Research Interests

  • Obesity-induced metabolic changes
  • Body weight regulation
  • Identification and characterization of small molecular weight compounds with therapeutic potentials against metabolic syndrome

Research Summary

Obesity is a metabolic disease with increasing prevalence in modern society. It is also a risk factor to many health problems like diabetes, non-alcoholic liver steatosis, atherosclerosis and development of certain cancers. The causes of these disorders in obese subjects involve complex interactions between different regulatory systems and thus the underlying pathological mechanisms are still ambiguous. The major research interest of our laboratory is to study the disease mechanisms of obesity-induced metabolic changes at the molecular level. We are also interested in identifying new signaling pathways that control energy metabolism and body weight gain during obesity development. Using molecular, biochemical and genetic approaches, we aim to dissect the aberrant cellular signal transduction pathways in obese tissues, which will ultimately lead to the development of new therapeutic agents for obesity and its related diseases.

Current research projects include:

  • Studying the glucose and lipid metabolisms in obese muscle
  • Identification of novel signaling pathway that controls adipogenesis
  • Development and characterization of new anti-obesity drugs


Research articles:

  1. Zhang S., Chan C.B., Zhou W., Chen J., Appin C., Brat D.J. & Ye K. 2016 Fyn-phosphorylated PIKE-A Binds and Inhibits AMPK Signaling, Blocking its Tumor Suppressive Activity. Cell Death & Differentiation 23: 52-63.


  1. Gross C., Chang C., Kelly S.M., Bhattacharya A., McBride S.M.J., Danielson S.W., Jiang M.Q., Chan C.B., Ye K., Gibson J.R., Klann E., Jongens T.A., Moberg K.H., Huber K.M.& Bassell G.J. 2015 Increased expression of the PI3K enhancer PIKE mediates deficits in synaptic plasticity and behavior in Fragile X syndrome. Cell Reports 11: 727-736.
  2. Chan C.B., Tse M.C.L, Liu X., Zhang S., Schmidt R., Otten R., Liu L. & Ye K. 2015 Activation of Muscular TrkB by its Small Molecular Agonist 7,8-Dihydroxyflavone Sex-dependently Regulates Energy Metabolism in Diet-induced Obese Mice. Chemistry & Biology 22: 355-369. (Featured article)


  1. Liu X., Obianyo O., Chan C. B., Huang J., Xue S., Yang J., Zheng F., Goodman M. & Ye K. 2014 Biochemical and biophysical investigation of brain-derived neurotrophic factor mimetic 7,8-Dihydroxyflavone in binding and activation of TrkB receptor. Journal of Biological Chemistry 289: 27571-27584.
  2. Qiang G., Xue S., Yang J., Du G., Pang X., Li X., Goswami D., Griffin P., Ortlund E., Chan C.B.* & Ye K.* 2014 Identification of a small molecular insulin receptor agonist with potent anti-diabetic activity. Diabetes 63: 1394-1409. (*: Corresponding authors)
  3. Chan C.B., Liu X., Zhao L., Liu G., Lee C.W., Feng Y. and Ye K. 2014 PIKE is essential for oligodendroglia development and CNS myelination. Proceedings of the National Academy of Sciences USA 111: 1993-1998.
  4. Zhang Z., Liu X., Schroeder J., Chan C.B., Song M., Yu S.P., Weinshenker D. and Ye K. 2014 7,8-Dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology 39: 638-650.


  1. He K., Qi Q., Chan C.B., Xiao G., Liu X., Tucker-Burden C., Wang L., Mao H., Lu X., McDonald F.E., Luo H., Fan Q., Weiss W.A., Sun S., Brat D.J. and Ye K. 2013 Blockade of glioma proliferation through allosteric inhibition of JAK2. Science Signaling 6: ra55.
  2. Tse M.C.L., Liu X., Yang S., Ye K. and Chan C.B. 2013 Fyn regulates adipogenesis by promoting PIKE-A/STAT5a interaction. Molecular and Cellular Biology 33: 1797-1808.


