Our goals are to develop novel methods which rapidly identify genes in living cells and lead pharmaceutical compounds in the area of immunomodulation. We will develop a functional read-out for tagged genes that uses a highly sensitive beta-lactamase (bla) gene reporter system to rapidly 1) screen for novel genes responsive to immunomodulatory agents in living cells and 2) identify drug candidates with different specificity from existing drugs. We hypothesis that this gene tagging strategy can be used to create a set of stably transfected T cell lines expressing immunomodulatory genes and to rapidly screen for novel immunosuppressive agents that prevent expression of those genes.
Over $1 billion worth of immunosuppressants are used annually in attempts to prevent graft rejection and graft virsus host reactions. However, immunosuppressant therapy carries serious risk of nephrotoxicity and hypertension, along with substantial related cost for ongoing monitoring of renal function. Thus there is a need for improved immunosuppressive agents or combinations of agents which exhibit more desirable pharmacokinetics.
