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About Sickkids
About SickKids

Chi-chung Hui, PhD

Research Institute
Senior Scientist
Developmental & Stem Cell Biology

University of Toronto
Professor
Department of Molecular Genetics


Phone: 416-813-4994
Fax: 416-813-5252
Email: cchui@sickkids.ca

For more information, visit:

Hui lab

Research Interests

  • Hedgehog signal transduction
  • Iroquois homeodomain transcription factors
  • Animal and stem cell models of basal cell carcinoma and medulloblastoma
  • Limb patterning, neuronal cell specification and skin development
  • Heart development and function

Research Activities

Hedgehog signaling in development and disease
The Hedgehog (Hh) signaling pathway plays critical roles in embryonic development and tissue homeostasis. In humans, aberrations in the Hh signaling pathway lead to congenital malformations and cancer. My laboratory is interested in understanding the molecular mechanisms underlying Hh signal transduction in mammalian cells and how Hh signaling contributes to normal development as well as diseases, including cancer.

We have shown that three Gli transcription factors are involved in mammalian Hh signal transduction. Through modulation of both activator and repressor functions of these transcription factors, Hh signaling controls cell specification, differentiation, and proliferation. To investigate how the activity of these transcription factors are regulated, we have been studying the interactions of Gli proteins with several Hh pathway components, including the Hh receptors Ptch1 and Ptch2, Suppressor of fused, and Kif7, and examining the role of these molecules in Hh signaling.

My laboratory focuses on the nervous system and skin because Hh signaling is required for normal development of these tissues and abnormal activation of the Hh pathway results in brain and skin tumours. Ongoing studies are directed to elucidate the cellular and molecular events that are involved in the normal and abnormal development of these organs.


Iroquois homeodomain transcription factors
In humans and mice, there are six Iroquois homeobox (Irx) genes, which encode highly conserved TALE-class homeodomain containing transcription factors. Mutations in the human Irx4 and Irx5 genes have been found in congenital malformations with defects in heart and craniofacial development. My laboratory is using the mouse as a model to investigate the function of these Irx genes in embryonic development and adult physiology. Our genetic analysis revealed that the Irx genes possess unique as well as overlapping functions in both embryonic patterning and terminal differentiation. Ongoing studies are directed to decipher the molecular actions of these transcription factors in heart and limb development.

External Funding

  • Canadian Institutes of Health Research (CIHR)
  • Canadian Cancer Society Research Institute

Publications

For a complete list of publications, please see PubMed

Li ZJ, Mack SC, Mak TH, Angers S, Taylor MD, Hui CC. (2013) Evasion of p53 and G2/M checkpoints are characteristic of Hh-driven basal cell carcinoma. Oncogene. June 10.

Law KK, Makino S, Mo R, Zhang X, Puviindran V, Hui CC. (2013) Antagonistic and cooperative actions of Kif7 and Sufu define graded intracellular Gli activities in Hedgehog signaling. PLoS One. 7(11):e50193.

Li ZJ, Nieuwenhuis E, Nien W, Zhang X, Zhang J, Puviindran V, Wainwright BJ, Kim PC, Hui CC. (2012) Kif7 regulates Gli2 through Sufu-dependent and -independent functions during skin development and tumorigenesis. Development. 139(22):4152-61.

Kim KH, Rosen A, Bruneau BG, Hui CC, Backx PH. (2012) Iroquois homeodomain transcription factors in heart development and function. Circulation Research. 110(11):1513-1524.

Hsu S-HC, Zhang X, Yu C, Li ZS, Wunder JS, Hui CC, Alman BA.  (2011) Kif7 promotes Hedgehog signaling in growth plate chondrocytes by restricting the inhibitory function of Sufu. Development. 138(17):3791-380.

Hui CC, Angers S. (2011) Gli proteins in development and disease. Annual Review of Cell and Developmental Biology. 27: 513-537.

Zhang S-S, Kim K-H, Rosen A, Smyth JW, Sakuma R, Delgado-Olguin P, Davis M, Chi NC, Puviindran V, Gaborit N, Sukonnik T, Wylie JN, Brand-Arzamendi K, Farman G, Kim J, Rose RA, Marsden PA, Zhu Y, Zhou Y-Q, Miquerol L, Henkelman RM, Stainier DYR, Shaw RM, Hui CC, Bruneau BG, Backx PH. (2011) Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network. Proceedings of the National Academy of Sciences USA. 108(33):13576-81.

