Year in Program: 5th
Hometown: Taiyuan, China
Mentors: Drs. Hong and Zhang
My interests are determining the roles of circadian rhythms in: 1. regeneration of intestinal stem cells (ISCs) via mTOR signaling, and 2. cell proliferation and tumor development via regulation of Wnt, p53 and Apc.
1. Mammalian Target of Rapamycin Complex 1 (mTORC1) is the central core of anabolic metabolism, by surrounding hormone and growth factor signal to direct synthesis of macromolecules, including DNA, ribosome (rRNA and protein) and lipid. Previous studies showed that mTORC1 is fundamental in ISC maintenance and is increased upon Bmal1 disruption both in vivo and in mouse lung fibroblast. Other publications showed that general inhibition of mTORC1 is not sufficient in cancer therapy, so that deeper study downstream of mTORC1 signaling and temporal inhibition is required. However, the role of circadian rhythms in ISC regeneration via mTOR signaling remains unknown.
Circadian rhythms strongly influence intestinal crypt physiology, including cell cycle, cell proliferation, and ISC regeneration. For cell cycle, a few of the molecular connections of intracellular coupling were uncovered, and our group recently identified a mechanism of circadian rhythm and cell cycle coupling that expanded to the intercellular level via Wnt signaling between Paneth cells and ISCs (Matsu-Ura, T. et al.). In addition, the key components of proliferation (e.g. Wnt, Kras, c-Myc, Apc) show circadian rhythms, and previous reports showed that overexpression of circadian genes (e.g. Bmal1) increases the efficiency of chemotherapy in cancer treatment, which indicates that circadian rhythm is highly associated with cell proliferation and tumor development. However the molecular mechanisms connecting circadian rhythm with cell cycle, cell proliferation, and tumor development remain largely unknown.
Interests after work: cooking, painting, and traveling