My research has focused on understanding how the immune system develops and how abnormalities in its development can lead to disease. We have identified a gene that regulates the development and proper function of the immune system. Defects in this gene, named Ikaros, can lead to a range of immune system diseases including immunodeficiencies and T-cell leukemias in a mouse model system. We have shown that Ikaros can function as a regulator of transcription, suggesting that its role is to regulate gene expression in immune system cells. Ikaros is an essential gene for the proper development of T-cells. T-cells develop in the thymus where they learn to differentiate between proteins which make up the body or self, and those which comprise invaders. The T-cells which are allowed to develop are those which can mount the most effective immune responses against foreign antigens without causing autoimmunity. However, in mice which cannot express the Ikaros protein due to a gene mutation, defective T-cells are allowed to develop resulting in a faulty immune system.
The genetic basis for this aberrant T-cell differentiation in the absence of Ikaros has not yet been discovered. My laboratory is searching for genes whose expression is regulated by Ikaros in order to define not only the molecular role of Ikaros in T-cell development , but also the programs of gene expression which must be induced for a precursor to develop into a mature, functional T-cell.
Publications:
Winandy, S., L. Wu, J.-H. Wang and K. Georgopoulos. (1999) Pre-TCR and TCR controlled checkpoints in T-cell differentiation are set by Ikaros. The Journal of Experimental Medicine. 190:1039-1048.
Winandy, S., N. Avitahl, C. Freidrich, Y. Ge and K. Georgopoulos. (1999) Ikaros sets thresholds for T-cell activation and regulates chromosome propagation. Immunity 10(3): 333-343..
Avitahl, N., A. Nichogiannopoulou, K. Georgopoulos and S. Winandy. (1998) The Ikaros Gene Family in Hemopoietic Differentiation. Molecular Biology of B and T Cell Development.
