Dr. Klysik studies genes involved in tumor suppression and signal transduction. He uses chemical mutagenesis and KO approaches in his work.

Institutions

SS

Research Description

Recessive tumor suppressor genes revealed their widespread involvement in sporadic and familiar cancers. It is now understood that these proteins regulate diverse cellular activities, including cell cycle checkpoint responses, detection and repair of DNA damage, protein ubiquitination and degradation, mitogenic signaling, cell specification, differentiation and migration, and tumor angiogenesis. Studies of these genes have become a centerpiece of contemporary cancer research.

The signal transduction research is a key to understanding the mechanisms by which signaling cascades convert the different external stimuli into specific cellular responses. We are particularly interested in the MAP kinase cascade. It is an evolutionarily conserved cascade that can be activated by a range of signals to stimulate numerous cellular processes including growth and differentiation. The MAP signaling pathway consists of a MAP kinase kinase kinase (MKKK) capable to phosphorylate and activate a MAP kinase kinase. The MAP kinase kinase phosphorylates the activation domain of MAP kinase. The subfamily of MAP kinases, the ERKs, are activated by number of stimuli including growth factors, through a cascade of events in which Ras, Raf-1 kinase, and MEK/ERK kinase (MEK) play a central role. Recently, an inhibitory protein (RKIP) has been identified and found interacting with the kinase domain of Raf-1, to inhibit the MAPK signaling pathway. RKIP can interact with Raf, as well as MEK and ERK. It has also been shown that RKIP could be a potent regulator of NF-_B pathway. We generate KO mice and use them in modeling studies of tumor suppression and signal transduction.

Awards

Not Available

Affiliations

None

Funded Research

P20 RR015578-06, 2005-2010