He, Tong-Chuan, M.D., Ph.D.

Deregulation of Wnt/beta-catenin Signaling in Human Cancer; Molecular Biology of Bone and Soft Tissue Tumors; Gene Therapy.

Research Summary

Our research interests focus on the following three areas: 1) Elucidation of the molecular mechanisms underlying the activation of beta-catenin signaling during human tumorigenesis. Although beta-catenin has been shown to play an important role in human tumor development, little is known about how this pathway is activated in the majority of human cancer. We are interested in identifying the upstream activators of the beta-catenin pathway. We are also interested in studying the molecular genetics of bone and soft tissue tumors. 2) Elucidation of the molecular biology of bone formation. Understanding the molecular mechanisms of bone development and formation is pivotal for studying the pathogenesis of bone diseases. We are interested in identifying the critical factor(s) that regulate the proliferation and differentiation processes of osteoblasts and chondrocytes. Specifically, we are investigating the biological functions of bone morphogenetic proteins (BMPs) and other bone-specific transcription factors such as Runx2/Cbfa1 and Sox9. 3) Translational research and gene therapy. We are interested in developing innovative approaches for local or systemic delivery of therapeutic genes as effective treatment for human cancer and bone diseases.

Selected Papers

He T-C, Zhou S, da Costa L, Yu J, Kinzler KW and Vogelstein B: (1998). A simplified system for generating recombinant adenoviruses. Proceedings of National Academy of Sciences USA 95:2509-2514.

He T-C, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B and Kinzler KW: (1998). Identification of c-Myc as a target of the APC pathway. Science, 281:1509-1512.

He T-C, Chan TA, Vogelstein B and Kinzler KW: (1999). PPAR delta is an APC regulated target of nonsteroidal anti-inflammatory drugs. Cell 99:335-345.

Breyer B, Jiang W, Cheng H, Zhou L, Paul R, Feng T and He T-C: (2001). Adenoviral vector-mediated gene transfer for human gene therapy. Current Gene Therapy 1(2): 149-162.

He T-C. (2001). Unit 12.4: Adenoviral Vectors, in Current Protocols in Human Genetics John Wiley & Sons, Inc., New York, pp12.4.1-12.4.21.

Park BH, Breyer B and He T-C: (2001). Peroxisome proliferation-activated receptors: roles in tumorigenesis and chemoprevention in human tumor. Current Opinion in Oncology 13:78-83.

Jiang W, Zhou L, Breyer B, Feng T, Cheng H, Haydon R, Ishikawa A and He T-C: (2001). Tetracycline-regulated gene expression mediated by a novel chimeric repressor that recruits histone deacetylases in mammalian cells. Journal of Biological Chemistry 276 (48): 45168-45174.

Haydon RC, Zhou L, Feng T, Breyer B, Cheng H, Jiang W, Peabody T, Montag A, Simon MA and He T-C: (2002). Nuclear receptor agonists as potential differentiation therapy agents for human osteosarcoma. Clinical Cancer Research 8: 1288-1294.

Haydon RC, Deyrup A, Ishikawa A, Heck R, Jiang W, Zhou L, Feng T, King E, Cheng H, Breyer B, Peabody T, Simon M, Montag A and He T-C: (2002). Cytoplasmic and/or Nuclear Accumulation of the beta-Catenin Protein is a Frequent Event in Human Osteosarcoma. International Journal of Cancer. 102(4):338-342.

He T-C. (2002). Association of COX-2 and PPARs in Carcinogenesis and Chemoprevention. In COX-2 Blockade in Cancer Prevention and Therapy, Ed. R. E. Harris, Humana Press, Inc., New Jersey. pp225-244.

Zhou L, An N, Jiang W, Haydon R, Cheng H, Zhou Q, Breyer B, Feng T and He T-C: (2002). Fluorescence-based Functional Assay for the Wnt/beta-Catenin Signaling Activity. BioTechniques 33(5):1126-1135.

Zhou L, An N, Haydon RC, Zhou Q, Cheng H, Peng Y, Jiang W, Vanichakarn P, Szatkowski JP, Park JY, Breyer B and He T-C: (2003). Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the b-catenin signaling activity. Cancer Letters 193(2): 161-170.

Deyrup AT, Haydon RC, Huo D, Ishikawa A, Peabody TD, He T-C and Montag AG: (2003). Myoid Differentiation And Prognosis In Adult Pleomorphic Sarcomas Of The Extremity: An Analysis Of 93 Cases. Cancer 98 (4): 805-813.

Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L, Luu HH, An N, Breyer B, Vanichakarn P, Szatkowski JP, Park JY and He T-C: (2003). Osteogenic Activity of the 14 Types of Human Bone Morphogenetic Proteins (BMPs). Journal of Bone and Joint Surgery 85(8): 1544-1552.

Peng Y, Kang Q, Cheng H, Li X, Sun MH, Jiang W, Luu HH, Park JY, Haydon RC and He T-C: (2003). Transcriptional Characterization of Bone Morphogenetic Proteins (BMPs)-Mediated Osteogenic Signaling. Journal of Cellular Biochemistry 90: 1149-1165.

Luo J, Sun MH, Kang Q, Peng Y, Jiang W, Luu HH, Luo Q, Park JY, Li Y, Haydon RC and He T-C: Gene Therapy for Bone Regeneration. Current Gene Therapy (in press).