Toshiyuki Yoneda, D.D.S., Ph.D.
980 W. Walnut St.
Walther Hall, R3 C321D
Indianapolis, IN 46202
Phone: (317) 274-3530
Fax: (317) 274-0396
Research Program Membership
Senior Research Professor
Department of Medicine
Division of Hematology/Oncology
IU School of Medicine
Current research interests 1. Epithelial-mesenchymal transition (EMT) of breast cancer in bone Clinical data are accumulating that the presence of disseminated tumor cells (DTC) in bone marrow significantly decreases overall survival (OS) in breast cancer patients. We hypothesize that DTC of breast cancer is promoted to undergo EMT under the influences of bone microenvironment, thereby acquiring further aggressiveness. We will study the underlying mechanism of EMT of breast cancer in bone in vivo and in vitro. We will also attempt to design pharmacological inhibition of breast cancer EMT. 2. Molecular mechanism of bone pain associated with bone metastasis One of the major complications of bone metastasis is intractable bone pain. Bone pain significantly affects quality of life and eventually survival of cancer patients with bone metastasis. However the current treatments for bone pain are palliative, unsatisfactory and inappropriate primarily due to poor understanding of the mechanism of bone pain. We will study the molecular mechanism of bone pain using animal models of bone pain we have developed and in vitro models that can represent intracellular signaling events elicited following bone pain. Identification of molecules involved in causing bone pain is expected to lead us to design novel analgesic agents. 3. Osteonecrosis of the jaw Patients receiving bisphosphonate (BP) and denosumab (Dmab) for the treatment of osteoporosis or bone metastasis occasionally develop osteonecrosis of the jaw (ONJ) after invasive dental treatments such as tooth extraction and dental implants. Although the frequency of ONJ is not high, ONJ is extremely difficult to cure and hampers the maintenance of oral health. We will study the pathophysiology of ONJ by developing animal model of ONJ. It is noted that there is no reproducible and consistent animal model of ONJ at present. Since BP and Dmab are specific inhibitors of osteoclastic bone resorption, osteoclasts probably play a critical role in the pathophysiology of ONJ. We will also seek the possibility that non-osteoclast-mediated mechanisms are involved. Future research interests Mechanism of lymphatic metastasis of oral cancers It has been well recognized that lymph node metastasis strongly correlates with the risk to survival in patients with oral cancers. Oral cancer patients without lymph node metastases have a cumulative survival rate of approximately 50-70%, this rate drops significantly to 30-50% in patients with lymph node metastases. Importantly, inhibition of lymph node metastasis was associated with reduced distant organ metastasis in animal models of cancer, suggesting there may be a pathway facilitating distant organ metastasis via the lymph nodes. Thus, understanding the pathophysiology of lymph node metastasis of oral cancer is important for early diagnosis and treatment. We will attempt to study molecular mechanisms of lymph node metastasis of oral cancer.
Post-doctoral Fellowship - University of Connecticut Health Center, CT 1979
Ph.D. - Osaka University Graduate School of Dentistry, Osaka, Japan 1976
D.D.S. - Osaka University School of Dentistry, Osaka, Japan 1972