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Wei-Jen Tang

InstitutionUniversity of Chicago
DepartmentBen May Department of Cancer Research
AddressChicago IL 60637
Phone+1 (773) 702-4331
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    Collapse Overview 
    Collapse overview
    My laboratory focuses on applying integrated structural and biochemical approaches to elucidate the molecular basis of protein-protein interactions and protein-ligand/drug interactions that are relevant to human health and diseases. Armed with such knowledge, we then apply chemical and pharmacological approaches to develop therapeutic innovations. Currently, we are studying the following proteins:

    Amyloid peptide-degrading proteases: Metalloproteases, insulin degrading enzyme (IDE) and presequence protease (PreP) degrade amyloid beta, a peptide vital for the progression of Alzheimer's disease. IDE is also involved in the clearance of insulin, amylin, and glucagon, pancreatic peptides for glucose homeostasis. PreP is involved in the clearance of mitochondrial importing presequence peptides, which are toxic to mitochondria. Our structures of human IDE in complex with its substrates elucidate the molecular basis of how IDE recognizes amyloidogenic peptides and offers a basis to explore IDE-based therapeutics in controlling cerebral amyloid beta accumulation and blood sugar levels. Our structures of human PreP reveal how PreP recognizes amyloid beta. Future directions in studying proteases that degrade amyloid peptides include exploration into the molecular basis in the regulation of catalysis of IDE, PreP, and other amyloid-peptide degrading proteases such as neprilysin and endothelin converting enzymes, discovery of small molecule activator and inhibitor leads, and protein engineering for therapies.

    Chemokines: Inflammation is vital in the progression of many chronic human illnesses. Proinflammatory chemokines, e.g., CCL5 and CCL3, play key roles in modulating inflammation and consequently affect disease progression such as cancer and immunological disorders. In addition, CCR5, the CCL3 and CCL5 cognate receptor, is a co-receptor for HIV virus. Self-association and binding to extracellular glycan of chemokines are key regulatory steps in controlling chemokine functions. Our structural and biochemical analyses of CCL3 and CCL5 have elucidated the structural basis of CCL3 and CCL5 oligomerization and binding to glycosaminoglycan (GAG). Future directions include the elucidation of the molecular basis of how oligomerization and GAG binding regulates chemokine functions and the development of small molecules to modulate inflammation.

    Bacterial toxins secreted by human bacterial pathogens: We study bacterial adenylyl cyclase toxins that are only active upon entering into target cells and are associated with cellular proteins that serve as the activator. These adenylyl cyclase toxins raise the intracellular cyclic AMP (cAMP) of their host cells to benefit bacterial propagation. We have studied three adenylyl cyclase toxins, edema factor (EF) secreted by bacteria that cause anthrax, CyaA secreted bacteria that cause whooping cough, and ExoY injected by Pseudomonas aeruginosa, an opportunistic pathogens for nosocomial infections. Both EF and CyaA bind the cellular calcium sensor, calmodulin, with high affinity. Our structural and biochemical analyses have elucidated how calmodulin binds and activates EF and CyaA. ExoY is activated by binding to F-actin and we show that ExoY induces the bundling of F-actin. We will continue to address the structural basis for the interaction of these toxins with their cellular partners. We will also explore the therapeutic potential of adenylyl cyclase toxins in human diseases as well. The incident of bioterrorism-related anthrax in 2001 has moved the challenge against anthrax from an obscure agricultural problem to the center of bio-defense. Given the ease of making antibiotic-resistant anthrax strains and unknown enemies, the best defense against anthrax is to build up a battery of possible antidotes against anthrax that can be rapidly scaled up for production in response to the low probability, high impact incidence of anthrax-related bioterrorism.

    Collapse Biography 
    Collapse education and training
    National Taiwan University, Taipei, TaiwanB.S.06/1982Zoology
    Taiwanese Air Force, TaiwanFirst Lieutenant08/1984
    University of Texas, Austin, Austin, TexasPhD06/1988Biological Sciences
    University of Texas Austin, Austin, TexasPostdoctoral fellow08/1988Virology
    University of Texas Southwestern Medical School, Dallas, TexasPostdoctoral fellow06/1993Pharmacology
    Collapse awards and honors
    1999 - 2002Established Investigator, American Heart Association
    1995 - 1996Young Investigator, Cancer Research Foundation
    1983 - 1984University fellowship, University of Texas, Austin

    Collapse Research 
    Collapse research activities and funding
    R01GM121964     (TANG, WEI-JEN)Sep 1, 2017 - Aug 31, 2025
    Integrative structural analysis of human insulin degrading enzyme
    Role: Principal Investigator

    Grant-in-Aid 17GRNT33400028     (Tang, Wei-Jen)Jan 1, 2017 - Dec 31, 2018
    American Heart Association
    Structure and functions of chemokine CCL5-CXCL4 hetero-oligomer
    Role Description: This study is to use biophysical and structural methods to investigate the molecular basis of heteromer formation between CCL5 and CXCL4.
    Role: Principal Investigator

    R01GM081539     (TANG, WEI-JEN)Jul 15, 2007 - Aug 31, 2016
    Regulation and Catalysis of Human Insulin Degrading Enzyme
    Role: Principal Investigator

    R01AI066503     (TANG, WEI-JEN)Feb 15, 2005 - Jul 31, 2006
    Intervention against anthrax edema factor (EF)
    Role: Principal Investigator

    R01GM062548     (TANG, WEI-JEN)Mar 1, 2001 - Mar 31, 2011
    Calmodulin-Activated Adenylyl Cyclase Toxins
    Role: Principal Investigator

    R01GM053459     (TANG, WEI-JEN)Sep 1, 1996 - Aug 31, 2004
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Liang WG, Mancl JM, Zhao M, Tang WJ. Structural analysis of Mycobacterium tuberculosis M13 metalloprotease Zmp1 open states. Structure. 2021 07 01; 29(7):709-720.e3. PMID: 33378640; PMCID: PMC8691456.
