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The group has a rich history in basic science with publications in high impact journal such as Nature, Science, PNAS and EMBO in the fields of nuclear receptor biology. In 2013, one of our graduate students, Dr C. Chen in collaboration with Dr Eric Xu, a crystallographer from USA has solved the crystal structure of the folate receptor (Chen et al, Nature. 2013 22;500:486-9). These structures pave the way to develop drugs that will address diseases of due to folate metabolism for fetal neural tube defects to ovarian cancer.

Starting with the screening of phyto-extracts from Traditional Chinese Medicines, the group have moved on to the isolation, characterization, and patenting of novel compounds that activate AR, ER, PPAR and progesterone receptor signaling pathways. These compounds and their parent extracts have shown much potential for utility in menopause, bone health, metabolic disease, breast and prostate cancers.

This effort has resulted in 5 patent applications, three of which have been granted and commercialized. Based on our patent, NUS Industry Liaison Office officially signed a Research Collaboration Agreement with Schwabe pharmaceuticals GmbH & Co. KG, of Germany to develop pharmaceutical products from plants of genus Epimedium. We have received funding which has been used to complete the necessary pre-clinical pharmacokinetic and pharmacodynamic studies in animal models to meet regulatory requirements necessary for planned human trials.

Achievement of these planned Phase I/II human studies will result in pharmaceutical-quality botanical compounds for Singaporeans. Today, working alongside our German collaborator, Schwabe, and local manufacturer, we have obtained, and encapsulated GMP-quality Epimedium extract, which is currently listed as a Chinese Proprietary Medicine in Singapore for human consumption.

 

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Some publications representing our work

  • 1. Sun F, Zhang ZW, Tan EM, Lim ZL, Li Y, Wang XC, Chua SE, Li J, Cheung E, Yong EL. Icaritin suppresses development of neuroendocrine differentiation of prostate cancer through inhibition of IL-6/STAT3 and Aurora kinase A pathways in TRAMP mice. Carcinogenesis. 2016 Apr 19. pii: bgw044.
  • 2. Sun F, Indran IR, Zhang ZW, Tan MH, Li Y, Lim ZL, Hua R, Yang C, Soon FF, Li J, Xu HE, Cheung E, Yong EL. A novel prostate cancer therapeutic strategy using icaritin-activated arylhydrocarbon-receptor to co-target androgen receptor and its splice variants. Carcinogenesis. 2015 Jul;36(7):757-68.
  • 3. Indran IR, Liang RL, Min TE, Yong EL. Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health. Pharmacol Ther. 2016 Jan 25. pii: S0163-7258(16)00016-4.
  • 4. Tiong CT, Chen C, Zhang SJ, Li J, Soshilov A, Denison MS, Lee LS, Tam VH, Wong SP, Xu HE, Yong EL. A novel prenylflavone restricts breast cancer cell growth through AhR-mediated destabilization of ERα protein. Carcinogenesis. 2012 May;33(5):1089-97.
  • 5. Lee BH, Indran IR, Tan HM, Li Y, Zhang Z, Li J, Yong EL. A dietary medium-chain fatty acid, decanoic acid, inhibits recruitment of Nur77 to the HSD3B2 promoter in vitro, and reverses endocrine and metabolic abnormalities in a rat model of polycystic ovary syndrome. Endocrinology. 2016 Jan;157(1):382-94.
  • 6. Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS, Li J, Yong EL, Xu HE, Melcher K. Structural basis for molecular recognition of folic acid by folate receptors. Nature. 2013 Aug 22;500(7463):486-9.
  • 7. Molecular mimicry regulates ABA signaling by SnRK2 kinases and PP2C phosphatases. Soon FF, Ng LM, Zhou XE, West GM, Kovach A, Tan MH, Suino-Powell KM, He Y, Xu Y, Chalmers MJ, Brunzelle JS, Zhang H, Yang H, Jiang H, Li J, Yong EL, Cutler S, Zhu JK, Griffin PR, Melcher K, Xu HE.Science. 2012 Jan 6;335(6064):85-8.

 

Other Key Research Areas