Research Areas

The Sebti lab research efforts are focused on understanding the mechanisms by which aberrant signal transduction pathways, particularly those mediated by small GTPases such as KRas, contribute to the onset of cancer, and developing novel anticancer drugs based on interfering with these pathways. The lab expertise spans from cancer molecular and cellular biology, computational biology, drug design and discovery to validation in human cancer cells, animal models, and biomarker-driven human clinical trials of novel anticancer drugs.

A major focus is on understanding the mechanism by which the small GTPase KRas causes cancer in the deadliest cancers such as pancreatic cancer. The following are examples of research programs pursued in his laboratory:

1. Unravelling the mechanism by which human tumors become addicted to mutant KRas by integrating cancer cell biology with computational biology.

2. Identifying transcriptome and proteome signatures that predict KRas dependency, patient overall survival and response to therapy.

3. Discovering cell surface proteins that are selectively expressed in mutant KRas addicted human tumors, and understanding their contribution to KRas addiction.

4. Developing drugs that a) bind directly to KRas, b) interfere with binding of KRas to its effectors, c) prevent KRas membrane binding, and d) inhibit kinases and other proteins that are required for mt KRas to cause cancer, with the ultimate goal of thwarting and killing tumors that are addicted to mt KRas.

5. Understanding the mechanism by which KRas regulates the tumor suppressor gene p53.

6. Combining targeted therapy with chemo and immune therapies to treat cancer.