Recent advances in genome sequencing have provided novel opportunities for biomedical research. Functional genomics is the next logical step to translate the vast nucleic acid sequences into the understanding of biological phenomena. Bioinformatics and proteomics are becoming essential components of functional genomics. Advances in mass spectrometry and other proteomics techniques have provided unprecedented opportunities for the analysis of proteins, such as peptide internal sequencing, post-translation modification, noncovalent interaction, and protein folding.

The identification and quantification of the proteins from complex mixtures within biological context have always been the focus of CAPR. 2-D DIGE, iTRAQ and various high-throughput technologies has been successfully implemented in CAPR for quantifing the protein changes at the proteome level.

One of the goals of our center is to develop and optimize mass spectrometry technologies to study the role of protein post-translational modifications and protein-protein interactions in cell function. Protein phosphorylation, acetylation and oxidative modifications are the initial targets. After the development and optimization of a robust mass spectrometry-based method, we will characterize protein modifications and interactions in the context of disease development and regulation.

Another goal is to discover changes in neuropeptide hormones under oxidative stress in the central nervous system. This will be accomplished via bioinformatics and proteomics approaches. The identified putative neuropeptides will be tested for biological activity using cell-based functional assays. The metabolisms of those neuropeptides will be investigated in order to discover new protease inhibitors that will enhance the function of the hormones.

Recently, CAPR has started metabolomics research using Nuclear Magnetic Resonance spectroscopy (NMR). Metabolomics is the study of the changes in the metabolite levels, which are in dynamic flux in response to drugs, environmental factors and diseases. The low molecular weight metabolites in cells, tissues and biological fluids like urine, plasma and saliva can be analyzed. The method can be applied to both in vitro and in vivo studies. It enables us to rapidly characterize a broad spectrum of small molecules in an organism. Metabolomics is inherently linked to proteomics and genomics. The information collected from metabolomics combined with proteomics provides a more complete picture of what is really happening in a biological system. Metabolite analysis can be rapidly achieved by NMR. The common nuclei observed are proton, carbon, and phosphorous. NMR spectroscopy gives a snapshot of the metabolite levels which can be used to understand the physiology of an organism.