      Citations: 3     Fields:    Translation:Cells
    2. Mancl JM, Suarez C, Liang WG, Kovar DR, Tang WJ. Pseudomonas aeruginosa exoenzyme Y directly bundles actin filaments. J Biol Chem. 2020 03 13; 295(11):3506-3517. PMID: 32019868; PMCID: PMC7076225.
      Citations: 5     Fields:    Translation:Cells
    3. Li NS, Liang W, Piccirilli JA, Tang WJ. Reinvestigating the synthesis and efficacy of small benzimidazole derivatives as presequence protease enhancers. Eur J Med Chem. 2019 Dec 15; 184:111746. PMID: 31610373; PMCID: PMC6874713.
      Citations: 2     Fields:    Translation:HumansCells
    4. Leroux F, Bosc D, Beghyn T, Hermant P, Warenghem S, Pottiez V, Guillaume V, Charton J, Herledan A, Urata S, Liang W, Sheng L, Tang WJ, Deprez B, Deprez-Poulain R, Landry V. Identification of ebselen as a potent inhibitor of insulin degrading enzyme by a drug repurposing screening. Eur J Med Chem. 2019 Oct 01; 179:557-566. PMID: 31276900; PMCID: PMC6718346.
      Citations: 9     Fields:    Translation:HumansCells
    5. Farcasanu M, Wang AG, Uchanski T, Bailey LJ, Yue J, Chen Z, Wu X, Kossiakoff A, Tang WJ. Rapid Discovery and Characterization of Synthetic Neutralizing Antibodies against Anthrax Edema Toxin. Biochemistry. 2019 07 09; 58(27):2996-3004. PMID: 31243996; PMCID: PMC6659421.
      Citations: 1     Fields:    Translation:HumansAnimalsCells
    6. Lai R, Tang WJ, Li H. Catalytic Mechanism of Amyloid-ß Peptide Degradation by Insulin Degrading Enzyme: Insights from Quantum Mechanics and Molecular Mechanics Style Møller-Plesset Second Order Perturbation Theory Calculation. J Chem Inf Model. 2018 09 24; 58(9):1926-1934. PMID: 30133282; PMCID: PMC6670292.
      Citations: 3     Fields:    Translation:Cells
    7. Zhang Z, Liang WG, Bailey LJ, Tan YZ, Wei H, Wang A, Farcasanu M, Woods VA, McCord LA, Lee D, Shang W, Deprez-Poulain R, Deprez B, Liu DR, Koide A, Koide S, Kossiakoff AA, Li S, Carragher B, Potter CS, Tang WJ. Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme. Elife. 2018 03 29; 7. PMID: 29596046; PMCID: PMC5910022.
      Citations: 23     Fields:    Translation:HumansCells
    8. Bailey LJ, Sheehy KM, Dominik PK, Liang WG, Rui H, Clark M, Jaskolowski M, Kim Y, Deneka D, Tang WJ, Kossiakoff AA. Locking the Elbow: Improved Antibody Fab Fragments as Chaperones for Structure Determination. J Mol Biol. 2018 02 02; 430(3):337-347. PMID: 29273204; PMCID: PMC5800945.
      Citations: 29     Fields:    Translation:HumansAnimalsCells
    9. Sharma S, Galanina N, Guo A, Lee J, Kadri S, Van Slambrouck C, Long B, Wang W, Ming M, Furtado LV, Segal JP, Stock W, Venkataraman G, Tang WJ, Lu P, Wang YL. Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL. Oncotarget. 2016 Oct 18; 7(42):68833-68841. PMID: 27626698; PMCID: PMC5356593.
      Citations: 37     Fields:    Translation:HumansCells
    10. Yue J, Zhang Y, Liang WG, Gou X, Lee P, Liu H, Lyu W, Tang WJ, Chen SY, Yang F, Liang H, Wu X. In vivo epidermal migration requires focal adhesion targeting of ACF7. Nat Commun. 2016 05 24; 7:11692. PMID: 27216888; PMCID: PMC5476826.
      Citations: 27     Fields:    Translation:HumansAnimalsCells
    11. Liang WG, Triandafillou CG, Huang TY, Zulueta MM, Banerjee S, Dinner AR, Hung SC, Tang WJ. Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3. Proc Natl Acad Sci U S A. 2016 May 03; 113(18):5000-5. PMID: 27091995; PMCID: PMC4983845.
      Citations: 41     Fields:    Translation:HumansCells
    12. Tang WJ. Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus. Trends Endocrinol Metab. 2016 Jan; 27(1):24-34. PMID: 26651592; PMCID: PMC4698235.
      Citations: 49     Fields:    Translation:HumansAnimals
    13. Deprez-Poulain R, Hennuyer N, Bosc D, Liang WG, Marechal X, Charton J, Totobenazara J, Berte G, Jahklal J, Verdelet T, Dumont J, Dassonneville S, Woitrain E, Gauriot M, Paquet C, Duplan I, Hermant P, Landry V, Herledan A, Piveteau C, Leroux F, Tang WJ, Staels B, Deprez B, Enée E, Cantrelle FX, Sevin E, Culot M, Lippens G, van Endert P. Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice. Nat Commun. 2015 Sep 23; 6:8250. PMID: 26394692; PMCID: PMC4580987.
