– Cancer cell signaling: Akt/mTOR and Ras/Raf/ERK signaling networks In order for cells to survive environmental stresses and maintain homeostatic balance, a complex cellular signaling network integrates information about the external and internal environment in order to allow for the cells to adapt. In cancer, dysregulation of signaling disrupts the normal and well-controlled physiological homeostasis. Altered signal transduction often provides cancer cells with advantages during periods of environmental stress and enables them to grow and metastasize. Our research interest is to biochemically and molecularly decode cancer cell signaling, especially PI3K/Akt/mTOR and Ras/Raf/ERK signaling networks that are used by cancer cells to support environmental stress resistance and cancer progression. Students will determine the functions and regulatory mechanisms of these signaling networks, which we believe provide a basis for novel anti-cancer therapeutics.
– Anti-cancer drug resistance mechanism and overcoming strategies: FDA-approved targeted cancer therapy drugs are used in clinics successfully, but one of the major problems of this therapy is cancer’s resistance to the drugs. They initially lead to a dramatic decrease in tumor burden and an increase in overall patient survival. However, tumors in many patients eventually become resistant to these drugs, and tumor recurrence occurs. Thus, it is of utmost importance to determine why some cancers are resistant to targeted cancer drugs and how the resistance can be overcome for successful treatment. Drugs that target mTOR and Raf/MEK signaling networks are used in clinics to treat cancer patients. Students will be involved in identifying cancer’s resistance mechanisms toward mTOR and Raf/MEK targeting drugs and identify strategies to overcome this resistance and prevent tumor recurrence. Our discoveries will provide better approaches and strategies to determine who will benefit from or who should avoid mTOR or Raf/MEK targeting therapy and to design effective synergistic combination therapies to overcome drug resistance.
– Regulation of mRNA translation and metabolism in cancer: With mTOR and Raf/MEK/ERK signaling networks, one of our primary focuses is on the regulation of mRNA translation, a cellular metabolic process that produces proteins. Proteins are essential parts of organisms that participate in virtually every cellular process, including the structural/mechanical maintenance of cells, metabolism, immune response, muscle maintenance, and cell growth. Therefore, mRNA translation is one of the most critical processes in all living organisms, and it is tightly controlled by growth factors, hormones, and diet. The main characteristic of cancer is uncontrolled growth and cell division, which means cancer cells require high amounts of protein production. To meet this requirement, cancer cells develop hyperactive protein synthesis systems. Therefore, targeting dysregulated protein synthesis in cancer is regarded as one of the promising strategies in targeted cancer therapeutics. Students will focus on the mechanisms of dysregulated mRNA translation and metabolism in cancer and determine the therapeutic strategies to regulate them effectively.