Recent Publications

• Ago, T., Liu, T., Zhai, P., Chen, W., Li, H., Molkentin, J. D., Vatner, S. F., Sadoshima, J., A Redox-Dependent Pathway for Regulating Class II HDACs and Cardiac Hypertrophy . Cell 2008, 133 , 978-993.
• Fu, C., Hu, J., Ago, T., Sadoshima, J., Li, H., Quantitative analysis of redox-sensitive proteome with DIGE and ICAT . J Proteome Res 2008, In press.
• Guan, D., Altan-Bonnet, N., Parrott, A. M., Arrigo, C. J., Li, Q., Khaleduzzaman, M., Li, H., Lee, C.-G., Pe'ery, T., Mathews, M. B., Nuclear factor 45 (NF45) is a regulatory subunit of complexes with NF90/110 involved in mitotic control . Mol Cell Biol 2008, 28 , 4629-4641.
• Jain, M. R., Ge, W. W., Elkabes, S., Li, H., Amyotrophic lateral sclerosis: Protein chaperone dysfunction revealed by proteomic studies of animal models . Proteomics - Clinical Applications 2008, 2 , 670-684.
• Jain, M. R., Liu, T., Hu, J., Darfler, M., Fitzhugh, V., Rinaggio, J., Li, H., Quantitative Proteomic Analysis of Formalin Fixed Paraffin Embedded Oral HPV Lesions from HIV Patients . The Open Proteomics Journal 2008, 1 , 40-45.
• Liu, T., Hu, J., Li, H., Neuroproteomics , Humana Press, Totowa 2008, p. In press.
• Wang, J., Leone, P., Wu, G., Francis, J. S., Li, H., Jain, M. R., Serikawa, T., Ledeen, R., Myelin Lipid Abnormalities in the Aspartoacylase-Deficient Tremor Rat . Neurochemical Research 2008, In press.
• Yan, W., Liu, T., Wu, C., Li, H., A strategy for direct identification of protein nitrosylation sites by a quadrupole time-of-flight mass spectrometer . J Am Soc Mass Spectrom 2008, In press.
• Elkabes, S., Li, H., Proteomic strategies in multiple sclerosis and its animal models . Proteomics - Clinical Applications 2007, 1 , 1393-1405.
• Grant, J. E., Hu, J., Liu, T., Jain, M. R., Elkabes, S., Li, H., Post-translational modifications in the rat lumbar spinal cord in experimental autoimmune encephalomyelitis . J Proteome Res 2007, 6 , 2786-2791.
• Kurnellas, M. P., Lee, A. K., Li, H., Deng, L., Ehrlich, D. J., Elkabes, S., Molecular alterations in the cerebellum of the plasma membrane calcium ATPase 2 (PMCA2)-null mouse indicate abnormalities in Purkinje neurons . Mol Cell Neurosci 2007, 34 , 178-188.
• Liu, T., Donahue, K. C., Hu, J., Kurnellas, M. P., Grant, J. E., Li, H., Elkabes, S., Identification of differentially expressed proteins in experimental autoimmune encephalomyelitis (EAE) by proteomic analysis of the spinal cord . J Proteome Res 2007, 6 , 2565-2575.
• Sayed, N., Baskaran, P., Ma, X., van den Akker, F., Beuve, A., Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation . Proc Natl Acad Sci U S A 2007, 104 , 12312-12317.
• Tibrewal, N., Liu, T., Li, H., Birge, R. B., Characterization of the biochemical and biophysical properties of the phosphatidylserine receptor (PS-R) gene product . Mol Cell Biochem 2007, 304 , 119-125.
• Wang, J., Matalon, R., Bhatia, G., Wu, G., Li, H., Liu, T., Lu, Z. H., Ledeen, R. W., Bimodal occurrence of aspartoacylase in myelin and cytosol of brain . J Neurochem 2007, 101 , 448-457.
• Das, A., Li, H., Liu, T., Bellofatto, V., Biochemical characterization of Trypanosoma brucei RNA polymerase II . Mol Biochem Parasitol 2006, 150 , 201-210.
• Hu, J., Qian, J., Borisov, O., Pan, S., Li, Y., Liu, T., Deng, L., Wannemacher, K., Kurnellas, M., Patterson, C., Elkabes, S., Li, H., Optimized proteomic analysis of a mouse model of cerebellar dysfunction using amine-specific isobaric tags . Proteomics 2006, 6 , 4321-4334.
• Liu, T., D'Mello, V., Deng, L., Hu, J., Ricardo, M., Pan, S., Lu, X., Wadsworth, S., Siekierka, J., Birge, R., Li, H., A multiplexed proteomics approach to differentiate neurite outgrowth patterns . J Neurosci Methods 2006, 158 , 22-29.
• Sleat, D. E., Wang, Y., Sohar, I., Lackland, H., Li, Y., Li, H., Zheng, H., Lobel, P., Identification and validation of mannose 6-phosphate glycoproteins in human plasma reveal a wide range of lysosomal and non-lysosomal proteins . Mol Cell Proteomics 2006, 5 , 1942-1956.
• Christoffers, K. H., Li, H., Howells, R. D., Purification and mass spectrometric analysis of the delta opioid receptor . Brain Res Mol Brain Res 2005, 136 , 54-64.
• Ondrovicova, G., Liu, T., Singh, K., Tian, B., Li, H., Gakh, O., Perecko, D., Janata, J., Granot, Z., Orly, J., Kutejova, E., Suzuki, C. K., Cleavage site selection within a folded substrate by the ATP-dependent lon protease . J Biol Chem 2005, 280 , 25103-25110.
