Tong-Chuan He

(1) Wnt and BMP signaling in stem cell proliferation and differentiation. Wnt and BMP signaling pathways play an important role in development. Using pluripotent mesenchymal stem cells (MSCs) we have demonstrated that the 14 types of BMPs exhibit distinct roles in regulating linage commitments of MSCs. We have also illustrated the distinct functions of the 19 Wnt factors in regulating lineage-specific differentiation of MSCs. Furthermore, there is a cross-talk between Wnt and BMP pathways. We are interested in identifying the key signaling mediators that regulate stem cell differentiation and that control lineage divergences. (2) Defects in stem cell differentiation and tumorigenesis. The essence of genetic and epigenetic changes in cancer cells is intended to disrupt the differentiation pathways. We have found that bone tumor cells fail to undergo terminal differentiation. In fact, the bone tumor cells are refractory to differentiation signals, and even convert differentiation cues into proliferation signals. We are interested in identifying critical differentiation defects that may hold keys to unlock tumorigenesis. (3) Interactions between tumors and stromal cells in bone metastasis. Interactions between disseminated cancer cells and bone marrow stromal cells (aka bone marrow mesenchymal stem cells, bMSCs) may play an important role in controlling the survival and colonization of bone metastasis. Using bone metastasis animal models, we are interested in elucidating the roles of bMSC-derived factors in the development of bone metastasis. (4) Targeted therapies and regenerative medicine. Identification of differentiation defects in tumors would allow us to develop novel differentiation therapies that circumvent the defective stages. Accordingly, the bMSC-derived factors may serve as cancer drug targets. The critical regulators of stem cell differentiation may be used for stem cell-based and/or gene therapies in tissue regeneration.

(1) Wnt and BMP signaling in stem cell proliferation and differentiation. Wnt and BMP signaling pathways play an important role in development. Using pluripotent mesenchymal stem cells (MSCs) we have demonstrated that the 14 types of BMPs exhibit distinct roles in regulating linage commitments of MSCs. We have also illustrated the distinct functions of the 19 Wnt factors in regulating lineage-specific differentiation of MSCs. Furthermore, there is a cross-talk between Wnt and BMP pathways. We are interested in identifying the key signaling mediators that regulate stem cell differentiation and that control lineage divergences. (2) Defects in stem cell differentiation and tumorigenesis. The essence of genetic and epigenetic changes in cancer cells is intended to disrupt the differentiation pathways. We have found that bone tumor cells fail to undergo terminal differentiation. In fact, the bone tumor cells are refractory to differentiation signals, and even convert differentiation cues into proliferation signals. We are interested in identifying critical differentiation defects that may hold keys to unlock tumorigenesis. (3) Interactions between tumors and stromal cells in bone metastasis. Interactions between disseminated cancer cells and bone marrow stromal cells (aka bone marrow mesenchymal stem cells, bMSCs) may play...

Ni Tang, Wen-Xin Song, Jinyong Luo, Xiaoji Luo, Jin Chen, Katie A.Sharff, Yang Bi, Bai-Cheng He, Jia-Yi Huang, Gao-Hui Zhu, Yu-Xi Su, Wei Jiang, Min Tang, Yun He, Yi Wang, Liang Chen, Guo-Wei Zuo, Jikun Shen, Xiaochuan Pan, Russell R. Reid, Hue H. Luu, Rex C. Haydon, and Tong-Chuan He: (2009) BMP9-induced osteogenic differentiation of mesenchymal progenitors requires functional canonical Wnt/beta-catenin signaling. Journal of Cellular and Molecular Medicine [in press].  

Quan Kang, Wen-Xin Song, Qing Luo, Ni Tang, Jinyong Luo, Xiaoji Luo, Jin Chen, Yang Bi, Bai-Cheng He, Jong Kyung Park, Wei Jiang, Yi Tang, Jiayi Huang, Yuxi Su, Gao-Hui Zhu, Yun He, Hong Yin, Zhenming Hu, Yi Wang, Liang Chen, Guowei Zuo, Xiaochuan Pan, Jikun Shen, Tamara Vokes, Russell Reid, Rex C. Haydon, Hue H. Luu, and Tong-Chuan He: (2009) A Comprehensive Analysis of the Dual Roles of BMPs in Regulating Adipogenic and Osteogenic Differentiation of Mesenchymal Progenitor Cells. Stem Cells and Development 18(4): 545-559 

