Hisashi Tanaka, MD, PhD
Hisashi Tanaka, MD, PhD
The research goal of Hisashi Tanaka, MD, PhD, is to promote innovative diagnostic and treatment approaches for breast cancer through scientific discoveries, in particular the discoveries in the mechanisms of genome instability. Genome instability is an enabling characteristic through which tumor cells acquire indefinite proliferation and metastatic capabilities. Genome instability originates from deficiencies in DNA replication and repair functions. Thus better understanding of DNA damage and repair mechanisms is crucial and leads to the improved management of cancer patients. This is very important for breast cancer, because deficiencies in DNA replication and repair underlie the etiologies of familial breast cancer (BRCA1 and BRCA2 tumors) and an aggressive tumor subtype (HER2 amplification). Furthermore, cancer treatments often employ DNA-damaging agents (radiation, chemotherapy etc.). Tanaka's major research accomplishment is defining molecular mechanisms underlying gene amplification (palindromic gene amplification). Gene amplification is initiated by DNA breaks and drives the development of aggressive tumors, such as tumors at advanced stages and therapy-resistant tumors. At Cedars-Sinai, Tanaka is expanding his mechanism study to investigate how cells acquire DNA breaks that lead to genome instability. DNA breaks could occur during replication, when DNA is most vulnerable. However, because DNA replication is a dynamic process, investigations of DNA replication have been limited. Tanaka and his colleagues have overcome the problems and are now able to investigate the dynamic processes leading to gene amplification. He also gained insights on human genetic variations and genome evolution, and has kept up with the quickly evolving fields of genome biology and human genetics. In summary, armed with expertise in concepts and methodologies, Tanaka is dedicated to developing innovative approaches for the care of cancer patients.
- Medical School: Kyoto University, 1988
- Doctorate: Kyoto University Graduate School of Medicine, 1997
- Post Doctorate: Fred Hutchinson Cancer Research Center, 2003
Awards & Activities
- American Association for Cancer Research, 2007
- Kondratova A, Watanabe T, Marotta M, Cannon M, Serre D, Segall A, Tanaka H. Replication fork integrity and intra-S phase checkpoint suppress gene amplification. Nucleic Acids Res. 2015;43(5):2678–2690.
- Marotta M, Chen X, Watanabe T, Faber PW, Diede SJ, Tapscott S, Tubbs R, Kondratova A, Stephens R, Tanaka H. Homology-mediated end-capping as a primary step of sister chromatid fusion in the breakage-fusion-bridge cycles. Nucleic Acids Res. 2013;41(21):9732-9740.
- Marotta M, Chen X, Inoshita A, Stephens R, Thomas Budd G, Crowe JP, Lyons J, Kondratova A, Tubbs R, Tanaka H. A common copy-number breakpoint of ERBB2 amplification in breast cancer colocalizes with a complex block of segmental duplications. Breast Cancer Res. 2012;14(6):R150.
- Tanaka H, Yao MC. Palindromic gene amplification--an evolutionarily conserved role for DNA inverted repeats in the genome. Nat Rev Cancer. 2009;9(3):216-224.
- Zhao Y, Marotta M, Eichler EE, Eng C, Tanaka H. Linkage disequilibrium between two high-frequency deletion polymorphisms: implications for association studies involving the glutathione-S transferase (GST) genes. PLoS Genet. 2009;5(5):e1000472.
- Tanaka H, Bergstrom DA, Yao MC, Tapscott SJ. Widespread and nonrandom distribution of DNA palindromes in cancer cells provides a structural platform for subsequent gene amplification. Nat Genet. 2005;37(3): 320-327.