The primary interest of my laboratory is to understand the molecular and biochemical events leading to pathological aging and the early development of cancer. Traditionally, single proteins have commonly been chosen to study a variety of biological problems, but proteins cannot function alone and their physiological and biochemical properties are completely dependent on their interactions with other molecules. As a result, my laboratory recently has decided to study the function and integration of the entire biochemical circuitry that modulates the progression of aging and cancer using a series of newly developed mass spectrometric and proteomic technologies to address the following areas:
- Analyzing changes in protein expression of the whole proteome or in particular subcellular compartments during the initial stages of cancer and pathological aging.
- Elucidating the protein-protein interaction pathways that are involved in altering cancer cell signaling and cellular aging.
- Identifying the alteration of protein structure and post-translational modifications that lead to the dysregulation of signaling modules during the course of aging and early cancer development.
Lab Techniques and Equipment
- Mass Spectrometers (LTQ ion trap and LTQ-Orbitrap hybrid mass spectrometers)
- Analyses of marcromolecular complexes and post-translational modifications by stable isotope labeling and chemical cross-linking.
- Capillary and multiple dimensional nano-HPLC
- Free flow electrophoresis (Isoelectric focusing and zone electrophoresis)
- Bioinformatics (software development for database search and quantitative proteomic analyses)
Biological mass spectrometry and post-translation modifications of age-related neurodegeneration
- Thomas ST, Funk KE, Wan Y, Liao Z, Davies P, Kuret J and Yang AJ. Dual modification of Alzheimer’s disease PHF-tau protein by lysine methylation and ubiquitylation: a mass spectrometry approach. Acta Neuropatholgica (2012) 123(1):105-17.
- Cripps D, Thomas SN, and Davies P and Yang AJ. Alzheimer's disease specific conformation of hyperphosphorylated PHF-tau is polyubiquitinated through lys-48, lys-11, and lys-6 ubiquitin conjugation. Journal of Biological Chemistry (2006); 281(16):10825-38.
- Shaw J, Chio J, Dasgupta S, Lai A, Mo G, Pang F, Thomason L, Yang A; Yip C; Nitz M, and McLaurin J. Aβ(1-42) assembly in the presence of scyllo-Inositol derivatives: Identification of an oxime linkage as important for the development of assembly inhibitors. ACS Chemical Neuroscience. Web Publication Date: December 23, 2011
- Tekirian, TL, Thomas, SN and Yang AJ. Advancing signaling networking through proteomics. Expert Review of Proteomics (2007); 4:573-83.
- Thomas SN, Soreghan BA, Head E, and Yang AJ. Reduced expression of synaptic transmission modulator HNK-1/ Neural Cell Adhesion Molecule (NCAM) as a consequence of Aß-mediated oxidative stress: a proteomic approach. Journal of Neurochemistry (2005); 92(4):705-17
- Liao Z, Wan Y, Thomas SN, Ann DK, and Yang AJ. IsoQuant: A new software tool for SILAC-based mass spectrometry quantitation. Analytical Chemistry (2012) 2012 Apr 20. [Epub ahead of print]. PMID:22519468.
- Thomas SN, Wan Y, Liao Z, Hanson PI, Yang AJ. Stable isotope labeling with amino acids in cell culture based mass spectrometry approach to detect transient protein interactions using substrate trapping. Analytical Chemistry (2011); 83(14): 5511-8.
- Wan Y, Yang A and Chen T. PepHMM: A hidden Markov model based scoring function for mass spectrometry database search. Journal of Analytical Chemistry (2006); 78(2):432-7
- Wan, Y, Cripps, D, Thomas S, Campbell, P, Ambulos, N, Chen, T, and Yang AJ. PhosphoScan: A probability-based method for phosphorylation site prediction using MS2/MS3 pair information. Journal of Proteomics Research (2008); 7: 2803-11.
Cancer and genomic instability
- Lin HH, Li X, Chen JL, Sun XZ, Cooper FN, Zhang YU, Li A, Chen YR, Chun-Ting, Cheng CT, Yang LX, Deng XT, Liu XY, Yen Y, Johnson DL, Shih HM, Yang AJ, and Ann DK. Hypoxia Induces AAA-ATPase VPS4B Degradation, Promoting EGFR Abundance and Signaling. Molecular Biology of Cell (2012) 32(6):1124-38.
- Thomas SN, Morgan WF, Yang AJ and Baulch J. Quantitative Proteomic Analysis of Mitochondrial Proteins Reveals Pro-Survival Mechanisms in the Perpetuation of Radiation Induced Genomic Instability. Free Radical Biology and Medicine (2012) DOI information: 10.1016/j.freeradbiomed.2012.03.025. Accepted manuscript (unedited version) available online: 19-APR-2012. *Co-corresponding author.
- Vijayakumar S, Dziegielewska B, Levin DS, Wei Song W, Yin J, Yang AJ, Matsumoto Y, Vladimir P. Bermudez VP, Hurwitz J. and Tomkinson AE. Phosphorylation of Human DNA Ligase I Regulates its Interaction with Replication Factor C and its Participation in DNA Replication and DNA Repair. Molecular and Cellular Biology (2009); 29(8):2042-52.
- Miller, JH, Jin, S, Morgan, W, Yang AJ, Wan,Y Peters, JS and Springer DL. Profiling mitochondrial proteins in radiation-Induced genome-unstable cell lines by mass spectrometry. Radiation Research (2008); 69(6):700-6.
- Lee YK, Thomas SN, Yang AJ and Ann DK. Doxorubicin downregulates KAP1 SUMOylation that relieves its transcription repression on p21WAF1/CIP1 in breast cancer MCF-7 cells. Journal of Biological Chemistry (2007); 282(3):1595-606.