Katie A. Sharff, Wen-Xin Song, Xiaoji Luo, Ni Tang, Jinyong Luo, Jin Chen, Yang Bi, Bai-Cheng He, Jiayi Huang, Xinmin Li, Wei Jiang, Gao-Hui Zhu, Yuxi Su, Yun He, Jikun Shen, Yi Wang, Liang Chen, Guo-Wei Zuo, Bo Liu, Xiaochuan Pan, Russell R. Reid, Hue H. Luu, Rex C. Haydon, and Tong-Chuan He: (2009) Hey1 Basic Helix-Loop-Helix (bHLH) Protein Plays an Important Role in Mediating BMP9 Induced Osteogenic Differentiation of Mesenchymal Progenitor Cells. Journal of Biological Chemistry 284(1): 649-659 

Xiaoji Luo, Jin Chen, Wen-Xin Song, Ni Tang, Jinyong Luo, Zhong-Liang Deng, Katie A. Sharff, Gary He, Yang Bi, Bai-Cheng He, Erwin Bennett, Jiayi Huang, Quan Kang, Wei Jiang, Yuxi Su, Gao-Hui Zhu, Hong Yin, Yun He, Yi Wang, Jeffrey S. Souris, Liang Chen, Guo-Wei Zuo, Anthony G. Montag, Russell Reid, Rex C. Haydon, Hue H. Luu, and Tong-Chuan He: (2008) Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects. Laboratory Investigation 88(12):1264-1277. 

Jinyong Luo, Zhong-Liang Deng, Xiaoji Luo, Ni Tang, Wen-Xin Song, Jin Chen, Katie A. Sharff, Hue H. Luu, Rex C. Haydon, Kenneth W. Kinzler, Bert Vogelstein, and Tong-Chuan He: (2007) A protocol for rapid generation of recombinant adenoviruses using the AdEasy system. Nature Protocols 2(5): 1236-1247 

Weike Si, Quan Kang, Hue H. Luu, Jong Kyung Park, Qing Luo, Wen-Xin Song, Wei Jiang, Xiaoji Luo, Xinmin Li, Hong Yin, Anthony G. Montag, Rex C. Haydon, and Tong-Chuan He: (2006) CCN1/Cyr61 is regulated by canonical Wnt signal and plays an important role in Wnt3A-induced early osteogenic differentiation. Molecular and Cellular Biology 26(8):2955 2964. 

Qing Luo, Quan Kang, Weike Si, Wei Jiang, Jong Kyung Park, Ying Peng, Xinmin Li, Hue H. Luu, Jeffrey Luo, Anthony G. Montag, Rex C. Haydon, and Tong-Chuan He: (2004) Connective Tissue Growth Factor (CTGF) is regulated by Wnt and BMP signaling in osteoblast differentiation of mesenchymal stem cells. Journal of Biological Chemistry 279 (53): 55958-55968. 

Quan Kang, Michael H. Sun, Hongwei Cheng*, Ying Peng, Anthony G. Montag, Andrea T. Deyrup, Wei Jiang, Hue H. Luu, Jan Paul Szatkowski, Pantila Vanichakarn, Jae Yoon Park, Jeffrey Luo, Yien Li, Rex C. Haydon, and Tong-Chuan He: (2004) Characterization of the distinct orthotopic bone forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery. Gene Therapy 11 (17): 1312–1320. 

Hue H. Luu, Ruiwen Zhang, Rex C. Haydon, Elizabeth Rayburn, Quan Kang, Weike Si, Jong Kyung Park, Hui Wang, Ying Peng, Wei Jiang, and Tong-Chuan He: (2004) Wnt/beta-Catenin Signaling Pathway as a Novel Cancer Drug Target. Current Cancer Drug Targets 4: 653-671. 

Ying Peng, Quan Kang, Qing Luo, Wei Jiang, Weike Si, Bernard A. Liu, Hue H. Luu, Jong Kyung Park, Xinmin Li, Jeffrey Luo, Anthony G. Montag, Rex C. Haydon, and Tong-Chuan He: (2004) Id Helix-Loop-Helix Proteins Mediate BMP-induced Osteoblast Differentiation of Mesenchymal Stem Cells. Journal of Biological Chemistry 279(31): 32941-32949. 

Ying Peng, Quan Kang, Hongwei Cheng, Xinmin Li, Michael H. Sun, Wei Jiang, Hue H. Luu, Jae Yoon Park, Rex C. Haydon, and Tong-Chuan He: (2003) Transcriptional Characterization of Bone Morphogenetic Proteins (BMPs)-Mediated Osteogenic Signaling. Journal of Cellular Biochemistry 90: 1149-1165. 

