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Proteomics
and Bioinformatics Research
CAPR is located in the University Hospital Cancer Center Building. We have recently acquired a Thermo Electron LTQ Orbitrap Velos with ETD capability. In addition, we are equipped with an Applied Biosytems 4800 Plus MALDI TOF/TOF Analyzer. With these state of the art instruments we are able to perform quantitative proteomics experiments using iTRAQ and ICAT approaches.
Recent advances in genome sequencing have provided unprecedented opportunities for biomedical research. Bioinformatics and proteomics are becoming essential components of systems biology research. Advanced mass spectrometry and other proteomics techniques have provided opportunities for both the qualitative and quantitative analyses of proteins, such as peptide internal sequencing, post-translation modification, non-covalent interaction and protein folding.
The identification and quantification of proteins from complex biological mixtures has remained a focus of CAPR. To this end, 2-D DIGE, iTRAQ and SILAC quantitative proteomics of proteins and their PTMs has been successfully implemented in CAPR for quantifying protein changes at both cell and tissue levels.
One of the goals of CAPR 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, methylation, nitrosylation 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. Please contact Dr. Hong Li to discuss your potential proteomics projects.
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Recent
Publications
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Wu, C., Parrott, A. M., Liu, T., Jain, M. R., Yang, Y., Sadoshima, J. & Li, H. Distinction of thioredoxin transnitrosylation and denitrosylation target proteins by the ICAT quantitative approach. J Proteomics. 2011, in press (Compressed Raw Data)
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Wu, C., Parrott, A. M., Fu, C., Liu, T., Marino, S. M., Gladyshev, V. N., Jain, M. R., Baykal, A. T., Li, Q., Oka, S., Sadoshima, J., Beuve A., Simmons, W. J. & Li, H. Thioredoxin-mediated post-translational modifications: Reduction, transnitrosylation, denitrosylation and related proteomics methodologies. Antioxid Redox Signal. 2011 ,in press.
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Jain, M. R., Li, M., Chen, W., Liu, T., de Toledo, S. M., Pandey, B. N., Li, H., Rabin, B. M. & Azzam, E. I. In vivo space radiation-induced non-targeted responses: late effects on molecular signaling in mitochondria. Curr Mol Pharmacol. 2011, 4, 106-14.
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Cagas, S. E., Jain, M. R., Li, H., Perlin, D. S., Profiling the Aspergillus fumigatus proteome in response to caspofungin. Antimicrob Agents Chemother 2011, 1, 146-154
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Sugino, I. K., Gullapalli, V. K., Sun, Q.,Wang, J., Nunes, C. F.,Cheewatrakoolpong, N.,Johnson, A. C., Degner, B. C., Hua, J., Liu, T., Chen, W., Li, H., & Zarbin, M. A. Cell-Deposited Matrix Improves Retinal Pigment Epithelium Survival on Aged Submacular Human Bruch’s Membrane.Invest Ophthalmol Vis Sci. 2011, 52, 345-58
- Jain, M. R., Liu, T., Wood, T. L., Li, H., in: Karamanos, Y. (Ed.), Expression profiling in neuroscience 2011, p. in press.