Kim JJ-E, Gill P, Rotin L, van Eede M, Henkelman R, Hui CC, Rosenblum ND. (2011) Suppressor of fused controls mid-hindbrain patterning and cerebellar morphogenesis via GLI3 repressor. Journal of Neurosciences. 31(5):1825-36.

Pospisilik JA, Schramek D, Schnidar H, Cronin SJF, Nehme NT, Zhang X, Puviindran V, Knauf C, Cani PD, Aumayr K, Todoric J, Bayer M, Tar K, Haschemi A, Puviindran V, Orthofer M, Neely GG, Dietzl G, Manoukian A, Funovics M, Prager G, Wagner O, Ferrandon D, Aberger F, Hui CC, Esterbauer H, Penninger J. (2010) Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate.  Cell. 140(1):148-160.

Cheung HO, Zhang X, Ribeiro A, Mo R, Makino S, Puviindran V, Law KK, Briscoe J, Hui CC. (2009) The kinesin protein Kif7 is a critical regulator of Gli transcription factors in mammalian hedgehog signaling.  Science Signaling. 2(76):ra29.

Chen MH, Wilson CW, Li YJ, Law KKL, Lu CS, Gacayan R, Zhang X, Hui CC, Chuang PT. (2009) Cilium-independent regulation of Gli proteins by Sufu in Hedgehog signaling is evolutionarily conserved.  Genes & Development. 23(16):1910-28.

Ward RJ, Lee L, Graham K, Satkunendran T, Yoshikawa K, Ling E, Harper L, Austin R, Nieuwenhuis E, Clarke ID, Hui CC, Dirks PB. (2009) Multipotent CD15+ cancer stem cells in patched1-deficient mouse medulloblastoma.  Cancer Research. 69(11):4682-90.

Jiang J, Hui CC. (2008) Hedgehog signaling in development and cancer. Developmental Cell. 15(6): 801-12.

Nieuwenhuis E, Barnfield PC, Makino S, Hui CC. (2007) Epidermal hyperplasia and expansion of the interfollicular stem cell compartment in mutant mice with a C-terminal truncation of Patched1. Developmental Biology. 308(2):547-60.

Lebel M, Mo R, Shimamura K, Hui CC. Gli2 and Gli3 play distinct roles in the dorsoventral patterning of the mouse hindbrain. Developmental Biology. 302(1):345-55.

Nieuwenhuis E, Motoyama J, Barnfield PC, Yoshikawa Y, Zhang X, Mo R, Crackower MA, Hui CC. (2006) Mice with a targeted mutation of Patched2 are viable but develop alopecia and epidermal hyperplasia. Molecular and Cellular Biology. 26(17):6609-22.

Hu MC, Mo R, Bhella S, Wilson CW, Chuang P-T, Hui CC, Rosenblum ND. (2006) GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis. Development. 133(3:)569-78.

Cheng CW, Yan CHM, Strahle U, Hui CC, Cheng SH. (2006) The homeobox gene irx1a is required for the propagation of the neurogenic waves in the zebrafish retina. Mechanisms of Development. 123(3):252-63.

Cheng CW, Chow RL, Lebel M, Sakuma R, Cheung HO-L, Thanabalasingham V, Zhang X, Bruneau BG, Birch DG, Hui CC, McInnes RR, Cheng SH. (2005) The Iroquois homeobox gene, Irx5, is required for retinal cone bipolar cell development. Developmental Biology. 287(1):48-60.

Costantini DL, Arruda EP, Agarwal P, Kim K-H, Zhu Y, Zhu W, Lebel M, Cheng CW, Park CY, Pierce SA, Guerchicoff A, Pollevick GD, Chan TY, Kabir G, Cheng SH, Husain M, Antzelevitch C, Srivastava D, Gross GJ, Hui CC, Backx PH, Bruneau B. (2005) The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient. Cell 123(2):347-58.

Mill P, Mo R, Hu MC, Dagnino L, Rosenblum ND, Hui CC. (2005) Shh controls epithelial proliferation via independent pathways that converge on N-Myc. Developmental Cell. 9(2):293-303.

Intellectual Property

  • Transgenic mouse model of basal cell carcinoma