      Citations: 41     Fields:    Translation:HumansAnimalsCells
    14. Tang WJ, Urbauer RJ, Moskovitz J, Urbauer JL, Seifert R, Lübker C, Dove S. Different Roles of N-Terminal and C-Terminal Domains in Calmodulin for Activation of Bacillus anthracis Edema Factor. Toxins (Basel). 2015 Jul 13; 7(7):2598-614. PMID: 26184312; PMCID: PMC4516931.
      Citations: 2     Fields:    Translation:Cells
    15. Liang WG, Ren M, Zhao F, Tang WJ. Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme. J Mol Biol. 2015 Mar 27; 427(6 Pt B):1345-1358. PMID: 25636406; PMCID: PMC4355285.
      Citations: 17     Fields:    Translation:HumansCells
    16. Charton J, Gauriot M, Totobenazara J, Hennuyer N, Dumont J, Bosc D, Marechal X, Elbakali J, Herledan A, Wen X, Ronco C, Gras-Masse H, Heninot A, Pottiez V, Landry V, Staels B, Liang WG, Leroux F, Tang WJ, Deprez B, Deprez-Poulain R. Structure-activity relationships of imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme. Eur J Med Chem. 2015 Jan 27; 90:547-67. PMID: 25489670; PMCID: PMC4325277.
      Citations: 9     Fields:    Translation:HumansCells
    17. King JV, Liang WG, Scherpelz KP, Schilling AB, Meredith SC, Tang WJ. Molecular basis of substrate recognition and degradation by human presequence protease. Structure. 2014 Jul 08; 22(7):996-1007. PMID: 24931469; PMCID: PMC4128088.
      Citations: 16     Fields:    Translation:HumansCells
    18. Tanaka-Matakatsu M, Miller J, Borger D, Tang WJ, Du W. Daughterless homodimer synergizes with Eyeless to induce Atonal expression and retinal neuron differentiation. Dev Biol. 2014 Aug 15; 392(2):256-65. PMID: 24886829; PMCID: PMC4106475.
      Citations: 11     Fields:    Translation:AnimalsCells
    19. Maianti JP, McFedries A, Foda ZH, Kleiner RE, Du XQ, Leissring MA, Tang WJ, Charron MJ, Seeliger MA, Saghatelian A, Liu DR. Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones. Nature. 2014 Jul 03; 511(7507):94-8. PMID: 24847884; PMCID: PMC4142213.
      Citations: 86     Fields:    Translation:AnimalsCells
    20. Charton J, Gauriot M, Guo Q, Hennuyer N, Marechal X, Dumont J, Hamdane M, Pottiez V, Landry V, Sperandio O, Flipo M, Buee L, Staels B, Leroux F, Tang WJ, Deprez B, Deprez-Poulain R. Imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, substrate-dependent modulators of insulin-degrading enzyme in amyloid-ß hydrolysis. Eur J Med Chem. 2014 May 22; 79:184-93. PMID: 24735644; PMCID: PMC4128174.
      Citations: 16     Fields:    Translation:HumansCells
    21. McCord LA, Liang WG, Dowdell E, Kalas V, Hoey RJ, Koide A, Koide S, Tang WJ. Conformational states and recognition of amyloidogenic peptides of human insulin-degrading enzyme. Proc Natl Acad Sci U S A. 2013 Aug 20; 110(34):13827-32. PMID: 23922390; PMCID: PMC3752249.
      Citations: 29     Fields:    Translation:HumansCells
    22. Tripathi A, Saini V, Marchese A, Volkman BF, Tang WJ, Majetschak M. Modulation of the CXC chemokine receptor 4 agonist activity of ubiquitin through C-terminal protein modification. Biochemistry. 2013 Jun 18; 52(24):4184-92. PMID: 23697661; PMCID: PMC4113718.
      Citations: 18     Fields:    Translation:HumansAnimalsCells
    23. Taha H, Dove S, Geduhn J, Shen Y, Tang WJ, Seifert R, König B. Inhibition of the adenylyl cyclase toxin, edema factor, from Bacillus anthracis by a series of 18 mono- and bis-(M)ANT-substituted nucleoside 5'-triphosphates. Naunyn Schmiedebergs Arch Pharmacol. 2012 Jan; 385(1):57-68. PMID: 21947230.
      Citations: 9     Fields:    Translation:Cells
    24. Dumetz F, Khun H, Glomski IJ, Corre JP, Tang WJ, Huerre M, Goossens PL, Jouvion G, Rougeaux C, Mock M. Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax. Am J Pathol. 2011 Jun; 178(6):2523-35. PMID: 21641378; PMCID: PMC3124019.
      Citations: 34     Fields:    Translation:AnimalsCellsPHPublic Health
    25. Cortright JJ, Lorrain DS, Beeler JA, Tang WJ, Vezina P. Previous exposure to delta9-tetrahydrocannibinol enhances locomotor responding to but not self-administration of amphetamine. J Pharmacol Exp Ther. 2011 Jun; 337(3):724-33. PMID: 21389094; PMCID: PMC3101004.
      Citations: 8     Fields:    Translation:Animals
    26. Ralat LA, Kalas V, Zheng Z, Goldman RD, Sosnick TR, Tang WJ. Ubiquitin is a novel substrate for human insulin-degrading enzyme. J Mol Biol. 2011 Feb 25; 406(3):454-66. PMID: 21185309; PMCID: PMC3064465.
