Wang, Hongyan

Research Interests:

Dr. Wang is a receipt of Singapore National Academy of Science Young Scientist Award (2008) and National Research Foundation (NRF) Research Fellowship (2009). Our group is interested in discovering the molecular mechanisms of neural stem cell self-renewal and differentiation. The choice of self-renewal versus differentiation is a fundamental issue in stem cell and cancer biology. Asymmetric cell division provides one common mechanism by which stem cell self-renewal and differentiation are balanced.
Recently, Drosophila melanogaster neural stem cells, larval brain neuroblasts, were emerged as an excellent model for study stem cell self-renewal and differentiation. Neuroblasts typically divide asymmetrically to generate a self-renewing neuroblast and a Ganglion Mother cell, which divides terminally to produce two differentiating neurons/glia. Perturbation of asymmetric division can often lead to tumor formation due to uncontrolled proliferation and aberrant differentiation. When transplanted into wild-type adult abdomen, mutant larval brain tissue from pins, mira, numb, or pros (mutants that are defective in asymmetric division of neuroblasts) can form malignant tumors that rapidly kill the host. Factors controlling self-renewal and differentiation are polarized during asymmetric division of neuroblasts. For example, tumor suppressors Brain Tumor (Brat), Prospero, and Numb are segregated to the differentiating daughter to inhibit self-renewal, whereas neuroblast proliferation factor atypical PKC (aPKC) is segregated to the self-renewing neuroblast during asymmetric division. We are focused on identifying brain tumor suppressors and the underlying mechanisms by which they prevent tumor formation in larval brains. Our work may ultimately contribute to better therapies for various types of cancers including human brain tumors.

Figure legend: mts299 (defective in the catalytic subunit of PP2A) mutant larval brains are highly enlarged and form supernumerary neural stem cells that are marked by Deadpan (Dpn).

Selected Publications:

Kirilly D, Wong JL, Lim KH, Wang Y, Zhang H, Wang C, Liao Q, Wang H, Hongyan Wang and Fengwei Yu. Intrinsic epigenetic factors cooperate with the steroid hormone ecdysone to govern dendrite pruning in Drosophila. Neuron. (in press).

Wang C, Li S, Januschke J, Rossi F, Izumi Y, Garcia-Alvarez G, Gwee SL, Soon SB, Sidhu HK, Yu F, Matsuzaki F, Gonzalez C, and Hongyan Wang. An Ana2/Ctp/Mud Complex Regulates Spindle Orientation in Drosophila Neuroblasts. (2011). Developmental Cell, 21, 520-33.

Chang KC, Garcia-Alvarez G, Somers G, Sousa-Nunes R, Rossi F, Lee YY, Soon SB, Gonzalez C, Chia W and Hongyan Wang. Interplay between the Transcription Factor Zif and aPKC Regulates Neuroblast Polarity and Self-renewal. (2010). Developmental Cell, 19, 778-85. (Press release by Development Cell, Duke University and Duke-NUS).

Kirilly D, Gu Y, Huang Y, Wu Z, Bashirullah A, Low BC, Kolodkin AL, Wang H and Yu F. A genetic pathway composed of Sox14 and Mical governs severing of dendrites during pruning. (2009). Nature Neuroscience 12, 1497-505. [“News and Views” in Nature Neuroscience 12,1479-80]

Wang H. (2009) Letter from the guest editor. Cell Adhesion & Migration Oct;3(4):395.

Wang C., Chang KC, Somers GW, Virshup D, Ang BT, Tang C, Yu F and Wang H. Protein Phosphatase 2A regulates self-renewal of Drosophila neural stem cells. (2009) Development 136, 2287-96. (Press released by Development, Duke University and Duke-NUS)

Chia W., Somers WG, Wang H. Drosophila neuroblast asymmetric divisions: Cell cycle regulators, asymmetric protein localization and tumourigenesis. The Journal of Cell Biology 182, 267-72 (2008)

Wang H, Ouyang Y, Somers GW, Chia W and Lu B. Polo inhibits neural progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon. Nature 449, 96-100 (2007)

Wang H, Somers GW, Bashirullah A, Heberlein U, Yu F and Chia W. Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Genes and Development, 20:3453-63 (2006). (Press released by Cold Spring Harbor Laboratory Press)

Wang H, Ng KH, Qian H, Siderovski DP, Chia W and Yu F. RIC-8 controls Drosophila neural progenitor asymmetric division by regulating heterotrimeric G proteins. Nature Cell Biology 7:1091-1098 (2005).  [“News and Views”in Nature Cell Biology 7: 1047-1049 (2005); “Research Highlight”in Nature Reviews Molecular Cell Biology 6, 905-905, 2005]

Yu F, Wang H, Qian HL, Kaushik R, Bownes M, Yang X, Chia W. Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions. Genes and Development 19:1341-1353 (2005).

Wang H and Chia W. Drosophila neural progenitor polarity and asymmetric division. Biology of the Cell 97: 63–74 (2005).