Ira Blader, PhD
Associate Professor
Ph.D.: 1999, University of Alabama at Birmingham
Pre-OUHSC: Stanford University
Research Interests: Toxoplasma gondii
Teaching: Medical Parasitology, Pathogenic Mechanisms
Email: Ira-Blader@ouhsc.edu
Research Emphasis
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 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.
Second, 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. We are using this model to identify parasite virulence factors and to study immune responses in the eye.
Students who work in my laboratory will have the opportunity to be exposed to many different techniques including microarrays, proteomics, tissue culture, microscopy, biochemistry, RNAi, genetics, and flow cytometry.
Current Laboratory Personnel:
Kevin Brown, Graduate Student
Tiffany Kley, Research Technician
Matt Menedez, Graduate Student
Kazi Rahman, Graduate Student
Crystal Teygong, Research Assistant
Jun Zou, Ph.D., Postdoctoral Fellow
Selected Publications:
"The Host Cell Transcription Factor Hypoxia Inducible Factor 1 is Required for Toxoplasma gondii Growth and Survival at Physiological Oxygen Levels." (2006) W. Spear, D.A. Chan, I. Coppens, R.S. Johnson, A.J. Giaccia, I.J. Blader. Cellular Microbiology, 8:339-352.
"The SAG1 Toxoplasma Surface Protein is Not Required for Acute Ocular Toxoplasmosis in Mice." (2007) E. Charles, M.C. Callegan, I.J. Blader. Infection and Immunity, 75: 2079-2083.
"Toxoplasma gondii Rhoptry Discharge Correlates with Activation of EGR2 Host Cell Transcription." (2008) E. Phelps, K. Sweeney, and I.J. Blader. Infection and Immunity, 76: 4703-4712
"Communication Between Toxoplasma gondii and its Host: Impact on Parasite Growth, Development, Immune Evasion, and Virulence." (2009) I.J.Blader and J.P.Saeij, APMIS 117:458-476.
"The Role of DNA Microarrays in Toxoplasma gondii Research, the Causative Agent of Ocular Toxoplasmosis." (2009) K. M. Brown and I. J. Blader. Journal of Ocular Biology Diseases and Informatics, 2:214-222.
"Host Cell Invasion by Toxoplasma gondii is Temporally Regulated by the Host Microtubule Cytoskeleton." (2010) K. R. Sweeney, S. Lachapelle, N. S. Morrissette, and I.J. Blader. Eukaryotic Cell, 9:1680-9.
"Suppression of CD4 T-Cells by Toxoplasma gondii-Infected Retinal Cells is Mediated by PD-L1." (2010) E. Charles, S. Joshi, J. Ash, B. Fox, D. J. Bzik, M. Lang, and I.J.Blader. Infection and Immunity, 78:3484-3492.
"Toxoplasma gondii Activates Hypoxia-inducible Factor (HIF) by Stabilizing the HIF-1{alpha} Subunit via Type I Activin-like Receptor Kinase Receptor Signaling." (2010) M. Wiley, K.R. Sweeney, D. A. Chan, K. M. Brown, C. McMurtrey, E. W. Howard, A.J. Giaccia, and I.J. Blader. Journal of Biological Chemistry, 285:26852-26860.
"Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells." (2011) M. Wiley, C. Te