  1. Hong Y., Chan C.B.*, Kwon I, Li X., Song M., Lee H., Liu X., Sompol P., Jin P., Lee H., Yu S.P. and Ye K.* 2012 SRPK2 phosphorylates tau and mediates the cognitive defects in Alzheimer’s disease. The Journal of Neuroscience 32: 17262-17272. (*Corresponding authors)
  2. Liu X., Chan C.B., Qi Q., Xiao G., Luo H.R., He X. and Ye K. 2012 Optimization of a small tropomyosin-related kinase B (TrkB) agonist 7,8-dihydroxyflavone active in mouse models of depression. Journal of Medicinal Chemistry 55: 8524-8537.
  3. Chan C.B., Chen Y., Liu X., Papale L., Escayg A., Mei L. and Ye K. 2012 Essential role of PIKE GTPases in neuronal protection against excitotoxic insults. Advances in Biological Regulation 52: 66-76.
  4. Qi Q, He K., Yoo M.H., Chan C.B., Liu X., Zhang Z., Olson J.J., Xiao G., Wang L., Mao H., Tao H., Ramalingam S.S., Sun S.Y., Mischel P.S. and Ye K. 2012 Acridine yellow G is an orally bioactive agent for blocking glioblastoma growth via dual inhibition of EGFR and PKC kinases. The Journal of Biological Chemistry 287: 6113-6127.


  1. He K., Chan C.B.*, Liu X., Jia Y., Luo H.R., France S.A., Liu Y., Wilson W.D., and Ye K*. 2011 Identification of a small molecular activator for insulin receptor with potent anti-diabetic effects in mice. The Journal of Biological Chemistry 286: 37379-37388. (* Corresponding authors)
  2. Chan C.B., Chen Y., Liu X., Tang X., Papale L., Escayg A., Mei L. and Ye K. 2011 PIKE-mediated PI 3-kinase activity is required for AMPA Receptor surface expression. The EMBO Journal 30: 4274-4286.
  3. Chan C.B., Liu X., He K., Jung D.Y., Kim J.K. and Ye K. 2011 PIKE-A association with hepatic insulin receptor is essential for its physiological functions. EMBO Reports 12: 847-854.
  4. Chan C.B., Liu X., Pradoldej S., Hao C., An J., Yepes M. and Ye K. 2011 Phosphoinositide 3-kinase enhancer regulates neuronal dendritogenesis and survival in neocortex. The Journal of Neuroscience 31: 8083-8092.


  1. Chan C.B., Liu X., Jung D.Y., Jun J.Y., Luo H.R., Kim J.K. and Ye K. 2010 Deficiency of PIKE protects mice from diet-induced obesity and insulin resistance. Diabetes 59: 883-893.
  2. Chan C.B., Liu X., Ensslin M.A., Dillehay D.L. and Ye K. 2010 Requirement of PIKE-A for STAT5 activation in mammary gland development. The EMBO Journal 29: 956-968.
  3. Liu X., Chan C.B., Pradoldej S., Jang S.W., Phun L.H., France S., Xiao G., Jia Y., Luo H.R. and Ye K. 2010 A synthetic 7,8-dihydroxyflavone derivative promotes neurogenesis and exhibit potent antidepressant effect. Journal of Medicinal Chemistry 53: 8274-8286.
  4. Gross C., Nakamoto M., Yao X., Chan C.B., Yim S.Y., Ye K., Warren S.T., and Bassell G. 2010 Excess PI3K subunit synthesis and activity as a novel therapeutic target in Fragile X Syndrome. The Journal of Neuroscience 30: 10624-10638.
  5. Jang S.W., Liu X., Chan C.B., France S., Sayeed I., Tang W., Lin X., Xiao G., Andero R., Chang Q., Ressler K.J. and Ye K. 2010 Deoxygedunin, a natural product with potent neurotrophic activity. PLoS ONE 5: e11528
  6. Oh S.M., Liu Z., Okada M., Jang S.W., Liu X., Chan C.B., Luo H. and Ye K. 2010 Ebp1 sumoylation, regulated by TLS/FUS E3 ligase, is required for its anti-proliferative activity. Oncogene 29:1017-1030.


