Dr. Staudt's laboratory focuses on the molecular cloning and characterization of novel lymphoid-restricted genes that regulate the development and function of lymphocytes. Subtractive hybridization cDNA libraries have been used in conjunction with differential screening of cDNA libraries and automated DNA sequencing to isolate genes that are expressed predominantly in B and/or T lymphocytes. One lymphoid- restricted gene, Ly-GDI, encodes a protein bearing striking homology to a regulator of the ras-like G protein, rho. Ly-GDI inhibits the GTP/GDP exchange of rho and becomes phosphorylated during T cell activation. The cloning of Ly-GDI suggests a mechanism by which signal transduction through the ras-like GTP binding proteins can be regulated in a cell type- specific fashion. Another lymphoid-restricted gene, JAW1, encodes a transmembrane protein which, surprisingly, resides in the endoplasmic reticulum. JAW1 has structural similarity to proteins involved in vesicle transport and fusion suggesting that these processes can be regulated in a lymphoid-restricted fashion. Subtracted cDNA libraries are being generated from normal human lymphocytes or human lymphoid malignancies such as Burkitt's lymphoma and chronic lymphocytic leukemia. Rapid and large scale automated DNA sequencing of such libraries has thus far resulted in the identification of over 30 novel lymphoid-restricted genes. The laboratory is currently characterizing in detail several of these novel genes which are predicted to encode nuclear proteins and which may regulate gene expression in a lymphoid-specific fashion.