      Citations: 19     Fields:    Translation:HumansCells
    27. Ralat LA, Guo Q, Ren M, Funke T, Dickey DM, Potter LR, Tang WJ. Insulin-degrading enzyme modulates the natriuretic peptide-mediated signaling response. J Biol Chem. 2011 Feb 11; 286(6):4670-9. PMID: 21098034; PMCID: PMC3039328.
      Citations: 33     Fields:    Translation:HumansCells
    28. Ren M, Guo Q, Guo L, Lenz M, Qian F, Koenen RR, Xu H, Schilling AB, Weber C, Ye RD, Dinner AR, Tang WJ. Polymerization of MIP-1 chemokine (CCL3 and CCL4) and clearance of MIP-1 by insulin-degrading enzyme. EMBO J. 2010 Dec 01; 29(23):3952-66. PMID: 20959807; PMCID: PMC3020635.
      Citations: 76     Fields:    Translation:HumansAnimalsCells
    29. Leissring MA, Malito E, Hedouin S, Reinstatler L, Sahara T, Abdul-Hay SO, Choudhry S, Maharvi GM, Fauq AH, Huzarska M, May PS, Choi S, Logan TP, Turk BE, Cantley LC, Manolopoulou M, Tang WJ, Stein RL, Cuny GD, Selkoe DJ. Designed inhibitors of insulin-degrading enzyme regulate the catabolism and activity of insulin. PLoS One. 2010 May 07; 5(5):e10504. PMID: 20498699; PMCID: PMC2866327.
      Citations: 59     Fields:    Translation:HumansAnimalsCells
    30. Bishop BL, Lodolce JP, Kolodziej LE, Boone DL, Tang WJ. The role of anthrolysin O in gut epithelial barrier disruption during Bacillus anthracis infection. Biochem Biophys Res Commun. 2010 Apr 02; 394(2):254-9. PMID: 20188700; PMCID: PMC4457453.
      Citations: 21     Fields:    Translation:HumansAnimalsCells
    31. Guo Q, Manolopoulou M, Bian Y, Schilling AB, Tang WJ. Molecular basis for the recognition and cleavages of IGF-II, TGF-alpha, and amylin by human insulin-degrading enzyme. J Mol Biol. 2010 Jan 15; 395(2):430-43. PMID: 19896952; PMCID: PMC2813390.
      Citations: 42     Fields:    Translation:HumansCells
    32. Ralat LA, Ren M, Schilling AB, Tang WJ. Protective role of Cys-178 against the inactivation and oligomerization of human insulin-degrading enzyme by oxidation and nitrosylation. J Biol Chem. 2009 Dec 04; 284(49):34005-18. PMID: 19808678; PMCID: PMC2797171.
      Citations: 23     Fields:    Translation:HumansAnimalsCells
    33. Hughes MA, Burns DL, Juris SJ, Tang WJ, Clement KH, Eaton LJ, Kelly-Cirino CD, McKee ML, Powell BS, Bishop BL, Rudge TL, Shine N, Verma A, Willis MS, Morse SA. The case for developing consensus standards for research in microbial pathogenesis: Bacillus anthracis toxins as an example. Infect Immun. 2009 Oct; 77(10):4182-6. PMID: 19651858; PMCID: PMC2747970.
      Citations: 1     Fields:    Translation:Humans
    34. Suryanarayana S, Wang JL, Richter M, Shen Y, Tang WJ, Lushington GH, Seifert R. Distinct interactions of 2'- and 3'-O-(N-methyl)anthraniloyl-isomers of ATP and GTP with the adenylyl cyclase toxin of Bacillus anthracis, edema factor. Biochem Pharmacol. 2009 Aug 01; 78(3):224-30. PMID: 19492438; PMCID: PMC2762704.
      Citations: 6     Fields:    Translation:Cells
    35. Chou YH, Kuo WL, Rosner MR, Tang WJ, Goldman RD. Structural changes in intermediate filament networks alter the activity of insulin-degrading enzyme. FASEB J. 2009 Nov; 23(11):3734-42. PMID: 19584300; PMCID: PMC2775012.
      Citations: 9     Fields:    Translation:AnimalsCells
    36. Tang WJ, Guo Q. The adenylyl cyclase activity of anthrax edema factor. Mol Aspects Med. 2009 Dec; 30(6):423-30. PMID: 19560485; PMCID: PMC2783455.
      Citations: 50     Fields:    Translation:HumansAnimalsCells
    37. Manolopoulou M, Guo Q, Malito E, Schilling AB, Tang WJ. Molecular basis of catalytic chamber-assisted unfolding and cleavage of human insulin by human insulin-degrading enzyme. J Biol Chem. 2009 May 22; 284(21):14177-88. PMID: 19321446; PMCID: PMC2682866.
      Citations: 43     Fields:    Translation:HumansCells
    38. Bourdeau RW, Malito E, Chenal A, Bishop BL, Musch MW, Villereal ML, Chang EB, Mosser EM, Rest RF, Tang WJ. Cellular functions and X-ray structure of anthrolysin O, a cholesterol-dependent cytolysin secreted by Bacillus anthracis. J Biol Chem. 2009 May 22; 284(21):14645-56. PMID: 19307185; PMCID: PMC2682912.
      Citations: 53     Fields:    Translation:HumansCells
    39. Taha HM, Schmidt J, Suryanarayana S, Shen Y, Tang WJ, Gille A, Geduhn J, Dove S, Seifert R, Göttle M, König B. Molecular analysis of the interaction of anthrax adenylyl cyclase toxin, edema factor, with 2'(3')-O-(N-(methyl)anthraniloyl)-substituted purine and pyrimidine nucleotides. Mol Pharmacol. 2009 Mar; 75(3):693-703. PMID: 19056899; PMCID: PMC2684916.
