The overall goal of my research is to identify biomarkers of brain aging in efforts to understand why the aged brain is so vulnerable to neurodegenerative disorders such as Alzheimer's disease. Two general strategies are followed. In a traditional biochemistry approach I am focusing on the age-dependent reduction of an important Ca2+ transporter known as the "plasma membrane Ca2+ -ATPase" (PMCA) in neuronal cell membranes. The protein is essential for proper signaling and information processing in the central nervous system, and the activity of this transporter is markedly decreased in aging brain, a loss that may contribute to a subtle decline in cognitive performance. In studies designed to elucidate potential mechanisms leading to the loss of PMCA, we have found that most of the loss in the protein occurs from specialized plasma membrane micro-domains known as "lipid rafts." Efforts are underway to assess the possibility that lipid composition changes in the rafts or altered trafficking of the PMCA to the rafts underlie the reduction in levels of this important protein in aged brain.
In the second strategy I use proteomics to determine if expression levels of other proteins closely associated with PMCA in the rafts are also reduced with age. Traditional two-dimensional gel electrophoresis (2-DE), coupled with mass spectrometry, was used to identify proteins in synaptic membrane rafts isolated from rat brain. In order to determine differences in protein levels in old vs young raft preparations, we used two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). This technique is designed to improve the quantification of differential expression in comparative proteomics. Our results thus far have revealed an unexpected loss of proteins involved in metabolic homeostasis and protection from oxidative stress, a trend that may contribute to the well-established enhancement of oxidative stress in brain and vulnerability to stress stimuli.
- Post Doctoral Research Associate, 2004-present, Pharmacology & Toxicology, University of Kansas, Kansas, USA
- Ph.D., 2004, Biochemistry & Molecular Biology, Shanghai Jiao Tong University, Shanghai, China and Genomic Technologies Department, F. Hoffmann La Roche Ltd., Basel, Switzerland
- B. S., 1999, Biotechnology, Shanghai Jiao Tong University, Shanghai, China
- Jiang L, Fernandes D, Mehta N, Bean JL, Michaelis ML and Zaidi A (2007). Partitioning of the plasma membrane Ca2+-ATPase into lipid rafts in primary neurons: Effects of cholesterol depletion. J Neurochem. 102(2): 378-88.
- Wan C, La Y, Zhu H, Yang Y, Jiang L, Chen Y, Feng G, Li H, Sang H, Hao X, Zhang G, and He L (2007). Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene. Amino Acids. 32(1): 101-8.
- Wan C, Yang Y, Li H, La Y, Zhu H, Jiang L, Chen Y, Feng G, and He L (2006). Dysregulation of retinoid transporters expression in body fluids of schizophrenia patients. J Proteome Res. 5(11): 3213-6.
- Yang Y, Wan C, Li H, Zhu H, La Y, Xi Z, Chen Y, Jiang L, Feng G, and He L (2006). Altered levels of acute phase proteins in the plasma of patients with schizophrenia. Anal Chem. 78(11): 3571-6.
- Fountoulakis M, Juranville JF, Jiang L, Avila D, Roder D, Jakob P, Berndt P, Evers S, and Langen H (2004). Depletion of the high-abundance plasma proteins. Amino Acids. 27 (3-4): 249-59.
- Jiang L, He L and Fountoulakis M (2004). Comparison of protein precipitation methods for sample preparation prior to proteomic analysis. J Chromatogr A. 1023(2): 317-20.
- Jiang L, Lindpaintner K, Li HF, Gu NF, Langen H, He L and Fountoulakis M (2003). Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia. Amino Acids. 25(1): 49-57.
- Jiang L, Fang J, Nichols DM, Gogichaeva NV, Galeva NA, Michaelis ML, Zaidi A. Age-associated changes in brain lipid raft proteins revealed by two-dimensional fluorescence difference gel electrophoresis. (Manuscript submitted)
- Jiang L, Zaidi A, Bean JL, Michaelis ML. Partitioning of the plasma membrane Ca2+-ATPase into lipid rafts in primary neurons: Effects of GM1 depletion. (Manuscript in preparation)