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

APPOINTMENTS

  • Associate Professor; Department of Surgery; Cancer Research Center; Committee on Cancer Biology; Committee on Genetics, Committee on Cell Physiology

EDUCATION

Ph.D., Pennsylvania State University
M.D., Chongqing University of Medical Sciences

CONTACT INFORMATION

The University of Chicago
SBRI J611B/MC 3079
5812 South Ellis Avenue
Chicago, Illinois 60637

tche@surgery.bsd.uchicago.edu

Phone: (773) 702-7169

Website (Cell Physiology)
Website (Molecular Oncology Laboratory)

RESEARCH SUMMARY

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

The Molecular Oncology Laboratory primarily focuses on the following areas: 

(1) The Wnt and BMP signaling pathways in stem cell proliferation and differentiation. It has been well established that both Wnt and BMP signaling pathways play an important role in development, as well as in embryonic and adult stem cell differentiation.  However, the precise mechanisms through which these signals exert their biological functions remain to be fully elucidated.  Using the pluripotent mesenchymal stem cells (MSCs) as a model system, 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 signaling pathways. We are interested in identifying the key signaling mediators that regulate stem cell proliferation and differentiation and that control the divergences of different lineages. 

(2)  Defects in stem cell differentiation and tumorigenesis.  As our knowledge about stem cells and cancer stem cells expands, it has become increasingly evident that cancer is not just a genetic disease but also a differentiation disease.  The essence of genetic and epigenetic changes in cancer cells is intended to disrupt the differentiation pathways in the affected cells. Using primary bone tumor (aka, osteosarcoma, a type of malignant pediatric tumors occurring at the growth plates of adolescent long bones) as a model system, we have found that bone tumor cells fail to undergo terminal differentiation, when compared with the normal preosteoblast progenitors. In fact, the bone tumor cells are refractory to differentiation signals, and even convert differentiation cues into proliferation signals. We are interested in identifying the critical differentiation defects that may hold the keys to unlock the pathogenesis of human tumors.   

(3)  Interactions between tumors and stromal cells in the development of bone metastasis.  Tumor microenvironment and cancer metastasis are two important but often overlooked areas in cancer research. Metastatic cells are a subset of primary tumor cells that have acquired the ability to complete a multi-step metastatic cascade, including migration, dissemination, extravasation, and eventual proliferation at a discontinuous secondary site.  Increasing evidence suggests that the interactions between disseminated cancer cells and bone marrow stromal cells (also referred to as bone marrow mesenchymal stem cells, bMSCs) may play an important role in controlling the survival and colonization of bone metastasis.  Using our unique bone metastasis animal models, we are interested in identifying and elucidating the roles of bMSC-derived factors in the development of bone metastasis (from breast cancer, prostate cancer, etc).

(4) Targeted therapies and regenerative medicine. The ultimate goal of biomedical research is to translate basic findings from bench to bedside. 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 proliferation and differentiation may be used as therapeutic genes for stem cell-based and/or gene therapies for tissue regeneration (such as bone and cartilage regeneration and tendon injury repair) and for the treatment of other bone and musculoskeletal disorders.

Research Papers in PubMed