      Citations: 23     Fields:    Translation:AnimalsCells
    40. Malito E, Ralat LA, Manolopoulou M, Tsay JL, Wadlington NL, Tang WJ. Molecular bases for the recognition of short peptide substrates and cysteine-directed modifications of human insulin-degrading enzyme. Biochemistry. 2008 Dec 02; 47(48):12822-34. PMID: 18986166; PMCID: PMC2652632.
      Citations: 39     Fields:    Translation:HumansCells
    41. Kastrup CJ, Boedicker JQ, Pomerantsev AP, Moayeri M, Bian Y, Pompano RR, Kline TR, Sylvestre P, Shen F, Leppla SH, Tang WJ, Ismagilov RF. Spatial localization of bacteria controls coagulation of human blood by 'quorum acting'. Nat Chem Biol. 2008 Dec; 4(12):742-50. PMID: 19031531; PMCID: PMC2651025.
      Citations: 41     Fields:    Translation:HumansAnimalsCells
    42. Weirich G, Mengele K, Yfanti C, Gkazepis A, Hellmann D, Welk A, Giersig C, Kuo WL, Rosner MR, Tang WJ, Schmitt M. Immunohistochemical evidence of ubiquitous distribution of the metalloendoprotease insulin-degrading enzyme (IDE; insulysin) in human non-malignant tissues and tumor cell lines. Biol Chem. 2008 Nov; 389(11):1441-5. PMID: 18783335; PMCID: PMC3759010.
      Citations: 2     Fields:    Translation:HumansCells
    43. Yfanti C, Mengele K, Gkazepis A, Weirich G, Giersig C, Kuo WL, Tang WJ, Rosner M, Schmitt M. Expression of metalloprotease insulin-degrading enzyme insulysin in normal and malignant human tissues. Int J Mol Med. 2008 Oct; 22(4):421-31. PMID: 18813847; PMCID: PMC3675802.
      Citations: 14     Fields:    Translation:HumansCells
    44. Malito E, Hulse RE, Tang WJ. Amyloid beta-degrading cryptidases: insulin degrading enzyme, presequence peptidase, and neprilysin. Cell Mol Life Sci. 2008 Aug; 65(16):2574-85. PMID: 18470479; PMCID: PMC2756532.
      Citations: 80     Fields:    Translation:HumansAnimalsCells
    45. Guo Q, Jureller JE, Warren JT, Solomaha E, Tang WJ, Florián J. Protein-protein docking and analysis reveal that two homologous bacterial adenylyl cyclase toxins interact with calmodulin differently. J Biol Chem. 2008 Aug 29; 283(35):23836-45. PMID: 18583346; PMCID: PMC2527102.
      Citations: 14     Fields:    Translation:HumansCells
    46. Kuo SR, Willingham MC, Bour SH, Andreas EA, Park SK, Jackson C, Duesbery NS, Leppla SH, Tang WJ, Frankel AE. Anthrax toxin-induced shock in rats is associated with pulmonary edema and hemorrhage. Microb Pathog. 2008 Jun; 44(6):467-72. PMID: 18222626.
      Citations: 38     Fields:    Translation:AnimalsCells
    47. Warren JT, Guo Q, Tang WJ. A 1.3-A structure of zinc-bound N-terminal domain of calmodulin elucidates potential early ion-binding step. J Mol Biol. 2007 Nov 23; 374(2):517-27. PMID: 17942116; PMCID: PMC2128742.
      Citations: 13     Fields:    Translation:HumansCells
    48. Johnson EC, Malito E, Shen Y, Rich D, Tang WJ, Kent SB. Modular total chemical synthesis of a human immunodeficiency virus type 1 protease. J Am Chem Soc. 2007 Sep 19; 129(37):11480-90. PMID: 17705484.
      Citations: 21     Fields:    Translation:HumansCells
    49. Johnson EC, Malito E, Shen Y, Pentelute B, Rich D, Tang WJ, Kent SB, Florián J. Insights from atomic-resolution X-ray structures of chemically synthesized HIV-1 protease in complex with inhibitors. J Mol Biol. 2007 Oct 26; 373(3):573-86. PMID: 17869270; PMCID: PMC2094697.
      Citations: 7     Fields:    Translation:HumansCells
    50. Im H, Manolopoulou M, Malito E, Shen Y, Zhao J, Neant-Fery M, Sun CY, Meredith SC, Sisodia SS, Leissring MA, Tang WJ. Structure of substrate-free human insulin-degrading enzyme (IDE) and biophysical analysis of ATP-induced conformational switch of IDE. J Biol Chem. 2007 Aug 31; 282(35):25453-63. PMID: 17613531.
      Citations: 66     Fields:    Translation:HumansCells
    51. Li Q, Krogmann T, Ali MA, Tang WJ, Cohen JI. The amino terminus of varicella-zoster virus (VZV) glycoprotein E is required for binding to insulin-degrading enzyme, a VZV receptor. J Virol. 2007 Aug; 81(16):8525-32. PMID: 17553876; PMCID: PMC1951364.
      Citations: 22     Fields:    Translation:HumansCells
    52. Watson LE, Kuo SR, Katki K, Dang T, Park SK, Dostal DE, Tang WJ, Leppla SH, Frankel AE. Anthrax toxins induce shock in rats by depressed cardiac ventricular function. PLoS One. 2007 May 23; 2(5):e466. PMID: 17520025; PMCID: PMC1867860.
