Mechanisms of Cellular Transformation by HTLV-1

National Institute Of Allergy And Infectious Diseases

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Abstract

This project is to understand the processes used by the human T cell leukemia virus type 1 (HTLV-1)for the transformation of human cells. There are several concepts on how a cell can progress from normal physiology to achieve a transformed phenotype. To characterize transformation, we have studied cellular genetic integrity, cell cycle progression and the checkpoints within a cell that guard normal cellular division. We have studied several cellular proteins whose functions are perturbed by the HTLV-1 viral oncoprotein, Tax, during the course of cellular transformation. In the 2009 - 2010 period, we have made the following scientifc findings. 1) We discovered that the Tax oncoprotein can elicit reactive oxygen species (ROS) which leads directly to DNA damage. DNA damage is a common finding in cancers. 2) We have identified small molecules that can inhibit the activity of oncogenic microRNAs, and we showed that these molecules can inhibit tumorigenesis. 3) We have characterized how changes in nuclear envelope proteins alter gene expression profile inside cells.