Rong Wang, PhD

Biological mass spectrometry, proteomics, metabolomics and systems biology

Research in my laboratory is focused on biological mass spectrometry and mass spectrometry based proteomics and metabolomics.  We develop and utilize mass spectrometry technology to probe the protein interactions and protein processing mechanisms of the amyloid beta-protein in Alzheimer's disease. We are continuously developing new mass spectrometric methodologies in conjunction with protein purification technologies in order to increase protein detection sensitivity, enhance identification and characterization of protein post-translational modifications and perform quantification of particular protein sets (also known as proteome). This methodological development has been extensively applied to (1) the study of proteomics of cellular vesicle trafficking; (2) the study of protein secretion, trafficking and degradation; (3) the cellular proteomics of Alzheimer's disease as well as (4) metabolomics.  It is our goal to continue to use biological mass spectrometry as an analytical tool to further our understanding of the molecular mechanisms of Alzheimer's disease, neuron degenerative diseases and cancer.

We are currently conducting researches in the following four general areas:

-Proteomics and metabolomics studies of neurodegenerative disease, cancer and other human diseases. Proteins and metabolites from different stages of disease are systematically analyzed using mass spectrometry to discover disease specific biomarkers as well as to understand disease pathological mechanisms.  Currently we are conducing plasma proteomics of Alzheimer's disease and tissue proteomics of hepatocellular carcinoma.  Based on the protein profile changes, we will modeling how metabolic pathways are altered in pathological conditions and further conducting metabolomics studies for comprehensively understand disease mechanisms.

-Proteomics study of intracellular vesicle trafficking.  Two cellular processes, endocytosis and exocytosis, are investigated by proteomics approaches.  The newly developed subcellular fractionation methodologies and mass spectrometry allow us to study these dynamic processes in great detail.  Currently, we are investigating the endocytosis pathways by applying magnetic nano-particles and stable isotope labeling techniques together with mass spectrometry.  

-Investigation of biological processes involving the synthesis, modification, and degradation of biological peptides and proteins using modern mass spectrometric methods. In recent years there has been a great amount of interest in investigating the biochemical events involved in the regulation of protein processing and metabolism as well as the disruption of these processes, for example, the processing of beta-amyloid precursor protein and metabolism of amyloid beta-peptide in Alzheimer's disease.

-Study of protein posttranslational modifications and their role in human diseases using mass spectrometry. We arefocusing on developing more sensitive methods using mass spectrometry to identify the type, the number and the site of protein posttranslational modifications, for examples phosphorylation.

Wang R, Chen L, Cotter RJ. Effects of peptide hydrophobicity and charge state on molecular ion yields in plasma desorption mass spectrometry. Analytical chemistry 1990 Aug; 62(15).

Wang R, Meschia JF, Cotter RJ, Sisodia SS. Secretion of the beta/A4 amyloid precursor protein. Identification of a cleavage site in cultured mammalian cells. The Journal of biological chemistry 1991 Sep; 266(25).

Chait BT, Wang R, Beavis RC, Kent SB. Protein ladder sequencing. Science (New York, N.Y.) 1993 Oct; 262(5130).

Wang R, Sweeney D, Gandy SE, Sisodia SS. The profile of soluble amyloid beta protein in cultured cell media. Detection and quantification of amyloid beta protein and variants by immunoprecipitation-mass spectrometry. The Journal of biological chemistry 1996 Dec; 271(50).

Borchelt DR, Thinakaran G, Eckman CB, Lee MK, Davenport F, Ratovitsky T, Prada CM, Kim G, Seekins S, Yager D, Slunt HH, Wang R, Seeger M, Levey AI, Gandy SE, Copeland NG, Jenkins NA, Price DL, Younkin SG, Sisodia SS. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 1996 Nov; 17(5).

