Oncopathology and Regenerative Biology
Information for Exchange Students
Name of the department: Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki
Name of the research project: Molecular analysis of pericellular regulation of protease activity and tissue microenvironment in the physiological and pathological conditions
Head of the department: Professor Hiroaki Kataoka, MD, PhD
Assistant Professor Hiroyuki Tanaka, MD, PhD
Assistant Professor Tsuyoshi Fukushima, MD, PhD
Assistant Professor Kenji Yorita, MD, PhD
Research Associate Makiko Kawaguchi, PhD
Duration of the project: One month
Period of year: all year except from Dec. 25th to Jan. 6th
Acceptable number of students: 1/year
Description of the project: Cell-stroma and cell-cell interactions in pericellular microenvironment are critical for various biological phenomena both in the physiological and pathological conditions including cancer. Ample evidence indicates that normal microenvironment suppresses carcinogenesis even in the presence of strong oncogene expression. On the other hand, in established cancer tissue, interaction between cancer cells and cancer stroma in microenvironment is important determinant of malignant phenotypes such as sustained angiogenesis, escape from apoptosis and invasion/metastasis. Therefore, pericellular microenvironment can function both as a suppressor of carcinogenesis and as a promoter of cancer progression.
Regulation of protease activity on the cellular surface is one of the most important mechanisms to control the quality of microenvironment. Our research group has been studying the roles of pericellular microenvironment on the integrity of normal epithelial tissue and cancer progression, particularly focusing on the regulation of membrane-anchored serine proteases by a membrane-anchored Kunitz-type inhibitor, HAI-1 (hepatocyte growth factor activator inhibitor-1). By using genetically engineered mouse models, cultured cells and surgically resected tissue specimens, we have revealed critical roles of HAI-1 in the integrity of normal epithelial tissues and invasive growth of carcinoma cells, through specific interaction with its cognate cell surface protease expressed in each epithelial tissue and cancer cell.
In addition, our group also searching for a novel therapeutic molecular targets of treatment resistant human cancers, such as glioblastoma, pancreatic cancer and heptocellular carcinoma.
The students who join our laboratory would work on the proceeding project and learn techniques for histopathology and molecular biology as follows;
1. Pathological evaluation of tumor tissues.
2. Protein expression analysis using immunohistochemistry and immunoblotting
3. Handling and analyses of mRNA by reverse transcription PCR, real time-PCR, and in situ hybridization
4. Biological analysis in vitro using cell culture technique
5. Analyses of animal models, such as knockout mice (including conditional knock out mice) and tumor model mice
Aim of the project:
The aim of our projects is to know the roles of pericellular microenvironment in the cancer development and progression. A better understanding of cell-cell and cell-stroma interactions will develop innovative therapies targeting treatment resistant human cancers.
Requirements: Basic histological and biochemical knowledge is required.
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