• Reichman, C., Singh, K., Liu, Y., Singh, S., Li, H., Fajardo, J. E., Fiser, A., Birge, R. B., Transactivation of Abl by the Crk II adapter protein requires a PNAY sequence in the Crk C-terminal SH3 domain . Oncogene 2005, 24 , 8187-8199.
• Sleat, D. E., Lackland, H., Wang, Y., Sohar, I., Xiao, G., Li, H., Lobel, P., The human brain mannose 6-phosphate glycoproteome: a complex mixture composed of multiple isoforms of many soluble lysosomal proteins . Proteomics 2005, 5 , 1520-1532.
• Dvorzhinski, D., Thalasila, A., Thomas, P. E., Nelson, D., Li, H., White, E., Dipaola, R. S., A novel proteomic coculture model of prostate cancer cell growth . Proteomics 2004, 4 , 3268-3275.
• Lee, C. G., Hague, L. K., Li, H., Donnelly, R., Identification of toposome, a novel multisubunit complex containing topoisomerase II alpha . Cell Cycle 2004, 3 , 638-647.
• Liu, Y., Porta, A., Peng, X., Gengaro, K., Cunningham, E. B., Li, H., Dominguez, L. A., Bellido, T., Christakos, S., Prevention of glucocorticoid-induced apoptosis in osteocytes and osteoblasts by calbindin-D28k . J Bone Miner Res 2004, 19 , 479-490.
• Wu, K., Bottazzi, M. E., de la Fuente, C., Deng, L., Gitlin, S. D., Maddukuri, A., Dadgar, S., Li, H., Vertes, A., Pumfery, A., Kashanchi, F., Protein profile of tax-associated complexes . J Biol Chem 2004, 279 , 495-508.
• Yan, L., Ge, H., Li, H., Lieber, S. C., Natividad, F., Resuello, R. R., Kim, S. J., Akeju, S., Sun, A., Loo, K., Peppas, A. P., Rossi, F., Lewandowski, E. D., Thomas, A. P., Vatner, S. F., Vatner, D. E., Gender-specific proteomic alterations in glycolytic and mitochondrial pathways in aging monkey hearts . J Mol Cell Cardiol 2004, 37 , 921-929.
• Christoffers, K. H., Li, H., Keenan, S. M., Howells, R. D., Purification and mass spectrometric analysis of the mu opioid receptor . Brain Res Mol Brain Res 2003, 118 , 119-131.
• de la Fuente, C., Wang, L., Wang, D., Deng, L., Wu, K., Li, H., Stein, L. D., Denny, T., Coffman, F., Kehn, K., Baylor, S., Maddukuri, A., Pumfery, A., Kashanchi, F., Paradoxical effects of a stress signal on pro- and anti-apoptotic machinery in HTLV-1 Tax expressing cells . Mol Cell Biochem 2003, 245 , 99-113.
• Peinado, J. R., Li, H., Johanning, K., Lindberg, I., Cleavage of recombinant proenkephalin and blockade mutants by prohormone convertases 1 and 2: an in vitro specificity study . J Neurochem 2003, 87 , 868-878.
• Reichman, T. W., Parrott, A. M., Fierro-Monti, I., Caron, D. J., Kao, P. N., Lee, C. G., Li, H., Mathews, M. B., Selective regulation of gene expression by nuclear factor 110, a member of the NF90 family of double-stranded RNA-binding proteins . J Mol Biol 2003, 332 , 85-98.
• Wang-Su, S. T., McCormack, A. L., Yang, S., Hosler, M. R., Mixon, A., Riviere, M. A., Wilmarth, P. A., Andley, U. P., Garland, D., Li, H., David, L. L., Wagner, B. J., Proteome analysis of lens epithelia, fibers, and the HLE B-3 cell line . Invest Ophthalmol Vis Sci 2003, 44 , 4829-4836.
• Wei, W., Li, H., Nemeria, N., Jordan, F., Expression and purification of the dihydrolipoamide acetyltransferase and dihydrolipoamide dehydrogenase subunits of the Escherichia coli pyruvate dehydrogenase multienzyme complex: a mass spectrometric assay for reductive acetylation of dihydrolipoamide acetyltransferase . Protein Expr Purif 2003, 28 , 140-150.
• Furia, B., Deng, L., Wu, K., Baylor, S., Kehn, K., Li, H., Donnelly, R., Coleman, T., Kashanchi, F., Enhancement of nuclear factor-kappa B acetylation by coactivator p300 and HIV-1 Tat proteins . J Biol Chem 2002, 277 , 4973-4980.
• Che, F. Y., Yan, L., Li, H., Mzhavia, N., Devi, L. A., Fricker, L. D., Identification of peptides from brain and pituitary of Cpe(fat)/Cpe(fat) mice . Proc Natl Acad Sci U S A 2001, 98 , 9971-9976.
• Deng, L., Wang, D., de la Fuente, C., Wang, L., Li, H., Lee, C. G., Donnelly, R., Wade, J. D., Lambert, P., Kashanchi, F., Enhancement of the p300 HAT activity by HIV-1 Tat on chromatin DNA . Virology 2001, 289 , 312-326.
• Li, H., Young, B. J., Wang, H., Schooley, D. A., The structure of ubiquinones isolated from developing embryos of Manduca sexta . Insect Biochem Mol Biol 1998, 28 , 69-73.
• Li, H., Wang, H., Schegg, K. M., Schooley, D. A., Metabolism of an insect diuretic hormone by Malpighian tubules studied by liquid chromatography coupled with electrospray ionization mass spectrometry . Proc Natl Acad Sci U S A 1997, 94 , 13463-13468.
• Li, H., Houle, W., Hackett, M., Schooley, D. A., The Structure of Dolichols Isolated from Manduca sexta Larvae . Insect Biochem Mol Biol 1995, 25 , 1019-1026.