      Citations: 36     Fields:    Translation:Animals
    53. Hong J, Doebele RC, Lingen MW, Quilliam LA, Tang WJ, Rosner MR. Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1. J Biol Chem. 2007 Jul 06; 282(27):19781-7. PMID: 17491018.
      Citations: 45     Fields:    Translation:HumansCells
    54. Watson LE, Mock J, Lal H, Lu G, Bourdeau RW, Tang WJ, Leppla SH, Dostal DE, Frankel AE. Lethal and edema toxins of anthrax induce distinct hemodynamic dysfunction. Front Biosci. 2007 May 01; 12:4670-5. PMID: 17485403.
      Citations: 25     Fields:    Translation:HumansAnimals
    55. Firoved AM, Moayeri M, Wiggins JF, Shen Y, Tang WJ, Leppla SH. Anthrax edema toxin sensitizes DBA/2J mice to lethal toxin. Infect Immun. 2007 May; 75(5):2120-5. PMID: 17339348; PMCID: PMC1865792.
      Citations: 17     Fields:    Translation:AnimalsCells
    56. Shen Y, Joachimiak A, Rosner MR, Tang WJ. Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. Nature. 2006 Oct 19; 443(7113):870-4. PMID: 17051221; PMCID: PMC3366509.
      Citations: 166     Fields:    Translation:HumansCells
    57. Li P, Kuo WL, Yousef M, Rosner MR, Tang WJ. The C-terminal domain of human insulin degrading enzyme is required for dimerization and substrate recognition. Biochem Biophys Res Commun. 2006 May 19; 343(4):1032-7. PMID: 16574064.
      Citations: 26     Fields:    Translation:HumansCells
    58. Firoved AM, Miller GF, Moayeri M, Kakkar R, Shen Y, Wiggins JF, McNally EM, Tang WJ, Leppla SH. Bacillus anthracis edema toxin causes extensive tissue lesions and rapid lethality in mice. Am J Pathol. 2005 Nov; 167(5):1309-20. PMID: 16251415; PMCID: PMC1603774.
      Citations: 106     Fields:    Translation:AnimalsCells
    59. Hong J, Beeler J, Zhukovskaya NL, He W, Tang WJ, Rosner MR. Anthrax edema factor potency depends on mode of cell entry. Biochem Biophys Res Commun. 2005 Sep 30; 335(3):850-7. PMID: 16099427.
      Citations: 14     Fields:    Translation:HumansAnimalsCells
    60. Guo Q, Shen Y, Lee YS, Gibbs CS, Mrksich M, Tang WJ. Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin. EMBO J. 2005 Sep 21; 24(18):3190-201. PMID: 16138079; PMCID: PMC1224690.
      Citations: 69     Fields:    Translation:Cells
    61. Alappat EC, Feig C, Boyerinas B, Samuels M, Murmann AE, Thorburn A, Kidd VJ, Slaughter CA, Osborn SL, Winoto A, Tang WJ, Peter ME, Volkland J. Phosphorylation of FADD at serine 194 by CKIalpha regulates its nonapoptotic activities. Mol Cell. 2005 Aug 05; 19(3):321-32. PMID: 16061179.
      Citations: 58     Fields:    Translation:HumansAnimalsCells
    62. Quesnel-Hellmann A, Mathieu J, Montecucco C, Tang WJ, Vidal DR, Goossens PL, Tournier JN, Mock M. Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells. J Immunol. 2005 Apr 15; 174(8):4934-41. PMID: 15814721.
      Citations: 65     Fields:    Translation:AnimalsCells
    63. Shen Y, Zhukovskaya NL, Guo Q, Tang WJ, Florián J. Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor. EMBO J. 2005 Mar 09; 24(5):929-41. PMID: 15719022; PMCID: PMC554124.
      Citations: 67     Fields:    Translation:Cells
    64. Paccani SR, Tonello F, Ghittoni R, Natale M, Muraro L, D'Elios MM, Tang WJ, Montecucco C, Baldari CT. Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling. J Exp Med. 2005 Feb 07; 201(3):325-31. PMID: 15699068; PMCID: PMC2213032.
      Citations: 85     Fields:    Translation:HumansCells
    65. Beeler JA, Yan SZ, Bykov S, Murza A, Asher S, Tang WJ. A soluble C1b protein and its regulation of soluble type 7 adenylyl cyclase. Biochemistry. 2004 Dec 14; 43(49):15463-71. PMID: 15581358.
      Citations: 4     Fields:    Translation:HumansCells
    66. Lee YS, Bergson P, He WS, Mrksich M, Tang WJ. Discovery of a small molecule that inhibits the interaction of anthrax edema factor with its cellular activator, calmodulin. Chem Biol. 2004 Aug; 11(8):1139-46. PMID: 15324815.
      Citations: 18     Fields:    Translation:AnimalsCells
    67. Min DH, Tang WJ, Mrksich M. Chemical screening by mass spectrometry to identify inhibitors of anthrax lethal factor. Nat Biotechnol. 2004 Jun; 22(6):717-23. PMID: 15146199.
      Citations: 39     Fields:    Translation:HumansCells
    68. Guo Q, Shen Y, Zhukovskaya NL, Tang WJ, Florián J. Structural and kinetic analyses of the interaction of anthrax adenylyl cyclase toxin with reaction products cAMP and pyrophosphate. J Biol Chem. 2004 Jul 09; 279(28):29427-35. PMID: 15131111.
