Hong Ye, Ph.D.

Education:

B.S. Cell Biology, Xiamen University, China, 1991
Ph.D.  Biophysics, Keele University, United Kingdom, 1998
Postdoctoral Fellow: Biochemistry, Weill Medical College of Cornell University, 1998-2003

Curriculum Vitae

Current Positions:

Associate Professor, Brown Cancer Center, University of Louisville
Associate Professor, Department of Medicine, University of Louisville
Associate member, Department of Pharmacology, University of Louisville
Associate member, Department of Chemistry, University of Louisville

Contact Information:

CTR Building, room 204
University of Louisville
505 S. Hancock St
Louisville, KY 40202
Phone: 502-852-4047
Fax 502-852-7979

Email: hong.ye@louisville.edu

Research Description:

The Ye laboratory focuses on two aspects that have fundamental impact to human health. The first research direction is to study the structure and function of Smc5/6 complex, a group of proteins responsible for maintaining genome stability and DNA damage repair functions. The second direction is to develop the therapeutic compounds from medicinal nature herbs which have ability to inhibit inflammation. Besides our research focuses, we also collaborate individual labs that have needs of structural information to assist their research progress.

The specific research focuses are described here:

    1. Structural and functional studies of Smc5/6 complex on DNA damage and repair.

      The DNA replication and recombination process is a fundamental process for all species, its failure not only leads to tumorigenesis and various developmental diseases, but can directly lead to death of the individual. Smc5/6, an evolutionarily conserved protein complex, plays a crucial role in the repair of damaged DNA during replication and recombination. To accomplish this, we primarily use X-ray crystallography, which is a powerful tool that allows visualization of molecular details at the atomic level. In combination with the other biophysical and biochemical methods such as isothermal titration calorimetry (ITC), analytic ultracentrifugation (AUC), electron microscopy (EM), atomic force microscopy (AFM), and enzymatic assay approaches, we have been able to elucidate the protein-protein interactions and regulations involved in chromosome maintenance and DNA repair processes. The goal of this research is to understand the detailed mechanisms of these processes.

        2. Drug discovery for anti-inflammation related diseases from medicinal nature herbs.

        Inflammation is the pervasive phenomenon that recognizes and repairs disrupted tissues coordinated by cytokines in immune system. The inflammatory cascade is a very complex network, and abnormal inflammation relates or leads to various diseases including rheumatoid arthritis, multiple sclerosis, diabetes, and cancer. Finding a drug which is able to regulate inflammation is the key to alleviating these diseases. Various medicinal herbs have been used to treat inflammation related diseases as documented across human history. Our lab has selected a few medicinal herbs. A combined extract from these herbs has been shown to have a compelling ability to reduce inflammation in patients. Further experiments have confirmed that the herbal extract combination is able to reduce inflammation in a mouse model. In addition, we have established that the extract is able to reduce the inflammatory response biomarker TNFα in macrophage cells. The ultimate goal of this research is to identify the minimum combination of compounds with maximum effect for regulating inflammation, and furthermore, to find the mechanism by which these compounds are able to reduce inflammation.

        Literature Cited (15 Max.):

        1. Ye H, Park YC, Kreishman M, Kieff E, Wu H. 1999. The structural basis for the recognition of diverse receptor sequences by TRAF2. Mol Cell 4: 321-30
        2. Park YC, Ye H, Hsia C, Segal D, Rich RL, et al. 2000. A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction. Cell 101: 777-87
        3. Ye H, Wu H. 2000. Thermodynamic characterization of the interaction between TRAF2 and tumor necrosis factor receptor peptides by isothermal titration calorimetry. Proc Natl Acad Sci U S A 97: 8961-6
        4. Ye H, Arron JR, Lamothe B, Cirilli M, Kobayashi T, et al. 2002. Distinct molecular mechanism for initiating TRAF6 signalling. Nature418: 443-7
        5. Ye H, Cande C, Stephanou NC, Jiang S, Gurbuxani S, et al. 2002. DNA binding is required for the apoptogenic action of apoptosis inducing factor. Nat Struct Biol9: 680-4
        6. Ye H, Cirilli M, Wu H. 2002. The use of construct variation and diffraction data analysis in the crystallization of the TRAF domain of human tumor necrosis factor receptor associated factor 6. Acta Crystallogr D Biol Crystallogr 58: 1886-8
        7. Ye H, Chen T-C, Xiaohui Xu M, Pennycooke M, Wu H, Steegborn C. 2004. Crystal structure of the putative adapter protein MTH1859. J. Stru. Biol. 148: 251-256
        8. Duan X., Trent J.O., Ye H. 2009. Targeting the SUMO E2 conjugating enzyme Ubc9 interaction for anti-cancer drug design. Anticancer Agents Med. Chem.9:51-4.
        9. Duan X., Yang Y., Chen Y.H., Arenz J., Rangi G.K., Zhao X., Ye H. 2009. Architecture of the Smc5/6 Complex of Saccharomyces cerevisiae Reveals a Unique Interaction between the Nse5-6 Subcomplex and the Hinge Regions of Smc5 and Smc6.J. Biol. Chem. 284: 8507-15
        10. Duan X., Ye H. 2009. Purification, crystallization, and preliminary X-ray crystallographic studies of the complex between Smc5 and SUMO E3 ligase Mms21.Acta Crystallogr Sect F Struct Biol Cryst Commun. 65:849-52.
        11. Duan X., Sarangi P., Liu X., Rangi G.K., Zhao X., Ye H. 2009. Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex. Mol. Cell. 35(5):657-68
        12. Chen Y.H., Choi K., Szakal B., Arenz J., Duan X., Ye H., Branzei D., Zhao X. 2009. Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc. Natl. Acad. Sci. U. S. A. 106: 21252-7
        13. Duan X, Holmes WB, Ye H. 2011. Interaction mapping between Saccharomyces cerevisiae Smc5 and SUMO E3 ligase Mms21.Biochemistry. 50(46):10182-8.
        14. Vaishnav RA, Liu R, Chapman J, Roberts AM, Ye H, Rebolledo-Mendez JD, Tabira T, Fitzpatrick AH, Achiron A, Running MP, Friedland RP. 2013. Aquaporin 4 molecular mimicry and implications for neuromyelitis optica.J Neuroimmunol. 260: 92-8.
        15. Ding C, Ma Y, Chen X, Liu M, Cai Y, Hu X, Xiang D, Nath S, Zhang HG, Ye H, Powell D, Yan J. 2013. Integrin CD11b negatively regulates BCR signalling to maintain autoreactive B cell tolerance.Nat Commun. 4: 2813.

        PubMed Information