616.234.5000

Yuanzheng He, Ph.D.

Xu Laboratory
Yuanzheng He, Ph.D.
Senior Research Scientist, Xu Laboratory
616.234.5727

Biography

After graduating from the Chinese Academy of Sciences’ Shanghai Institute of Biochemistry in 2000, Dr. He worked as a postdoctoral fellow in Dr. Stoney Simons’s lab at the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health in Maryland. While there, he studied the mechanism of steroid hormone receptor-regulated gene expression, specifically the glucocorticoid receptor. In 2008, Dr. He was recruited to Van Andel Research Institute to work on drug discovery for the glucocorticoid receptor and the structural relationship between ligand recognition and receptor function. He is a senior research scientist in the laboratory of Dr. H. Eric Xu.

 

 

 

 

 

Research

Steroid hormone receptors play pivotal roles in regulating almost all essential physiology of the human body and are involved in a multitude of diseases including cancer, metabolic syndromes and immune disorders. Dr. He’s research focuses on the structural relationship between ligand recognition and receptor function, emphasizing specific conformations induced by particular ligands and related drug design. Currently, his main focus is on the mechanism of dissociated glucocorticoids, the design and development of the next generation of glucocorticoids, and the cross-talk between lysosomal pathways and glucocorticoid signaling.

Specific projects include:

  • Determining the mechanism of dissociated glucocorticoids, which retain only the beneficial anti-inflammation activity of glucocorticoids but not the unwanted side effects
  • Designing and developing next-generation glucocorticoids that have greatly reduced side effects and are more effective than current glucocorticoid drugs
  • Determining the mechanism of lysosome-regulated glucocorticoid signaling

Selected publications

To view a list of selected publications click below.

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Kang Y, Zhou XE Gao X, He Y, Liu W, Ishchenko A, Barty A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Ke J, Tan MHE, Zhang C, Moeller A, West GM, Pascal B, Eps NV, Caro1 LN, Vishnivetskiy SA, Lee RJ, Suino-Powell KM, Gu X, Pal K, Ma J, Zhi XY, Boutet S, Williams GJ, Messerschmidt M, Gati C, Zatsepin NA, Wang D, James D, Basu S, Roy-Chowdhury S, Conrad C, Coe J, Liu H, Lisova S, Kupitz C, Grotjohann I, Fromme R, Jiang Y, Tan M, Yang H, Li J, Wang M, Zheng Z, Li D, Howe N,  Zhao Y, Standfuss J, Diederichs K, Dong Y, Potter CS, Carragher B, Caffrey M, Jiang H, Chapman HN, Spence JCH, Fromme P, Weierstall U, Ernst OP, Katritch V, Gurevich VV, Griffin PR, Hubbell WL, Stevens RC, Cherezov V, Melcher K, Xu HE 2015. Crystal structure of rhodopsin bound to arrestin determined by femtosecond X-ray laser. Nature 523(7562)561–567            Article
*Featured in Nature News & Views

Zhi X, Zhou XE, He Y, Searose-Xu K, Zhang CL, Tsai CC, Melcher K. Xu HE. 2015. Structural basis for corepressor assembly by the orphan nuclear receptor TLX. Genes Dev 29(4)440–450           PubMed

He Y, Yi W, Suino-Powell K, Zhou XE, Tolbert WD, Tang X, Yang J, Yang H, Shi J, Hou L,Jiang H, Melcher K, Xu HE. 2014. Structures and mechanisms for the design of highly potent glucocorticoids. Cell Res 24(6):713 –726           PubMed

Jiang L, Liu X, Xiong G, Liu H, Chen F, Wang L, Meng X, Liu G, Yu H, Yuan Y, Yi W, Zhao L, Ma H, He Y, Wu Z, Melcher K, Qian Q, Xu HE, Wang Y, Li J. 2013. DWARF 53 acts as a repressor of stringolactone signalling in rice. Nature 504(7480): 401–405.        PubMed

