-1alpha subunit via type I activin-like receptor kinase receptor signaling. Wiley M, Sweeney KR, Chan DA, Brown KM, McMurtrey C, Howard EW, Giaccia AJ, Blader IJ. J Biol Chem. 2010 Aug 27;285(35):26852-60.
- CD4 T-cell suppression by cells from Toxoplasma gondii-infected retinas is mediated by surface protein PD-L1.
Charles E, Joshi S, Ash JD, Fox BA, Farris AD, Bzik DJ, Lang ML, Blader IJ. Infect Immun. 2010 Aug;78(8):3484-92.