      Citations: 26     Fields:    Translation:Cells
    69. Shen Y, Guo Q, Zhukovskaya NL, Drum CL, Bohm A, Tang WJ. Structure of anthrax edema factor-calmodulin-adenosine 5'-(alpha,beta-methylene)-triphosphate complex reveals an alternative mode of ATP binding to the catalytic site. Biochem Biophys Res Commun. 2004 Apr 30; 317(2):309-14. PMID: 15063758.
      Citations: 13     Fields:    Translation:Cells
    70. Shen Y, Zhukovskaya NL, Zimmer MI, Soelaiman S, Bergson P, Wang CR, Gibbs CS, Tang WJ. Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection. Proc Natl Acad Sci U S A. 2004 Mar 02; 101(9):3242-7. PMID: 14978283; PMCID: PMC365774.
      Citations: 52     Fields:    Translation:AnimalsCells
    71. Papa S, Zazzeroni F, Bubici C, Jayawardena S, Alvarez K, Matsuda S, Nguyen DU, Pham CG, Nelsbach AH, Melis T, De Smaele E, Tang WJ, D'Adamio L, Franzoso G. Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2. Nat Cell Biol. 2004 Feb; 6(2):146-53. PMID: 14743220.
      Citations: 161     Fields:    Translation:HumansAnimalsCells
    72. Beeler JA, Tang WJ. Expression and purification of soluble adenylyl cyclase from Escherichia coli. Methods Mol Biol. 2004; 237:39-53. PMID: 14501037.
      Citations: 1     Fields:    Translation:Cells
    73. Ulmer TS, Soelaiman S, Li S, Klee CB, Tang WJ, Bax A. Calcium dependence of the interaction between calmodulin and anthrax edema factor. J Biol Chem. 2003 Aug 01; 278(31):29261-6. PMID: 12724328.
      Citations: 26     Fields:    Translation:Cells
    74. Soelaiman S, Wei BQ, Bergson P, Lee YS, Shen Y, Mrksich M, Shoichet BK, Tang WJ. Structure-based inhibitor discovery against adenylyl cyclase toxins from pathogenic bacteria that cause anthrax and whooping cough. J Biol Chem. 2003 Jul 11; 278(28):25990-7. PMID: 12676933.
      Citations: 38     Fields:    Translation:Cells
    75. Shen Y, Lee YS, Soelaiman S, Bergson P, Lu D, Chen A, Beckingham K, Grabarek Z, Mrksich M, Tang WJ. Physiological calcium concentrations regulate calmodulin binding and catalysis of adenylyl cyclase exotoxins. EMBO J. 2002 Dec 16; 21(24):6721-32. PMID: 12485993; PMCID: PMC139101.
      Citations: 43     Fields:    Translation:Cells
    76. Drum CL, Yan SZ, Bard J, Shen YQ, Lu D, Soelaiman S, Grabarek Z, Bohm A, Tang WJ. Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. Nature. 2002 Jan 24; 415(6870):396-402. PMID: 11807546.
      Citations: 159     Fields:    Translation:HumansAnimalsCells
    77. Yan SZ, Tang WJ. Expression of alpha subunit of Gs in Escherichia coli. Methods Enzymol. 2002; 344:171-5. PMID: 11771381.
      Citations: 6     Fields:    Translation:Cells
    78. Yan SZ, Tang WJ, Yan SZ, Tang WJ. Construction of soluble adenylyl cyclase from human membrane-bound type 7 adenylyl cyclase. Methods Enzymol. 2002; 345:231-41. PMID: 11665607.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    79. Drum CL, Shen Y, Rice PA, Bohm A, Tang WJ. Crystallization and preliminary X-ray study of the edema factor exotoxin adenylyl cyclase domain from Bacillus anthracis in the presence of its activator, calmodulin. Acta Crystallogr D Biol Crystallogr. 2001 Dec; 57(Pt 12):1881-4. PMID: 11717504.
      Citations: 11     Fields:    Translation:Cells
    80. Yan SZ, Beeler JA, Chen Y, Shelton RK, Tang WJ. The regulation of type 7 adenylyl cyclase by its C1b region and Escherichia coli peptidylprolyl isomerase, SlyD. J Biol Chem. 2001 Mar 16; 276(11):8500-6. PMID: 11113152.
      Citations: 16     Fields:    Translation:HumansCells
    81. Drum CL, Yan SZ, Sarac R, Mabuchi Y, Beckingham K, Bohm A, Grabarek Z, Tang WJ. An extended conformation of calmodulin induces interactions between the structural domains of adenylyl cyclase from Bacillus anthracis to promote catalysis. J Biol Chem. 2000 Nov 17; 275(46):36334-40. PMID: 10926933.
      Citations: 22     Fields:    Translation:Cells
    82. Hou P, Yan S, Tang W, Nelson DJ. The inwardly rectifying K(+) channel subunit GIRK1 rescues the GIRK2 weaver phenotype. J Neurosci. 1999 Oct 01; 19(19):8327-36. PMID: 10493734; PMCID: PMC6783034.
      Citations: 4     Fields:    Translation:AnimalsCells
    83. Tang WJ, Hurley JH. Catalytic mechanism and regulation of mammalian adenylyl cyclases. Mol Pharmacol. 1998 Aug; 54(2):231-40. PMID: 9687563.
      Citations: 46     Fields:    Translation:AnimalsCells
    84. Yan SZ, Huang ZH, Andrews RK, Tang WJ. Conversion of forskolin-insensitive to forskolin-sensitive (mouse-type IX) adenylyl cyclase. Mol Pharmacol. 1998 Feb; 53(2):182-7. PMID: 9463474.