  1. Chan C.B., Abe M., Hashimoto N., Hao C., Williams I.R., Liu X., Nakao S., Yamamoto Z, Zheng C., Henter J., Meeths M., Nordenskjold M., Li S., Hara-Nishimura I., Asano M., and Ye K. 2009 Mice lacking asparagine endopeptidase (AEP) develop disorders resembling hemophagocytic syndrome. Proceedings of the National Academy of Sciences USA 106:468-473
  2. Chan C.B., Liu X., Jang S.W. Hsu S.I.H. and Ye K. 2009 NGF inhibits human leukemia proliferation by downregulating cyclin A1 expression through promoting acinus/CtBP2 association. Oncogene 28: 3825-3836.
  3. Jang S.W., Liu X., Chan C.B., Weinshenker D., Hall R.A., Xiao G. and Ye K. 2009 Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chemistry & Biology 16: 644-656.
  4. Lau P.N., Chow K.B.S., Chan C.B., Cheng C.H.K. and Wise H. 2009 The constitutive activity of the ghrelin receptor attenuates apoptosis via a protein kinase C-dependent pathway. Molecular and Cellular Endocrinology 299: 232-239.


  1. Jiao B., Yeung E.K.C., Chan C.B. and Cheng C.H.K. 2008 Establishment of a transgenic yeast screening system for estrogenicity and identification of the anti-estrogenic activity of malachite green. Journal of Cellular Biochemistry 105:1399-1409.
  2. Tang X., Jang S.W., Okada M., Chan C.B., Feng Y, Liu Y., Luo S.W., Hong Y., Rama N., Xiong, W.C. and Ye K. 2008 Netrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B. Nature Cell Biology 10:698-706.


  1. Chan C.B., Liu X., Tang X., Fu H. and Ye K. 2007 Akt phosphorylation of zyxin mediates its interaction with acinus-S and prevents acinus-triggered chromatin condensation. Cell Death & Differentiation 14: 1688-1699.
  2. Chan C.B. Tang W.K., Cheng C.H.K and Fong W.P. 2007 Cloning of the black seabream (Acanthopagrus schlegeli) antiquitin gene and functional characterization of its promoter region. Molecular and Cellular Biochemistry 297: 151-160.
  3. Wang X., Yue P., Chan C.B., Ye K., Ueda T., Watanabe-Fukunaga R., Fukunaga R., Fu H., Khuri F.R. and Sun S.Y. 2007 Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3 kinase-dependent and Mnk-mediated eIF4E phosphorylation. Molecular and Cellular Biology 27:7405-7413.
  4. Huang X., Jiao B., Fung C.K., Ho W.K.K., Zhang Y., Chan C.B., Lin H., Wang D. and Cheng C.H.K. 2007 The presence of two distinct prolactin receptors in seabream with different tissue distribution patterns, signal transduction pathways and regulation of gene expression by steroid hormones. Journal of Endocrinology 194: 373-392.
  5. Leung P.K., Chow K.B.S., Lau P.N., Chu K.M., Chan C.B., Cheng C.H.K. and Wise H 2007 The truncated ghrelin receptor peptide (GHSR-1b) acts as a dominant-negative mutant of the ghrelin receptor. Cellular Signaling 19: 1011-1022.
  6. Chu K.M., Chow K.B.S., Leung P.K., Lau P.N., Chan C.B., Cheng C.H.K. and Wise H. 2007 Over-expression of the truncated ghrelin receptor polypeptide attenuates the constitutive activation of phosphatidylinositol-specific phospholipase C by ghrelin receptors but has no effect on ghrelin-stimulated extracellular signal-regulated kinase 1/2 activity. International Journal of Biochemistry and Cell Biology 39: 752-764.


  1. Yeung C.M., Chan C.B., Woo N.Y.S. and Cheng C.H.K. 2006 The seabream ghrelin: cDNA cloning, genomic organization and promoter studies. Journal of Endocrinology 189:365-379.
  2. Jiao B., Huang X., Chan C.B., Zhang L., Wang D. and Cheng C.H.K. 2006 The co-existence of two growth hormone receptors in teleost fish and their differential signal transduction, tissue distribution and hormonal regulation of expression in seabream. Journal of Molecular Endocrinology 36:23-40.


