Basic Medicine, Immunology
Developing World-leading Pathologists
Medical Sciences Course
- Master / Doctoral Degree
- FURUKAWA, Toru
Professor, M.D. Ph.D
toru.furukawa*med.tohoku.ac.jp (Please convert "*" into "@".)
- Identification of molecular targets for intractable diseases by genomic analysis
- Understanding of pathobiology of intractable diseases by means of in vitro and in vivo modeling
- Development of world-leading pathologists, Development and training of surgical pathologists
Pathobiology of intractable diseases, Genome and diseases, Molecular pathology, Surgical pathology
Human pathology, Surgical pathology, Molecular pathology, Molecular biology, Cell biology
We carried out research of intractable diseases with employing advanced molecular and pathobiological techniques and genome analysis. Selected topics of our research are as follows:
1. Pancreatic cancer is characterized by persisting activation of ERK/MAPK. We discovered that the ERK/MAPK activation was a result of synergistic effects of mutated KRAS and inactivation of DUSP6. Moreover, we uncovered downstream effector molecules of ERK/MAPK by genome-wide expression screening and identified molecular targets useful for diagnosis and treatment of pancreatic cancer by genome-wide knockdown screening.
2. Intraductal papillary mucinous neoplasm of the pancreas (IPMN) is characterized by mucinous ductal dilatation lined by papillary neoplastic cells. We demonstrated pathological characteristics of this neoplasm and identified a specific molecular alteration, namely, GNAS mutation. In vitro functional analyses showed that the mutated GNAS induced global changing of gene expressions including upregulation of mucin genes in pancreatic ductal cells. We developed a genetically engineered mouse model capable of conditional expression of the mutated GNAS and demonstrated that the model mouse was able to develop IPMN by synergistic pancreas-specific expression of the mutated GNAS and a mutated Kras. These results indicate that GNAS mutation is a key specific driver gene of IPMN.
Figure 1. SON is a molecular target for treatment of pancreatic cancer (Mol Cancer 11:88, 2012)
Figure 2. IPMN shows overexpression of GNAS and activation of PKA (Sci Rep 1:161, 2011)
- Omori Y, Ono Y, Tanino M, Karasaki H, Yamaguchi H, Furukawa T, Enomoto K, Ueda J, Sumi A, Katayama J, Muraki M, Taniue K, Takahashi K, Ambo Y, Shinohara T, Nishihara H, Sasajima J, Maguchi H, Mizukami Y, Okumura T, Tanaka, S. Pathways of progression from intraductal papillary mucinous neoplasm to pancreatic ductal adenocarcinoma based on molecular features. Gastroenterology 156(3):647?661, 2019.
- Arima K, Ohmuraya M, Miyake K, Koiwa M, Uchihara T, Izumi D, Gao F, Yonemura A, Bu L, Okabe H, Imai K, Hashimoto D, Baba Y, Chikamoto A, Yamashita Y, Furukawa T, Araki K, Baba H. Inhibition of 15-PGDH causes Kras-driven tumor expansion through prostaglandin E2-ALDH1 signaling in the pancreas. Oncogene 38,?1211?1224, 2019.
- Takeuchi S, Doi M, Ikari N, Yamamoto M, Furukawa T. Mutations in BRCA1, BRCA2, and PALB2, and a panel of 50 cancer-associated genes in pancreatic ductal adenocarcinoma. Sci Rep 8:8105, 2018.
- Eto T, Miyake K, Nosh K, Ohmuraya M, Imamura Y, Arima K, Kanno S, Fu L, Kiyozumi Yuki 1, Izumi D, Sugihara H, Hiyoshi Y, Miyamoto Y, Sawayama H, Iwatsuki M, Baba Y, Yoshida N, Furukawa T, Araki K, Baba H, Ishimoto T. Impact of loss-of-function mutations at the RNF43 locus on colorectal cancer development and progression. J Pathol 245(4): 445?455, 2018.
- Basturk O, Berger MF, Yamaguchi H, Adsay V, Askan G, Bhanot UK, Zehir A, Carneiro F, Hong S-M, Zamboni G, Dikoglu E, Jobanputra V, Wrzeszczynski KO, Balci S, Allen P, Ikari N, Takeuchi S, Akagawa H, Kanno A, Shimosegawa T, Morikawa T, Motoi F, Unno M, Higuchi R, Yamamoto M, Shimizu K, Furukawa T, Klimstra DS. Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductalpapillary mucinous neoplasm and ductal adenocarcinoma. Mod Pathol 30(12): 1760?72, 2017.