Dr. Xin Liu's research seeks to understand the molecular basis of nervous system development, plasticity and neurodegenerative diseases. He and his colleagues are using gene targeting in mice to focus on several important molecules.
The first is a group of molecules called neurotrophins (NTs). NTs are four nerve growth factors that regulate various functions of the nervous system. By generating mutant mouse strains that lack different types of NTs, Liu and his associates concluded that NTs are essential for the survival of peripheral sensory neurons during development and promote neuronal survival after stroke in adult mice. Also, NT-4 plays a physiological role in long-term memory, LTP and morphine tolerance.
The second molecule Liu is studying is the Delta-catenin (d-cat). The d-cat is among the group of catenin molecules. The d-cat interacts with Presenilin1 (PS1) and is expressed exclusively in the brain. Mutations in PS1 can lead to early onset of Alzheimer's disease. The d-cat associates with cadherins and may have an important role in synaptic adherens. Liu and his colleagues have derived mice that lack the expression of d-catenin and found d-cat mutants have a significant deficit in learning and LTP. Recently, they have focused on the molecular mechanisms of d-cat.
The third molecule of study is the PTEN (phosphatase and tensin homolog deleted from chromosome 10). PTEN is a very important regulator. By generating targeted PTEN mutation, Liu has learned that loss of PTEN function results in accumulation of PIP3 and activation of its downstream signaling molecule, Akt/PKB. Recently, he and his colleagues have derived tissue specific PTEN mutant mice and are studying the PTEN's function in the growth, neuronal survival and plasticity of the nervous system.
Li G, Hu Y, Huo Y, Liu M, Freeman D, Gao J, Liu X, Wu DC, Wu H. PTEN deletion leads to up-regulation of a secreted growth factor pleiotrophin. J Biol Chem. 2006 Apr 21;281(16):10663-8. Epub 2006 Feb 28.
Smith DJ, Leil TA, Liu X. Neurotrophin-4 is required for tolerance to morphine in the mouse. Neurosci Lett. 2003 Apr 10;340(2):103-6.
Lesche R, Groszer M, Gao J, Wang Y, Messing A, Sun H, Liu X, Wu H. Cre/loxP-mediated inactivation of the murine Pten tumor suppressor gene. Genesis. 2002 Feb;32(2):148-9.
Li G, Robinson GW, Lesche R, Martinez-Diaz H, Jiang Z, Rozengurt N, Wagner KU, Wu DC, Lane TF, Liu X, Hennighausen L, Wu H. Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development. 2002 Sep;129(17):4159-70.
Stiles B, Gilman V, Khanzenzon N, Lesche R, Li A, Qiao R, Liu X, Wu H. Essential role of AKT-1/protein kinase B alpha in PTEN-controlled tumorigenesis. Mol Cell Biol. 2002 Jun;22(11):3842-51.