B.Sc. (Bachelor of Science) Ph.D. (Doctor of Philosophy)

Molecular and Development Genetics Molecular Biology and Disease Cell Signalling and Structure

During organogenesis, cells face two major challenges. First, progenitor cells need to maintain a balance between self-renewal and differentiation to ensure the generation of the correct number of cell types. Second, differentiated cells need to maintain appropriate organization to confer organ functionality. Many human birth defects are due to failure in cellular differentiation, and many human diseases are caused by defects in organ maintenance. My lab is interested in understanding the molecular and cellular mechanisms that regulate cell differentiation and tissue maintenance. We use zebrafish as a model system, because molecular and genetic analyses can be combined with high-resolution in vivo imaging and large-scale small molecule screens. There are two main directions in the lab:

(1) How do neural progenitors switch from progenitor states to differentiated states?

Previously, we showed that dynamic regulation of Notch and Hedgehog signaling plays an essential role in correct differentiation of neural progenitors. We will study the in vivo dynamics of Hedgehog and Notch signaling and determine the molecular interactions between these two pathways. We will also develop new imaging tools to visualize and manipulate cell signaling activity at single cell resolution in vivo.

(2) How is muscle integrity maintained?

Cilia are small cellular projections present on almost all vertebrate cells. We previously showed that cilia are essential for Hedgehog signaling but dispensable for Wnt signaling in zebrafish. Recently, we embark on a new but exciting project to explore the connection between muscle maintenance, cilia, Hedgehog signaling and muscular dystrophy. Understanding these processes will inform strategies to promote organ regeneration and repair.

Gagnon, J. A., Valen, E., Thyme, S. B., Huang, P., Ahkmetova, L., Pauli, A., Montague, T. G., Zimmerman, S., Richter, C. and Schier, A. F. (2014) Efficient Mutagenesis by Cas9 Protein-Mediated Oligonucleotide Insertion and Large-Scale Assessment of Single-Guide RNAs. PLoS One 9(5): e98186 Sittaramane, V., Pan, X., Glasco, D. M., Huang, P., Gurung, S., Bock, A., Li, S., Wang, H., Kawakami, K., Matise, M. P., Chandrasekhar, A. (2013). The PCP Protein Vangl2 Regulates Migration of Hindbrain Motor Neurons by Acting in Floor Plate Cells, and Independently of Cilia Function. Dev Biol 382 (2), 400-412. Xiong, F., Tentner, A. R., Huang, P., Gelas, A., Mosaliganti, K. R., Souhait, L., Rannou, N., Swinburne, I. A., Obholzer, N. D., Cowgill, P. D., Schier, A. F., and Megason, S. G. (2013). Specified Neural Progenitors Sort to Form Sharp Domains after Noisy Shh Signaling. Cell 153, 550–561. Huang, P.*, Xiong, F., Megason, S. G., and Schier, A. F.* (2012). Attenuation of Notch and Hedgehog signaling is required for fate specification in the spinal cord. PLoS Genet 8(6): e1002762. * co-corresponding authors. Stooke-Vaughan, G. A., Huang, P., Hammond, K. L., Schier, A. F., and Whitfield, T. T. (2012). The role of hair cells, cilia and ciliary motility in otolith formation in the zebrafish otic vesicle.Development 139:1777-87. Huang, P.* and Schier, A. F.* (2009). Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia. Development 136, 3089-98. * co-corresponding authors. Mao, J.*, McGlinn, E.*, Huang, P., Tabin, C. J. and McMahon, A. P. (2009). Fgf-dependent Etv4/5 activity is required for posterior restriction of Sonic Hedgehog and promoting outgrowth of the vertebrate limb. Dev Cell 16, 600-6. * co-first authors.