Proteomics provides an unbiased window on the workings of the cell, and can provide cues to functional protein complexes, biomarkers and potential therapeutic targets. Three projects are:
1. More than a quarter of those infected with HIV exhibit some form of cognitive impairment. The Einstein Proteomics Research Center for HIV-Related Neurological and Substance Abuse is investigating the mechanisms underlying the development of cognitive impairment in HIV infected individuals even in the face of modern CART therapy. Quantitative proteomics technologies are being used in animal and tissue culture models and in human subjects, in a collaboration with Drs. Harris Goldstein, Joan Berman, Andras Fiser, Louis Weiss and Julia Arnsten. These studies will help identify new therapeutic targets for preventing the progression neurological consequences of AIDS.
2. Proteomic studies of the development of hepatic neoplasia in rat are being translated into studies with human patients. Serum biomarkers are being identified to help identify patients with early stage hepatocellular carcinoma in a collaboration with Drs. Allan Wolkoff and Milan Kinkhabwala. Our laboratory has also developed proteomic tools for identification of tubulin isotypes and posttranslational modifications. These tools are being used to identify changes in tubulin composition associated with development of metastasis or drug resistance, in collaboration with Dr. Susan Band Horwitz.
3. Our laboratory probes protein dynamics and protein complexes in solution using the tools of hydrogen-deuterium exchange coupled to mass spectrometry and novel technologies for enrichment of crosslinked partners at protein contact sites. The details of molecular structure and interactions reveal mechanistic insights.
Link to NIHMS profile:
Carvallo L, Lopez L, Che FY, Lim J, Eugenin EA, et al. Buprenorphine Decreases the CCL2 –Mediated Chemotactic Response of Monocytes. J Immunol. 2 01 5 Apr 1 ;1 94(7 ):32 46-58. PMC4369415
Harris TM, Du P, Kawachi N, Belbin TJ, Wang Y, et al. Proteomic analysis of oral cavity squamous cell carcinoma specimens identifies patient outcome-associated proteins. Arch Pathol Lab Med. 2015 Apr;1 3 9(4):494-507 PMC4380852 .
Nika H, Angeletti RH, Hawke DH. N-term inal protein characterization by m ass spectrom etry using combined microscale liquid and solid-phase derivatization. J Biomol Tech. 2 014 Sep;2 5(3 ):77-86. PMC436438
Nika H, Hawke DH, Angeletti RH. N-terminal protein characterization by mass spectrometry after cyanogens bromide cleav age using com bined m icroscale liquid- and solid-phase deriv atization. J Biomol Tech. 2014 Apr;2 5(1 ):1 9-3 0. PMC3942260.
Tarassishin L, Lim J, Weatherly DB, Angeletti RH, Lee SC. Interleukin-1-induced changes in the glioblastoma secretome suggest its role in tumor progression. J Proteomics. 2014 Mar 1 7 ;99:1 52 -68. PMC3 977979.
Lim J, Liu Z, Apontes P, Feng D, Pessin JE, et al. Dual mode action of mangiferin in mouse liver under high fat diet. PLoS One. 2014;9(3 ):e90137 PMC3 943915.
Albrethsen J, Angeletti RH, Horwitz SB, Yang CP. Proteomics of cancer cell lines resistant to microtubulestabilizing agents. Mol Cancer Ther. 2014 Jan;1 3 (1 ):2 60-9. PMC3 947109
Nardelli SC, Che FY, Silmon de Monerri NC, Xiao H, Nieves E, et al. The histone code of Toxoplasm a gondii comprises conserved and unique posttranslational modifications. MBio. 2 01 3 Dec 1 0;4(6):e0092 2 -1 3 PMC3870261
L Miller, A Menthena, C Chatterjee, P Verdier-Pinard, P Novikoff, SB Horwitz, R Hogue Angeletti (2008) Identification of a Unique Post-Translational Modification of the β IVb-Tubulin Isotype that has Increased Expression in Liver Cancer, Biochemistry 47, 7572-7582.
JM Dybas, CM Madrid-Aliste, FY Che, E Nieves, D Rykunov, R Hogue Angeletti, LM Weiss, K Kim, A Fiser.(2008) Computational Analysis and Experimental Validation of Gene Predictions in Toxoplasma gondii. PLoS ONE 3(12): e3899 doi:10.1371/journal.pone.0003899
C Madrid-Aliste, JM Dybas, R Hogue Angeletti, LM Weiss, K Kim, I Simon and A Fiser. EPIC-DB: a proteomics database for studying Apicomplexan organisms (2009) BMC Genomics 10:38
LM Weiss, A Fiser, R Hogue Angeletti, K Kim (2009) Toxoplasma gondii Proteomics, Expert Reviews in Mass Spectrometry, 6, 303-313
WD Zencheck, H Xiao, BJ Nolen, R Hogue Angeletti, TD Pollard, SC Almo (2009) Nucleotide and activator-dependent structural and dynamic changes of Arp2/3 complex monitored by hydrogen/deuterium exchange and mass spectrometry. J Mol Biol 390, 414-427
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