We focus on uncovering the epigenetic factors that promote progenitor cell differentiation into neuroendocrine cells. As a model, we study the mouse olfactory placode, which is the primary birthplace of gonadotropin-releasing hormone (GnRH) neurons. Following their emergence, GnRH neurons migrate to the preoptic and hypothalamus region to control puberty, fertility and reproduction. Deficits in GnRH neuron development and function are the hallmarks of a neuroendocrine disorder called Kallmann syndrome. Patients do not enter pubertal development, and are hence infertile. The long-term goal is to discover knowledge that can be used to develop precision therapeutics that prevent the onset or mitigate the clinical symptoms related to neuroendocrine diseases.
We use various molecular and cellular techniques, such as chromatin-immunoprecipitation, MeDIP, DNA sequencing, cell tissue cultures, embryonic mouse tissue explants, and high resolution imaging for these studies. Our data confirmed the hypothesis that embryonic FGF8 transcription depends on the interaction of epigenetic enzymes with DNA and histones. The main outcome is a better understanding of the epigenetic molecular mechanisms needed to control embryonic brain gene programs that facilitate normal and healthy brain function.
Kent State undergraduates who are interested in developmental neuroscience, and want to learn research techniques, such as cell culture, embryonic brain tissue explants, DNA/RNA isolation, quantitative PCR, protein analysis and immunocytochemistry should contact Dr. Chung (email@example.com) to set up an appointment. Please include in the email a short description of your interests.
Linscott ML, Chung WCJ (2020) Epigenomic control of gonadotropin-releasing hormone neuron development and hypogonadotropic hypogonadism. Journal Neuroendocrinology.
Jain S. Watts CA, Chung WCJ, Welshhans K (2020). Neurodevelopmental wiring deficits in the Ts65Dn mouse model of Down syndrome. Neuroscience Letters. 714: 134569.
Handa RJ, Chung WCJ (2019) Gender and stress. In: Handbook of Stress: Physiology, Biochemistry and Pathology, Vol 3. (Fink G Ed). San Diego: Academic Press: 116 - 176.
Kim CK, Torcaso A, Asimes AD, Chung WCJ, Pak TR (2018) Structural and functional characteristics of estrogen receptor beta (ERβ) splice variants: implications for the aging brain. Journal of Neuroendocrinology. 30:
Stewart CE, Corella KM, Samberg BD, Jones PT, Linscott ML, Chung WCJ (2016) Perinatal midline astrocyte development is impaired in fibroblast growth factor 8 hypomorphic mice. Brain Research. 1646: 287.
Linscott ML, Chung WCJ (2016) Fibroblast growth factor 8 expression in GT1-7 GnRH-secreting neurons is androgen-independent, but can be upregulated by the inhibition of DNA methyltransferases. Frontiers Cell and Developmental Biology. 4: 34.
Rodriguez KM, Stevenson EL, Stewart CE, Linscott ML, Chung WCJ (2015). Fibroblast growth factor 8 regulates postnatal development of paraventricular nucleus neuroendocrine cells. Behavioral Brain Functions. 11: 34.
Stevenson EL, Corella KM, Chung WCJ (2013) Ontogenesis of gonadotropin-releasing hormone neurons: a model for hypothalamic neuroendocrine cell development. Front Endocrinol. 4: 89.
Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung WCJ, et al (2013) Genetic screening of the FGF8 synexpression group identifies rare sequence variants in FGF17, IL17RD, DUSP6, SPRY4 and FLRT3 in patients with Congenital Hypogonadotropic Hypogonadism. American Journal of Human Genetics. 92: 725.
Rao YS, Mott NM, Wang Y, Chung WCJ, Pak TR (2013) A subset of miRNAs are differentially regulated by estrogen in the aging brain. Endocrinology. 154: 2795.
Chung WCJ, Auger AP (2013). Gender differences neurodevelopment and epigenetics. Pflugers Archiv. 465: 573.
Tsai TS, Brooks LR, Rochester JR, Kavanaugh SI, Chung WCJ (2011) Fibroblast growth factor signaling in the developing neuroendocrine hypothalamus. Frontiers of Neuroendocrinology.32: 95.
Chung WCJ, Matthews TA, Tata BK, Tsai PS (2010) Compound deficiencies in multiple FGF signaling components differentially impact the murine GnRH system. J Neuroendocrinology. 22: 944.
Chung WCJ, Moyle SS, Tsai PS (2008) Fibroblast growth factor 8 signaling through FGF receptor 1 is required for gonadotropin-releasing hormone neuronal development in mice. Endocrinology. 149: 4997.
Falardeau J, Chung WCJ, Beenken A, Plummer L, Sidis Y, Raivio T, Dwyer A, Na S, Hall J, Huot C, Alois N, Quinton R, Cole LW, Hughes V, Mohammadi M, Tsai PS, Pitteloud N (2008). Decreased FGF8 signaling causes GnRH deficiency in human and mice. J Clin Invest. 118: 2822.
Chung WCJ, Pak TR, Suzuki S, Pouliot WA, Andersen ME, Handa RJ (2007). Detection and localization of an estrogen receptor beta splice variant protein (ERbeta2) in the adult female rat forebrain and midbrain regions. J Comp Neurol.20: 249.
Pak TR, Chung WCJ, Hinds LR, Handa RJ (2007) Estrogen receptor-beta mediates DHT-induced stimulation of the arginine vasopressin promoter in neuronal cells. Endocrinology. 148:3371.
Pak TR, Chung WCJ, Roberts JL, Handa RJ (2006) Ligand-independent effects of estrogen receptor beta on mouse gonadotropin releasing hormone (GnRH) promoter activity. Endocrinology 147: 1924.
Chung WCJ, De Vries GJ, Swaab DF (2002) Sexual differentiation in the bed nucleus of the stria terminalis of the human extends into adulthood. J Neurosci 22: 1027.
Chung WCJ, Swaab DF, De Vries GJ (2000) Apoptosis during postnatal sexual differentiation of the bed nucleus of the stria terminalis in the rat brain. J Neurobiology 43: 234.
2003. PhD. Neurobiology. Netherlands Institute for Neuroscience, Department of Medicine, University of Amsterdam, The Netherlands
The Society for Neuroscience (www.sfn.org), The Endocrine Society (www.endo-society.org)