Cedars Sinai Medical Center
United States of America
My career goal is to contribute to human health through scientific discoveries and innovations. During my 5-year career as a surgical oncologist, I saw many cancer patients who developed very aggressive tumors. Because none of the treatments were effective for those patients, I realized the necessity of transformational developments leading to new treatments for cancer patients. My research focuses on the mechanism of gene amplification, a process which drives aggressive tumor phenotypes, such as tumor progression and therapy resistance. I have provided novel insights on both genetic and genomic factors involved in gene amplification (Tanaka et al., 2002, 2005, 2007 and 2009; Marotta et al., 2012b and 2013). In my search for the mechanisms of gene amplification, I have developed novel cell-based and genome-wide assays. I have also gained deep insights on human genetic variation and genome evolution (Zhao et al., 2009; Marotta et al., 2012a), subjects that are important to understand the tumor cell evolution. More specifically, my recent research programs focus on the role of replication stress in the initiation of gene amplification. I am currently investigating the processes underlying naturally occurring stalled replication forks (Kondratova et al., in press; Watanabe et al., submitted). My program integrates knowledge from simple organisms and other model systems and test this knowledge in the setting of naturally occurring stalled forks in cancer cells. We believe that such a strategy will provide a novel insight into cancer genome instability. In summary, armed with expertise in both the concepts (cancer biology, human genetics and molecular evolution) and methodology (molecular biology, cell biology and genomics), I am dedicated to the development of interventions for novel cancer diagnostics and treatments.
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.