Lee GS, He Y, Dougherty EJ, Jimenez-Movilla M, Avella M, Grullon S, Sharlin DS, Guo C, Blackford Jr JA, Awasthi S, Zhang Z, Armstrong SP, London EC, Chen W, Dean J, Simons Jr SS. 2013. Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility. J Biol Chem 288: 15167–15180.         PubMed

Zhao LH, Zhou XE, Wu ZS, Yi W, Xu Y, Li S, Xu TH, Liu Y, Chen RZ, Kovach A, Kang Y, Hou L, He Y, Xie C, Song W, Zhong D, Xu Y, Wang Y, Li J, Zhang C, Melcher K, Xu HE. 2013. Crystal structures of two phytohormone signal-transducing α/β hydrolases: karrikin-signaling KAI2 and stringolactone-signaling DWARF14. Cell Res 23(3): 436–439.          Article

Zhi X, Zhou XE, He Y, Zechner C, Suino-Powell KM, Kliewer SA, Melcher K, Mangelsdorf DJ, Xu HE. 2014. Structural insights into gene repression by the orphan nuclear receptor SHP. Proc Natl Acad Sci U S A 111(2): 839–844.          PubMed

Soon FF, Ng LM, Zhou XE, West GM, Kovach A, Tan MHE, Suino-Powell KM, He Y, Xu Y, Chalmers MJ, Joseph S. Brunzelle, Huiming Zhang, Huaiyu Yang, Hualiang Jiang, Jun Li, Eu-Leong Yong, Sean Cutler, Jian-Kang Zhu, Patrick R. Griffin, Karsten Melcher, and H. Eric Xu. 2012. Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases. Science 335(6064): 85–88.          PubMed

Ai J, Tang Q, Wu Y, Xu Y, Feng T, Zhou R, Chen Y, Gao X, Zhu Q, Yue X, Pan Q, Xu S, Li J, Huang M, Daugherty-Holtrop J, He Y, Xu HE, Fan J, Ding J, Geng M. 2011. The role of polymeric immunoglobulin receptor in inflammation-induced tumor metastasis of human hepatocellular carcinoma. J Natl Cancer Inst 103(22): 1696–1712.          PubMed

Guo Z, He Y, Wang S, Zhang A, Zhao P, Gao C, Cao B. 2011. Various effects of hepatoma-derived growth factor on cell growth, migration and invasion of breast cancer and prostate cancer cells. Oncol Rep 26(2): 511–517.          PubMed

He Y, Xu Y, Zhang C, Gao X, Dykema KJ, Martin KR, Ke J, Hudson EA, Khoo SK, Resau JH, Alberts AS, MacKeigan JP, Furge KA, Xu HE. 2011. Identification of a lysosomal pathway that modulates glucocorticoid signaling and the inflammatory response. Sci Signal 4(180): ra44.          PubMed

He Y, Blackford Jr JA, Kohn EC, Simons Jr SS. 2010. STAMP alters the growth of transformed and ovarian cancer cells. BMC Cancer 10(1):128.          PubMed

Zhou XE, Suino-Powell KM, Li J, He Y, MacKeigan JP, Melcher K, Yong EL, Xu HE. 2010. Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor. J Biol Chem 285(12): 9161–9171.         PubMed

Szapary D, Song LN, He Y, Simons Jr SS. 2008. Differential modulation of glucocorticoid and progesterone receptor transactivation. Mol Cell Endo 283: 114–126.         PubMed

He Y, Simons Jr SS. 2007. STAMP: a novel predicted factor assisting TIF2 actions in glucocorticoid receptor-mediated induction and repressionMol Cell Biol 27(4): 1467–1485.                       

Chen J, He Y, Simons Jr SS. 2004. Structure/activity relationships for GMEB-2: the second member of the glucocorticoid modulatory element-binding complex. Biochemistry 43(1): 245–255.         PubMed

He Y, Szapary D, Simons Jr SS. 2002. Modulation of induction properties of glucocorticoid receptor-agonist and -antagonist complexes by coactivators involves binding to receptors but is independent of ability of coactivators to augment transactivation. J Biol Chem 277(51): 49256–49266.