Prof. Karni's lab is interested in how the process of alternative RNA splicing (a fundamental step of gene expression) is de-regulated in human diseases, specially cancer and how the proteins that control this process (splicing factors) contribute to cancer development, tumor progression and the metastatic process. The Karni lab uses various in vitro and in vivo cellular and animal systems as well as molecular technologies to identify the role of splicing factors in human diseases. A major effort in the lab is to translate the molecular findings into therapy. For this, our lab modulates the splicing process by different methods: Splice switching oligonucleotides that change the splicing of specific oncogenes and tumor suppressors as well as specific splicing factor inhibitors developed in the lab called “decoy oligonucleotides”. Additional projects in the lab is to develop new therapies for genetic diseases caused by nonsense mutations such as Duchenne muscular dystrophy (DMD) which causes muscle degeneration and eventually death in affected children. Several of these applications have been commercialized by the technology transfer company of the Hebrew University, Yissum.

Pathways for transformation by SRSF1.

Splicing factor oncoprotein SRSF1 is a transcriptional target of the c-myc proto-oncogene, and can be phosphorylated by SRPK or CLK downstream to Akt. SRSF1 alters the splicing of BIM, BIN1, S6K1 and Mnk2 regulating the mTOR and MAPK pathways, increasing translation and inhibiting apoptosis.