Nobuo Horikoshi, Ph.D.

DEPARTMENT OF Radiation Oncology
Keywords: apoptosis, cancer, tumor suppressor, tumorigenesis

Approximately 6.5 million people worldwide are diagnosed with cancer every year. It is clear that a thorough understanding of the molecular mechanisms of tumorigenesis is essential for the prevention, diagnosis and treatment of human cancer. Dr. Horikoshi’s long-term research focus is to develop protocols for effective radiation treatment of human cancer by establishing a detailed understanding of molecular recognition and function of p53 tumor suppressor in the processes of tumorigenesis.

One of his research interests is focused on the function of wild-type p53, especially for the better understanding of the mechanism of p53-dependent apoptosis. Dr. Horikoshi is particularly interested in elucidating the consequences of p53-dependent control of gene expressions and its possible role in apoptosis. This approach may provide new apoptotic genes that would enhance the cell-killing effect of irradiation and chemotherapy in cancer treatments.

Mutation in the p53 gene is often correlated pathologically with a large accumulation of mutant p53 protein in cells. Earlier work showed that some mutant p53s were actually tumorigenic and transformed cells with highly malignant properties. However, the molecular mechanisms of how mutant p53 contributes to a malignant transformation are largely unknown. The other part of Dr. Horikoshi research interest is the tumorigenic function of mutant p53. He is particularly interested in elucidating the involvement of mutant p53 in stress-response pathways. Irradiation and chemotherapy induce stress-response in cells that may, in part, induce cell death. If mutant p53 modifies stress-response pathways of cells, and therefore supports cell survival, this novel mechanism would reveal new targets of developing new drugs that interfere with the tumorigenic function of mutant p53. It is particularly important in the aspect of treatment of human cancer because results from our study may provide a clue to find a way of sensitizing cancer cells to irradiation or chemotherapy treatments, especially for cells carrying a mutation in the p53 gene.