Tong-Chuan He, Timothy A. Chan, Bert Vogelstein, and Kenneth W. Kinzler: (1999) PPAR delta is an APC regulated target of nonsteroidal anti-inflammatory drugs. Cell 99:335-345. 

Tong-Chuan He, Shibin Zhou, Luis da Costa, Jian Yu, Kenneth W. Kinzler, and Bert Vogelstein: (1998) A simplified system for generating recombinant adenoviruses. Proceedings of National Academy of Sciences USA 95:2509-2514. 

Tong-Chuan He, Andrew B. Sparks, Carlo Rago, Heiko Hermeking, Leigh Zawel, Luis T. da Costa, Patrice J. Morin, Bert Vogelstein, and Kenneth W. Kinzler. (1998) Identification of c-Myc as a target of the APC pathway. Science 281:1509-1512.  

Ni Tang, Wen-Xin Song, Jinyong Luo, Xiaoji Luo, Jin Chen, Katie A.Sharff, Yang Bi, Bai-Cheng He, Jia-Yi Huang, Gao-Hui Zhu, Yu-Xi Su, Wei Jiang, Min Tang, Yun He, Yi Wang, Liang Chen, Guo-Wei Zuo, Jikun Shen, Xiaochuan Pan, Russell R. Reid, Hue H. Luu, Rex C. Haydon, and Tong-Chuan He: (2009) BMP9-induced osteogenic differentiation of mesenchymal progenitors requires functional canonical Wnt/beta-catenin signaling. Journal of Cellular and Molecular Medicine [in press].  

Quan Kang, Wen-Xin Song, Qing Luo, Ni Tang, Jinyong Luo, Xiaoji Luo, Jin Chen, Yang Bi, Bai-Cheng He, Jong Kyung Park, Wei Jiang, Yi Tang, Jiayi Huang, Yuxi Su, Gao-Hui Zhu, Yun He, Hong Yin, Zhenming Hu, Yi Wang, Liang Chen, Guowei Zuo, Xiaochuan Pan, Jikun Shen, Tamara Vokes, Russell Reid, Rex C. Haydon, Hue H. Luu, and Tong-Chuan He: (2009) A Comprehensive Analysis of the Dual Roles of BMPs in Regulating Adipogenic and Osteogenic Differentiation of Mesenchymal Progenitor Cells. Stem Cells and Development 18(4): 545-559 

Katie A. Sharff, Wen-Xin Song, Xiaoji Luo, Ni Tang, Jinyong Luo, Jin Chen, Yang Bi, Bai-Cheng He, Jiayi Huang, Xinmin Li, Wei Jiang, Gao-Hui Zhu, Yuxi Su, Yun He, Jikun Shen, Yi Wang, Liang Chen, Guo-Wei Zuo, Bo Liu, Xiaochuan Pan, Russell R. Reid, Hue H. Luu, Rex C. Haydon, and Tong-Chuan He: (2009) Hey1 Basic Helix-Loop-Helix (bHLH) Protein Plays an Important Role in Mediating BMP9 Induced Osteogenic Differentiation of Mesenchymal Progenitor Cells. Journal of Biological Chemistry 284(1): 649-659 

Xiaoji Luo, Jin Chen, Wen-Xin Song, Ni Tang, Jinyong Luo, Zhong-Liang Deng, Katie A. Sharff, Gary He, Yang Bi, Bai-Cheng He, Erwin Bennett, Jiayi Huang, Quan Kang, Wei Jiang, Yuxi Su, Gao-Hui Zhu, Hong Yin, Yun He, Yi Wang, Jeffrey S. Souris, Liang Chen, Guo-Wei Zuo, Anthony G. Montag, Russell Reid, Rex C. Haydon, Hue H. Luu, and Tong-Chuan He: (2008) Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects. Laboratory Investigation 88(12):1264-1277. 

Jinyong Luo, Zhong-Liang Deng, Xiaoji Luo, Ni Tang, Wen-Xin Song, Jin Chen, Katie A. Sharff, Hue H. Luu, Rex C. Haydon, Kenneth W. Kinzler, Bert Vogelstein, and Tong-Chuan He: (2007) A protocol for rapid generation of recombinant adenoviruses using the AdEasy system. Nature Protocols 2(5): 1236-1247