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  4. Yoshitasu Sei, M.D., Ph.D.

Yoshitasu Sei, M.D., Ph.D.

Scientific Focus Areas: Cancer Biology, Cell Biology, Computational Biology, Molecular Biology and Biochemistry, Stem Cell Biology

Professional Experience

  • Ph.D., Kurume University School of Medicine, Japan, 1988
  • M.D., Kurume University School of Medicine, Japan, 1983

Research Goal

Our goal is to understand cellular and molecular biological mechanisms of differentiation and tumorigenesis of enteroendocrine cells.

Current Research

Our research focuses on investigating cellular and molecular biological mechanisms of differentiation and tumorigenesis of enteroendocrine cells. We mainly use transgenic mouse models and the ex-vivo organoid system for the investigations. We have recently identified a novel subset of enteroendocrine cells that express stem cell markers Lgr5, CD133, and DCAMKL1 at the crypt base in the intestine. Unlike the majority of enteroendocrine cells that differentiate and migrate up to the villi, this subset expresses both stem and mature endocrine markers. By tracing GFP+ cells in the organoid system, we found that this subset appears around the +4 position in the crypt and migrates down to the crypt base where intestinal stem cells reside between the Paneth cells. The aims of our investigations are to find 1) what specific physiological function and property this subset of enteroendocrine cells possess compared with the cells that differentiate with upward migration, and 2) if these stem marker-expressing enteroendocrine cells, which reside where Wnt signaling is constantly active, are susceptible to the tumorigenesis.

Applying our Research

The research on endocrine cells in the intestine has been subjected to potential new drug discoveries and therapeutics for diseases widely affecting public health including obesity, diabetes, and digestive diseases such as irritable bowel syndrome and neuroendocrine tumors.

Need for Further Study

Further studies are needed to understand how cell molecular signaling and chromosome remodeling cooperate to regulate cell fate and differentiation.

Select Publications

Asymmetric Cell Division-Dominant Neutral Drift Model for Normal Intestinal Stem Cell Homeostasis.
Sei Y, Feng J, Chow CC, Wank SA.
Am J Physiol Gastrointest Liver Physiol (2018 Oct 25) Abstract/Full Text
Mature enteroendocrine cells contribute to basal and pathological stem cell dynamics in the small intestine.
Sei Y, Feng J, Samsel L, White A, Zhao X, Yun S, Citrin D, McCoy JP, Sundaresan S, Hayes MM, Merchant JL, Leiter A, Wank SA.
Am J Physiol Gastrointest Liver Physiol (2018 Oct 1) 315:G495-G510. Abstract/Full Text
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Research in Plain Language

Our research focuses on studying hormone-producing cells in the intestine. Hormone-producing cells (enteroendocrine cells) produce hormones by sensing chemicals used to regulate physiological functions in the digestive system. We use genetically engineered mouse models and a gut model in the culture dish to study how the enteroendocrine cells differentiate from intestinal stem cells to mature hormone producing cells. Recently, we discovered a group of enteroendocrine cells that express stem cell markers and stay in the stem cell area. We think this group of enteroendocrine cells may have a unique capability in terms of stemness in certain conditions and that this group of cells may be responsible for the generation of enteroendocrine tumors, including carcinoids. Studying this group of cells may help scientists discover how endocrine tumors are generated and therefore help them create new drugs to treat these tumors.

Research Images