  1. Tang W.K., Chan C.B., Cheng C.H.K. and Fong W.P. 2005 Seabream antiquitin: molecular cloning, tissue distribution, subcellular localization and functional expression. FEBS Letters 579:3759-3764.


  1. Chan C.B., Fung W., Tse M.C.L., Fung C.K. and Cheng C.H.K. 2004 Stimulation of growth hormone secretion from seabream pituitary cells in primary culture by growth hormone secretagogues is independent of growth hormone transcription. Comparative Biochemistry and Physiology Part C Toxicology and Pharmacology 39:77-85.
  2. Chan C.B., Leung C.P.K., Wise H. and Cheng C.H.K. 2004 Signal transduction mechanism of the seabream growth hormone secretagogue receptor. FEBS Letters 577:147-153.
  3. Chan C.B. and Cheng C.H.K. 2004 Identification and functional characterization of two alternatively spliced growth hormone secretagogue receptor transcripts from the pituitary of black seabream Acanthopagrus schlegeli. Molecular and Cellular Endocrinology 214:81-95.
  4. Yeung C.M., Chan C.B. and Cheng C.H.K. 2004 Isolation and characterization of the 5’-flanking region of the growth hormone secretagogue receptor gene from black seabream Acanthopagrus schlegeli. Molecular and Cellular Endocrinology 223:5-15.


  1. Tse D.L.Y., Tse M.C.L., Chan C.B., Deng L., Zhang W.M., Hiu H.R. and Cheng C.H.K. 2003 Seabream growth hormone receptor: molecular cloning and functional studies of the full-length cDNA, and tissue distribution of two alternatively spliced forms. Biochimica et Biophysica Acta 1625:64-76.


  1. Tse D.L.Y., Chow B.K.C., Chan C.B., Lee L.T.O. and Cheng C.H.K. 2000 Molecular cloning and expression studies of a prolactin receptor in goldfish (Carassius auratus). Life Sciences 66: 593-605.

Invited reviews and book chapters:

  1. Liu C., Chan C.B. and Ye K. 2016 7,8-Dihydroxyflavone, a small molecular TrkB Agonist, useful for treating various BDNF-implicated human disorders. Translational Neurodegeneration 5: 2-10.
  2. Chan C.B.* and Ye K. 2013 Serine-arginine protein kinases: new players in neurodegenerative diseases? Reviews in the Neurosciences 24: 401-413. (*: Corresponding author)
  3. Chan C.B. and Ye K. 2012 SRPK2 activity and Alzheimer’s dementia. Cognitive Sciences 7: 1-23.
  4. Chan C.B.* and Ye K. 2012 PIKE in the brain: Is it simply a phosphoinositide 3-kinase/Akt enhancer? Reviews in the Neurosciences 23: 153-161. (*: Corresponding author)
  5. Chan C.B. and Ye K. 2011 What we have learnt about PIKE from the knockout mice. International Journal of Biochemistry and Molecular Biology 2: 228-239.
  6. Chan C.B. and Ye K. 2010 Nuclear Akt: an important kinase in an inconspicuous compartment. Trends in Cell & Molecular Biology 5: 35-48.
  7. Chan C.B. and Ye. K. 2010 Multiple functions of phosphoinositide-3 kinase enhancer. TheScientificWorldJOURNAL 10:613-623.
  8. Chan C.B. and Ye K. 2007 CENTG1 (Centaurin, gamma1). Atlas of Genetics and Cytogenetics in Oncology and Haematology 11: 52-54.
  9. Chan C.B. and Ye K. 2007 PIKE GTPase are phosphoinositide-3-kinase enhancers, suppressing programmed cell death. Journal of Cellular and Molecular Medicine 11:39-53.
  10. Yeung C.M., Chan C.B. and Cheng C.H.K. 2006 Cells of the anterior pituitary. International Journal of Biochemistry and Cell Biology 38: 1441-1449.
  11. Chan C.B., Tse M.C.L. and Cheng C.H.K. 2005 Regulation and mechanism of growth hormone and insulin-like growth factor-I biosynthesis and secretion. p3-19 In “The somatotrophic axis in brain function” Nyberg F. eds. Elsevier Academic Press, San Diego, CA, USA.