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Fang Liu
fangl_aaaat_pharmacy_dot_purdue_dot_edu
PhD Candidate
Dept of MCMP, Purdue University
575 Stadium Mall Drive, 512
West Lafayette, IN 47907 |
I am pursuing my Ph.D. degree in Purdue
University since Fall 2004. My advisor is Dr.
Jean-Christophe Rochet, and I am a member of
the Rochet Lab at Purdue. Before coming to Purdue, I got my
bachelor degree from Fudan University
in 2004.
Research
Parkinson's disease is a neurodegenerative disorder characterized by difficulty
initiating movement, resting tremor and rigidity. These symptoms are primarily
the result of a loss of dopaminergic neurons in the substantia nigra.
Preliminary studies in our lab suggest that in primary mesencephalic cultures,
overproduction of human A53T a-synuclein via lentivirus-mediated gene delivery
selectively kills dopaminergic neurons. Also, exposure of primary neurons to the
mitochondrial complex I inhibitor, rotenone, induces dopaminergic cell death. In
addition, proteasome dysfunction induced by proteasome inhibitors such as MG 132
and lactacystin leads to the selective death of dopaminergic neurons.
My research is focusing on using the primary mixed midbrain cultures to screen
small molecules that protect primary neurons against toxic effects.
Pharmacological treatment and immunocytochemistry are performed to examine the
viability of dopaminergic neurons under different conditions. The goal of these
studies is to explore the protective effects of various antioxidant compounds.
I am also using the primary cell-culture model to investigate the effect of
antioxidant proteins such as methionine sulfoxide reductase A (MsrA) and DJ-1 on
the selective death of dopaminergic neurons. To determine whether the
suppression of these proteins causes selective dopaminergic cell death, I am
examining the effects of silencing the gene encoding rat DJ-1 or MsrA by RNAi. A
long-term goal is to investigate the molecular pathways upstream or downstream
of DJ-1, MsrA, and a-synuclein to better understand the mechanism of protective
or toxic effects of these important Parkinson's disease-related proteins.
These studies will enable us to achieve a better understanding of the
pathogenesis of Parkinson disease, and the midbrain mixed cell culture is also a
powerful tool for the discovery of new drug candidates.
Publications
- Cooper A.A., Gitler A.D., Cashikar A., Haynes C.M., Hill K.J.,
Bhullar B., Liu K., Xu K., Strathearn K.E., Liu F., Cao S.,
Caldwell K.A., Caldwell G.A., Kolodner R.D., LaBaer J., Rochet J.-C.,
Bonini N.M. & Lindquist, S. (2006) Alpha-Synuclein Blocks ER-Golgi Traffic and
Rab1 Rescues Neuron Loss in Parkinson's Models. Science , 313, 324-
328. (PubMed)
-
Outeiro T.F., Klucken J., Strathearn K.E., Liu F., Nguyen P., Rochet J.-C., Hyman B.T., McLean P.J.,
Small heat shock proteins protect against alpha-synuclein-induced toxicity and aggregation.
Biochem Biophys Res Commun. 2006 Dec 22;351(3):631-8. Epub 2006 Oct 26.
(PubMed)
- Liu F., Nguyen J.L., Hulleman J.D., Li L., Rochet J.-C.,
Mechanisms of DJ-1 neuroprotection in a cellular model of Parkinson's disease.
J Neurochem. 2008 Apr 15. (PubMed)
-
Liu F., Nguyen J.L., Hindupur J., Ruf K.J., Zhu J., Schieler J.L., Bonham C.C., Wood K.V., Davisson V.J., and Rochet J.-C.,
Methionine sulfoxide reductase A protects dopaminergic cells from Parkinson's disease-related insults.
Free Radical Biology and Medicine. March 2008.
Awards
- Purdue research foundation award, 2007-2008
- Jekins-Knevel Award for Outstanding Graduate Research, October 2008
- Ronald W. Dollens Graduate Scholarship in the Life Sciences, October 2008
Last
updated: Tuesday November 18, 2008