Our long-term goal is to provide novel therapeutic cues to treat malignant cancer, immune disorders, and infectious diseases. We are especially interested in exploring roles of glycoconjugates and their modifying enzymes in the pathogenesis, also mining small molecules and antibodies having therapeutic effects on the diseases.
Glycoconjugates are one of the major constituents in mammalian body, however, roles of those molecules in the biological processes have not been fully uncovered. Sulfated glycoconjugates heparan sulfate and heparin interact with many kinds of functional molecules such as extracellular matrix proteins, enzymes, cytokines/chemokines and viral proteins, thereby participate in our homeostatic and disease processes. Expression and distribution of the glycoconjugates are metabolically regulated by modifying enzymes including heparanase, the only known mammalian endoglycosidase that cleaves heparan sulfate side chains of proteoglycans.
Heparanase has been named by our collaborators Drs Motowo Nakajima, Tatsuro Irimura and Garth Nicolson in 1983, derived from heparan sulfate degrading activity in metastatic melanoma cells. The enzyme regulates the structure and function of heparan sulfate proteoglycans and remodeling cell surfaces and the extracellular matrices. Although there have been accumulating evidence supporting that heparanase is a key molecule to drive cancer malignancy and inflammatory diseases, our current knowledge is limited to understanding how the degradation process is regulated and what follows the degradation. Exploring how heparanase modulates pathological changes occurring in cancer progression and immune disorders, we devote our efforts to make a major breakthrough in glycoscience and pharmaceutical sciences.
- invasive mechanism of metastatic cancer and inflammatory cells through 3D tissues and extracellular matrices
- biological roles of mast cell granular materials in immunity and allergy
- involvement of cytokine-like activity of heparanase in cancer biology
- cleavage of carbohydrates as an alert of danger
Katsuhiko TAKAHASHI
● research interests
- biology of pin1 (peptidyl-prolyl cis-trans isomerase)
- developmental changes in placenta
- adipocyte differentiation
- osteoporosis
- cell cycle regulation of cancer cells via cyclin kinase inhibitors