      Citations: 17     Fields:    Translation:AnimalsCells
    85. Tang WJ, Yan S, Drum CL. Class III adenylyl cyclases: regulation and underlying mechanisms. Adv Second Messenger Phosphoprotein Res. 1998; 32:137-51. PMID: 9421589.
      Citations: 8     Fields:    Translation:HumansAnimalsCells
    86. Yan SZ, Huang ZH, Rao VD, Hurley JH, Tang WJ. Three discrete regions of mammalian adenylyl cyclase form a site for Gsalpha activation. J Biol Chem. 1997 Jul 25; 272(30):18849-54. PMID: 9228061.
      Citations: 5     Fields:    Translation:AnimalsCells
    87. Yan SZ, Huang ZH, Shaw RS, Tang WJ. The conserved asparagine and arginine are essential for catalysis of mammalian adenylyl cyclase. J Biol Chem. 1997 May 09; 272(19):12342-9. PMID: 9139678.
      Citations: 21     Fields:    Translation:AnimalsCells
    88. Guo W, Tang WJ, Bu X, Bermudez V, Martin M, Folk WR. AP1 enhances polyomavirus DNA replication by promoting T-antigen-mediated unwinding of DNA. J Virol. 1996 Aug; 70(8):4914-8. PMID: 8763994; PMCID: PMC190441.
      Citations: 14     Fields:    Translation:Cells
    89. Yan SZ, Hahn D, Huang ZH, Tang WJ. Two cytoplasmic domains of mammalian adenylyl cyclase form a Gs alpha- and forskolin-activated enzyme in vitro. J Biol Chem. 1996 May 03; 271(18):10941-5. PMID: 8631912.
      Citations: 20     Fields:    Translation:AnimalsCells
    90. Tang WJ, Stanzel M, Gilman AG. Truncation and alanine-scanning mutants of type I adenylyl cyclase. Biochemistry. 1995 Nov 07; 34(44):14563-72. PMID: 7578062.
      Citations: 29     Fields:    Translation:AnimalsCells
    91. Tang WJ, Gilman AG. Construction of a soluble adenylyl cyclase activated by Gs alpha and forskolin. Science. 1995 Jun 23; 268(5218):1769-72. PMID: 7792604.
      Citations: 37     Fields:    Translation:Cells
    92. Taussig R, Tang WJ, Hepler JR, Gilman AG. Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases. J Biol Chem. 1994 Feb 25; 269(8):6093-100. PMID: 8119955.
      Citations: 61     Fields:    Translation:AnimalsCells
    93. Taussig R, Tang WJ, Gilman AG. Expression and purification of recombinant adenylyl cyclases in Sf9 cells. Methods Enzymol. 1994; 238:95-108. PMID: 7799806.
      Citations: 4     Fields:    Translation:AnimalsCells
    94. Tang WJ, Gilman AG. Adenylyl cyclases. Cell. 1992 Sep 18; 70(6):869-72. PMID: 1525824.
      Citations: 87     Fields:    Translation:AnimalsCells
    95. Tang WJ, Mumby S, Gilman AG, Iñiguez-Lluhi JA. Regulation of mammalian adenylyl cyclases by G-protein alpha and beta gamma subunits. Cold Spring Harb Symp Quant Biol. 1992; 57:135-44. PMID: 1339652.
      Citations: 8     Fields:    Translation:HumansAnimalsCells
    96. Tang WJ, Gilman AG. Type-specific regulation of adenylyl cyclase by G protein beta gamma subunits. Science. 1991 Dec 06; 254(5037):1500-3. PMID: 1962211.
      Citations: 175     Fields:    Translation:AnimalsCells
    97. Tang WJ, Krupinski J, Gilman AG. Expression and characterization of calmodulin-activated (type I) adenylylcyclase. J Biol Chem. 1991 May 05; 266(13):8595-603. PMID: 2022671.
      Citations: 76     Fields:    Translation:HumansAnimalsCells
    98. Tang WJ, Folk WR. Constitutive expression of simian virus 40 large T antigen in monkey cells activates their capacity to support polyomavirus replication. J Virol. 1989 Dec; 63(12):5478-82. PMID: 2555568; PMCID: PMC251220.
      Citations: 5     Fields:    Translation:AnimalsCells
    99. Krupinski J, Coussen F, Bakalyar HA, Tang WJ, Feinstein PG, Orth K, Slaughter C, Reed RR, Gilman AG. Adenylyl cyclase amino acid sequence: possible channel- or transporter-like structure. Science. 1989 Jun 30; 244(4912):1558-64. PMID: 2472670.
      Citations: 115     Fields:    Translation:AnimalsCells
    100. Tang WJ, Folk WR. Asp-286----Asn-286 in polyomavirus large T antigen relaxes the specificity of binding to the polyomavirus origin. J Virol. 1989 Jan; 63(1):242-9. PMID: 2535730; PMCID: PMC247678.
      Citations: 9     Fields:    Translation:Cells
    101. Martin ME, Piette J, Yaniv M, Tang WJ, Folk WR. Activation of the polyomavirus enhancer by a murine activator protein 1 (AP1) homolog and two contiguous proteins. Proc Natl Acad Sci U S A. 1988 Aug; 85(16):5839-43. PMID: 2842750; PMCID: PMC281860.
      Citations: 78     Fields:    Translation:AnimalsCells
    102. Tang WJ, Berger SL, Triezenberg SJ, Folk WR. Nucleotides in the polyomavirus enhancer that control viral transcription and DNA replication. Mol Cell Biol. 1987 May; 7(5):1681-90. PMID: 3037332; PMCID: PMC365268.
      Citations: 37     Fields:    Translation:Cells
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