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职业迁徙
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Research Abstract
Lymphocytes circulate through the blood and lymphoid tissues in a resting state. Upon encountering antigens, they become activated to proliferate and differentiate. Lymphocytes also respond to other environmental cues, including cytokines and cell surface proteins on neighboring cells. The transmission of signals from outside the cell to the inside to modulate cell behavior is termed signal transduction.
Activation of phosphoinositide 3-kinase (PI3K) is a critical step in signal transduction pathways triggered by a variety of extracellular stimuli. The lipid products of PI3K serve as second messengers to recruit specific phospholipid-binding proteins to the plasma membrane. Excessive activation of PI3K signaling can cause transformation of certain cell types in vitro and has been observed in many tumors. Many isoforms of PI3K are expressed in mammalian cells, and many putative effector proteins have been identified. One crucial protein kinase downstream of PI3K is the mammalian target of rapamycin (mTOR). My laboratory is interested in the role of PI3K and mTOR in the function of normal cells and in the development of cancer cells. We are particularly interested in cells of the immune system, both normal lymphocytes and their transformed counterparts. Using gene targeting and pharmacological approaches we study the role of PI3K and mTOR in lymphocyte development, activation, and transformation. We are also studying how different mTOR substrates carry out proliferation and survival programs.
A new area of research in the lab involves identifying combination strategies to enhance cancer cell killing by an emerging class of drugs known as BH3 mimetics. These compounds directly bind to BCL2 family members at the mitochondria and promote apoptosis.
Lymphocytes circulate through the blood and lymphoid tissues in a resting state. Upon encountering antigens, they become activated to proliferate and differentiate. Lymphocytes also respond to other environmental cues, including cytokines and cell surface proteins on neighboring cells. The transmission of signals from outside the cell to the inside to modulate cell behavior is termed signal transduction.
Activation of phosphoinositide 3-kinase (PI3K) is a critical step in signal transduction pathways triggered by a variety of extracellular stimuli. The lipid products of PI3K serve as second messengers to recruit specific phospholipid-binding proteins to the plasma membrane. Excessive activation of PI3K signaling can cause transformation of certain cell types in vitro and has been observed in many tumors. Many isoforms of PI3K are expressed in mammalian cells, and many putative effector proteins have been identified. One crucial protein kinase downstream of PI3K is the mammalian target of rapamycin (mTOR). My laboratory is interested in the role of PI3K and mTOR in the function of normal cells and in the development of cancer cells. We are particularly interested in cells of the immune system, both normal lymphocytes and their transformed counterparts. Using gene targeting and pharmacological approaches we study the role of PI3K and mTOR in lymphocyte development, activation, and transformation. We are also studying how different mTOR substrates carry out proliferation and survival programs.
A new area of research in the lab involves identifying combination strategies to enhance cancer cell killing by an emerging class of drugs known as BH3 mimetics. These compounds directly bind to BCL2 family members at the mitochondria and promote apoptosis.
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