Pathology

Cancer Pathology

  • Professor: Shinya Tanaka
  • Associate Professor: Masumi Tsuda
  • Lecturer: Mishie Tanino
  • Assistant Professor: Hirokazu Sugino
  • Assistant Professor: Wang Lei
  • Phone: +81-11-706-7806
  • FAX: +81-11-706-5902
The philosophy of our lab is to enjoy medical science, and the main purposes of our projects are to uncover the disease mechanisms especially focusing on human cancers, to develop a new pathological diagnostic system, and to discover the new therapeutic drugs. For these goals, in addition to the molecular-based research, our laboratory performs various pathological activities including surgical diagnosis, autopsy, and molecular diagnosis. The advantage of our lab is that one can evaluate the individual new finding of the experiment in terms of whether it is a bona fide new discovery by the combination of molecular techniques and pathological human materials for various diseases. To date, students/research associates from China, Germany, Switzerland, Finland, Burundi, and Taiwan have studied at our lab.

Research

1.Signal transduction for cancer development. We are focusing on the signaling adaptor protein CRK. We have isolated human c-CRK and also its target molecules such as C3G and DOCK180, which are activators for small G proteins. CRK transmits signals from tyrosine kinases to small G proteins. CRK has been demonstrated to be an essential molecule for the malignant potential of various human cancers and thus should be a therapeutic target. Recently, we demonstrated the 3D structure of CRK, and based on the structure, the CRK signal inhibitor for cancer cell invasion is expected to be generated.
2.Bain tumor and neuropathology. To uncover the molecular mechanism of brain tumors and discover the new therapeutic reagents, we are trying to establish human glioblastoma models which are completely identical to the patient's original tumors. Brain tumor stem cells with CD133 positivity are also analyzed. For the treatment of glioblastoma by temozolomide, we have proposed a new approach for the evaluation of the MGMT status.
3.Clinical and translational pathology. Methodologically, microscopy-based time-lapse analysis with FRET, FISH, IHC, and immunoelectron microscopy are strong diagnostic and research tools in our lab. The following ongoing projects are of clinical significance: (i) Synovial sarcoma and SYT-SSX. (ii) Colon cancer and Cox-2. (iii) Respiratory system diseases including mesothelioma and pulmonary fibrosis. (iv) Hematopoietic cell specific DOCK2 research. (v) We accepted the evaluation of JC virus infection and the diagnosis for PML (progressive multifocal leukoencephalopathy) as a consultation.

Education

1.For medical students. We are presenting the classes for Pathology, Pathology practice, and Pathophysiology.
2.For Graduate course students. We are presenting the classes for Pathology, and tumor pathology.
3.For pathology residents. We are involved in the education of autopsy and surgical pathology diagnosis, and also clinico-pathological conference (CPC).

Related Staff

Department of Translational Pathology

  • Professor: Shinya Tanaka*
  • Professor: Hiroshi Nishihara
  • Assistant Professor: Wang Lei
  • Assistant Professor: Taichi Kimura*
  • *concurrent
1 Crk localized at focal adhesions (green). Actin stress fiber (red).
2 Structural analysis of signaling adaptor protein Crk.
3 Synovial sarcoma associated gene SYT deficient mouse embryo.
4 Brain tumor with temozolomide resistance. Inset is MGMT immunopositive.
5 Lab members at Noboribetsu Hot spring. June 28, 2008.
Fig1 Fig2 Fig3 Fig4 Fig5

International Activities

Editorial Board
Shinya Tanaka, Cell Communication and Signaling
Reviewer Board
Shinya Tanaka, Japanese Journal of Clinical Oncology
International meeting
  • Nishihara, H. AACR Annual Meeting. San Diego, USA, 2008
  • Tanaka, S.,et al. Cold Spring Harbor Meeting: Phosphorylation, signaling and Disease. Cold Spring Harbor, New York, USA, 2007
  • Sasai K, et al. Nature-CINO Conference: Oncogenes and Human Cancer: The Next 25 Years. Madrid, Spain, 2007
  • Tanaka, S. The Fifth Sino-Japan Joint Conference for Cancer Research. Shanghai, China, 2006 (invited)
International collaboration
We have collaborated with Dr. William W. Hall (College of Dublin, Irland), Dr. Stephan M. Feller (Oxford Univ., UK), Raymond Birge (New Jersey Medical Center, USA), and Dr. Marc Ladanyi (Memorial Sloan-Kettering Cancer Center, USA).

Selected Publications

1. Sasai, K., Nodagashira, M., Nishihara, H., et al.: Careful exclusion of non-neoplastic brain components is required for an appropriate evaluation of O6-methylguanine-DNA methyltransferase status in glioma: relationship between immunohistochemistry and methylation analysis. Am. J. Surg. Pathol., 32, 1220-1227, 2008.
2. Satoh, T., et al.: PILR is a herpes simplex virus-1 entry co-receptor that associates with glycoprotein B. Cell, 132, 935-944, 2008.
3. Kobashigawa, Y., Sakai, M., et al.: Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK. Nature Strct. & Mol. Biol., 6, 503-510, 2007.
4. Linghu, H., Tsuda, M., Makino, Y., et al.: Involvement of adaptor protein Crk in malignant feature of human ovarian cancer cell line MCAS. Oncogene, 25, 3547-3556, 2006.
5. Nishihara, H., Maeda, M., Oda, A., et al.: DOCK2 associates with CrkL and regulates Rac1 in hematopoietic cells. Blood, 100, 3968-3974, 2002.
6. Nagai, M., Tanaka, S., Tsuda, M., et al.: Analysis of transforming activity of human synovial sarcoma-associated chimeric protein SYT-SSX1 bound to chromatin remodeling factor hBRM/hSNF2. Proc.Natl.Acad.Sci.USA, 98, 3843-3848, 2001.
7. Tanaka, S., et al.: C3G, a guanine nucleotide releasing protein expressed ubiquitously binds to the SH3 domain of CRK and GRB2/ASH. Proc.Natl.Acad.Sci.USA, 91, 3443-3447, 1994.