- Tyler, W. A., Jain, M. R., Cifelli, S. E., Li, Q., Li, H., Wood, T. L., Proteomic analysis and identification of novel targets regulated by the mTOR pathway during oligodendrocyte differentiation. Glia 2011, in press
- Jain, M. R., Li, Q., Liu, T., Parrott, A. M., Wu, C., Chen, W., Elkabes S. & Li, H. Correlation between immunoproteosome components and experimental autoimmune encephalomyelitis pathology as elucidated by iTRAQ quantitative proteomics. In preparation
2010
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Wu, C., Liu, T., Chen, W., Oka, S., Fu, C., Jain, M. R., Parrott, A. M., Baykal, A. T., Sadoshima, J., Li, H., Redox regulatory mechanism of transnitrosylation by thioredoxin. Mol Cell Proteomics 2010, 9, 2262-2275
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Kurnellas, M. P., Li, H., Jain, M. R., Giraud, S. N., Nicot, A. B., Ratnayake, A., Heary, R. F., Elkabes, S., Reduced expression of plasma membrane calcium ATPase 2 and collapsin response mediator protein 1 promotes death of spinal cord neurons. Cell Death Differ 2010, 17, 1501-1510
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Ago, T., Kuroda, J., Pain, J., Fu, C., Li, H., Sadoshima, J., Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res 2010, 106, 1253-1264
- Locke, D.,
Bian, S., Li, H., Harris, A. L., Post-translational modifications of
connexin26 revealed by mass spectrometry. Biochem J 2009, 424, 385-398
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Fu,
C., Wu, C., Liu, T., Ago, T., Zhai, P., Sadoshima, J. , et
al. , Elucidation of thioredoxin target protein networks
in mouse. Mol Cell Proteomics 2009, 8 , 1674-1687
- Jain,
M. R., Bian, S., Liu, T., Hu, J., Elkabes, S., Li, H., Altered proteolytic
events in experimental autoimmune encephalomyelitis discovered by itraq
shotgun proteomics analysis of spinal cord. Proteome Sci 2009,
7 , 25
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Liu, T., Hu, J., Li, H., in: Ottens, A. K., Wang, K. K. W. (Eds.), iTRAQ-Based
Shotgun Neuroproteomics, Neuro Proteomics, Methods in Molecular
Biology , Humana Press, Totowa 2009, p. 322.
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- Selvamurugan,
N., Shimizu, E., Lee, M., Liu, T., Li, H., Partridge, N. C., Identification
and characterization of runx2 phosphorylation sites involved in matrix
metalloproteinase-13 promoter activation . FEBS Lett 2009,
583 , 1141-1146
- Tyler,
W. A., Gangoli, N., Gokina, P., Kim, H. A., Covey, M., Levison, S. W.
, et al. , Activation of the mammalian target of rapamycin
(mtor) is essential for oligodendrocyte differentiation . J Neurosci
2009, 29 , 6367-6378
- Wang,
J., Leone, P., Wu, G., Francis, J. S., Li, H., Jain, M. R. , et
al. , Myelin lipid abnormalities in the aspartoacylase-deficient
tremor rat . Neurochem Res 2009, 34 , 138-148
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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.
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Fu,
C., Hu, J., Liu, T., Ago, T., Sadoshima, J., Li, H., Quantitative
analysis of redox-sensitive proteome with DIGE and ICAT .
J Proteome Res 2008, 7 , 3789-3802 NIHMSID # 74926.
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Wang,
Y., Liu, T., Wu, C., Li, H., A strategy for direct identification
of protein S-nitrosylation sites by quadrupole time-of-flight mass
spectrometry. J Am Soc Mass Spectrom 2008, 19, 1353-1360 NIHMSID #
70267
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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 NIHMSID # 51893.
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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 NIHMSID # 51848.
- Wannemacher,
K. M., Terskiy, A., Bian, S., Yadav, P. N., Li, H., Howells, R. D.,
Purification and mass spectrometric analysis of the kappa opioid receptor.
Brain Res 2008, 1230, 13-26
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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.
- Li,
W., Yu, S., Liu, T., Kim, J. H., Blank, V., Li, H., Kong, A. N., Heterodimerization
with small Maf proteins enhances nuclear retention of Nrf2 via masking
the NESzip motif. Biochim Biophys Acta 2008, 1783, 1847-1856
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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
PMCID: PMC2435290.
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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 PMCID: PMC2430926.
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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.
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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.
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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.
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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.
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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 PMCID: PMC2553677.
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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 PMCID:
PMC2423279.
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Das,
A., Li, H., Liu, T., Bellofatto, V., Biochemical characterization
of Trypanosoma brucei RNA polymerase II . Mol Biochem Parasitol
2006, 150 , 201-210.
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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.
2005
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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