Xu H, Gouras GK, Greenfield JP, Vincent B, Naslund J, Mazzarelli L, Fried G, Jovanovic JN, Seeger M, Relkin NR, Liao F, Checler F, Buxbaum JD, Chait BT, Thinakaran G, Sisodia SS, Wang R, Greengard P, Gandy S. Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides. Nature medicine 1998 Apr; 4(4).

Lichtenthaler SF, Wang R, Grimm H, Uljon SN, Masters CL, Beyreuther K. Mechanism of the cleavage specificity of Alzheimer's disease gamma-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. Proceedings of the National Academy of Sciences of the United States of America 1999 Mar; 96(6).

Murphy MP, Hickman LJ, Eckman CB, Uljon SN, Wang R, Golde TE. gamma-Secretase, evidence for multiple proteolytic activities and influence of membrane positioning of substrate on generation of amyloid beta peptides of varying length. The Journal of biological chemistry 1999 Apr; 274(17).

Wang R, Chait BT, Wolf I, Kohanski RA, Cardozo C. Lysozyme degradation by the bovine multicatalytic proteinase complex (proteasome): evidence for a nonprocessive mode of degradation. Biochemistry 1999 Nov; 38(44).

Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, Sambamurti K, Duff K, Pappolla MA. Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiology of disease 2000 Aug; 7(4).

Dias DC, Dolios G, Wang R, Pan ZQ. CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex. Proceedings of the National Academy of Sciences of the United States of America 2002 Dec; 99(26).

Brasaemle DL, Dolios G, Shapiro L, Wang R. Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes. The Journal of biological chemistry 2004 Nov; 279(45).

Omenn GS, States DJ, Adamski M, Blackwell TW, Menon R, Hermjakob H, Apweiler R, Haab BB, Simpson RJ, Eddes JS, Kapp EA, Moritz RL, Chan DW, Rai AJ, Admon A, Aebersold R, Eng J, Hancock WS, Hefta SA, Meyer H, Paik YK, Yoo JS, Ping P, Pounds J, Adkins J, Qian X, Wang R, Wasinger V, Wu CY, Zhao X, Zeng R, Archakov A, Tsugita A, Beer I, Pandey A, Pisano M, Andrews P, Tammen H, Speicher DW, Hanash SM. Overview of the HUPO Plasma Proteome Project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database. Proteomics 2005 Aug; 5(13).

Morón JA, Abul-Husn NS, Rozenfeld R, Dolios G, Wang R, Devi LA. Morphine administration alters the profile of hippocampal postsynaptic density-associated proteins: a proteomics study focusing on endocytic proteins. Molecular & cellular proteomics : MCP 2007 Jan; 6(1).

Rusinova R, Shen YM, Dolios G, Padovan J, Yang H, Kirchberger M, Wang R, Logothetis DE. Mass spectrometric analysis reveals a functionally important PKA phosphorylation site in a Kir3 channel subunit. Pflügers Archiv : European journal of physiology 2009 Jun; 458(2).

Abul-Husn NS, Bushlin I, Morón JA, Jenkins SL, Dolios G, Wang R, Iyengar R, Ma'ayan A, Devi LA. Systems approach to explore components and interactions in the presynapse. Proteomics 2009 Jun; 9(12).

Tong W, Chen Z, Cao Z, Wang Q, Zhang J, Bai X, Wang R, Liu S. Robustness analysis of a constraint-based metabolic model links cell growth and proteomics of Thermoanaerobacter tengcongensis under temperature perturbation. Molecular bioSystems 2013 Apr; 9(4).

Mendoza J, Sekiya M, Taniguchi T, Iijima KM, Wang R, Ando K. Global analysis of phosphorylation of tau by the checkpoint kinases Chk1 and Chk2 in vitro. Journal of proteome research 2013 Jun; 12(6).

Wang Y, Kou Y, Wang X, Cederbaum A, Wang R. Multifactorial comparative proteomic study of cytochrome P450 2E1 function in chronic alcohol administration. PloS one 2014; 9(3).