Fuyu Tamanoi, Ph.D. Director	Kathleen Sakamoto, M.D., Ph.D. Co-Associate Director	Carolyn Britten, M.D. Co-Associate Director

Overview:

The Signal Transduction and Therapeutics Program investigates the multiple signaling pathways and related genetic alterations that occur during formation of cancer cells and tumors. Signal transduction pathway studies are carried out by employing phospho-protein analysis, cell cycle, gene expression studies and chemical genetics approaches.

Goals:

• To understand signal transduction events in the development of cancer by identifying new genes involved in cell signaling pathways
• To develop new methods to detect changes in signaling events
• To develop inhibitors of signal transduction that could lead to new anti-cancer therapies

Meetings and Events:

• Quarterly meetings for new members to present their research
• Quarterly seminars given by members of the program area
• Quarterly seminars given by invited speakers from outside institutions
• Twice a year mini-symposia on Signal Transduction and Cancer Therapeutics

Leadership:

Dr. Fuyu Tamanoi, Director of the Signal Transduction and Therapeutics Program Area, has been engaged in the study of the Ras protein for the past twenty years. This protein plays a central role in the growth factor signaling pathway, and has been studied as a model system for the function of small G-proteins. Tamanoi's laboratory studies the mechanisms of Ras membrane association. Tamanoi has also been instrumental in identifying and characterizing inhibitors of farnesyltransferase which are being evaluated in clinical trials. In addition, his lab is involved in the characterization of the TSC/Rheb/mTOR signaling pathway that is critical for growth in response to nutrient and energy conditions.

Co-Associate Director Dr. Kathleen Sakamoto and her colleagues are working to understand the role of a protein known as CREB in leukemias. CREB controls genes that are critical for cell growth and survival. Sakamoto and her associates have found that CREB is overproduced in the leukemia cells from patients with leukemia compared to healthy individuals. They are seeking to understand why CREB is overproduced at the molecular level. Sakamoto is also currently developing a completely different approach to block the effects of hormones, such as estrogen or androgen, which stimulate the growth of cancer cells. Her technology is a molecular bridge or Protac, which uses the cell's own destruction machinery to kill cancer cells. Dr. Sakamoto is also studying new small molecule compounds that inhibit signaling molecules on leukemia cell lines and animal models.