Research Programs

Hakomori Lab

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Sen-itiroh Hakomori, M.D., Ph.D.

Hakomori studies aberrant cell recognition and signaling in cancer based on changes in glycosylation

Dr. Hakomori's scientific career has been devoted to studies on structure, and function of glycosphingolipids (GSLs).

His initial studies were characterization of novel extended lacto-series and globo-series structures, including A1, A2, H, I/i, Lex, Ley, sialyl-Lex, and globo-ABH, some of which were identified as developmentally-regulated or tumor-associated antigens.

His group was the first to identify tumor-associated antigens as GSLs, providing the basis for diagnosis and treatment of human cancer. Additionally, they established the genetic basis of histo-blood group ABO, providing a clear genetic mechanism for deletion or expression of A or B gene.

They have been studying functional roles of GSLs in defining cell adhesion and signal transduction. For example, they were the first to characterize the effect of gangliosides on growth factor receptor function, in terms of inhibitory or promoting effect on receptor-associated tyrosine phosphorylation.

They pioneered the elucidation of GSLs as adhesion molecules based on carbohydrate-to-carbohydrate interaction. This concept was quite novel, and was not well accepted in the cell biological or medical communities in the U.S., since protein-to-protein interaction was generally believed to be the major basis of cell adhesion. However, this concept has been supported increasingly by various other research groups.

Currently, their studies are showing that GSLs or other glycoconjugates, organized in microdomains (termed "glycosynapse"), define cell adhesion coupled with signal transduction.