Dr.  Kai Lei received his Bachelor’s Degree from Wuhan University and Ph.D. in  Developmental Biology at the Institute of Developmental Biology and Molecular  Medicine of Fudan University. He then became a postdoctoral research associate  with Dr. Sánchez Alvarado at Stowers Institute for Medical Research. Dr. Kai Lei  will join the faculties in the School of Life Sciences of Westlake University in  October 2018. His lab studies the molecular mechanism of adult stem cell  repopulation and tissue regeneration.

Therapies  facilitating the regeneration of tissues lost to injury or aging is one of the  greatest unmet needs facing the medical community today. A major obstacle to the  development of robust regenerative therapies has been a fundamental deficiency  in our understanding of the complex molecular mechanisms regulating  regeneration.

To  help address this knowledge gap, our laboratory studies the molecular mechanisms  underpinning regeneration that have evolved across the animal kingdom. Using  both invertebrate and vertebrate research organisms—along with state-of-the-art  tools in genetics, cell biology, biochemistry, bioinformatics, and  high-throughput technologies—we aim to elucidate conserved and divergent  mechanisms regulating adult stem cell biology. The ultimate goal of our research  is to identify general principles of regeneration and molecular factors that  could aid the development of future therapies in humans.

One  invertebrate model system we employ is the planarian flatworm. Planarians can  fully regenerate a new individual from a piece of tissue as small as  1/279^th the size of the original animal. This amazing regenerative  capacity is due to the fact that planarians possess a subset of stem cells  called cNeoblasts: one of the only pluripotent adult stem cells known to  naturally occur in the animal kingdom. A single cNeoblast can completely  regenerate all cell types in the planarian’s body, including the entire adult  stem cell population itself.

Previously,  we used a candidate approach to systematically analyze the function of  extracellular signaling pathways during the reconstitution of the adult stem  cell compartment from cNeoblasts following sublethal irradiation. We identified  EGF signaling as a key regulator in this process. Furthermore, we demonstrated  the requirement of asymmetric stem cell division in planarians for the first  time (Developmental Cell, 2016).

Based  on these studies, we aim to use the EGF phenotype as a “molecular foothold” for  further expanding our understanding of planarian adult stem cell regulation.  Furthermore, this research will inform concurrent studies of regeneration in  mice aimed at distinguishing mechanisms regulating adult stem cell biology that  are conserved versus divergent between invertebrates and vertebrates.

1. Niu K., Xu H., Xiong Z.Y., Zhao Y., Gao C., Seidel W. C., Pan X., Ying Y., Lei K. Canonical and early lineage-specific stem cell types identified in planarian SirNeoblasts. Cell Regeneration, 2021, 10(15).

2. Yang, Z.^#, Li, L.^#, Ling, J., Liu, T., Huang, X., Ying, Y., Zhao, Y., Zhao, Y., Lei, K.*, Chen, L.*, Chen, Z.* Cyclooctatetraene-conjugated cyanine mitochondrial probes minimize phototoxicity in fluorescence and nanoscopic imaging. Chem. Sci. 2020, 11:8506-8516. (* co-corresponding authors; # co-first authors)

3. Lei, K., McKinney S., Ross E., Lee H.C., Sánchez Alvarado A. Cultured pluripotent planarian stem cells retain potency and express proteins from exogenously introduced mRNAs. BioRxiv. March 12, 2019.

4. Davies, E., Lei, K., Seidel, C., Kroesen, A., McKinney, S., Guo, L., Robb S., Ross, E., Gotting, K., Sánchez Alvarado, A. (2017) Embryonic origin of adult stem cells required for tissue homeostasis and regeneration. eLife. 6:e21052.

5. Lei, K.*, Vu H., Mohan R., McKinney S., Seidel C., Alexander R., Gotting K., Workman J., Sánchez Alvarado A.* (2016) Egf signaling directs neoblast repopulation by regulating asymmetric cell division in planarians. Developmental Cell. 38(4):413-29. (* co-corresponding authors)

6. Lei, K., Zhu, X., Xu, R., Xu, T., Zhuang, Y., Han, M. (2012) Inner nuclear envelope proteins SUN1 and SUN2 play a prominent role in the DNA damage response. Current Biology. 22(17):1609-15.

7. Yu, J.^#, Lei, K.^#, Zhou, M., Craft, C., Xu, G., Xu, T., Zhuang, Y., Xu, R., Han, M. (2011) KASH protein Syne-2/Nesprin-2 and SUN proteins SUN1/2 mediate nuclear migration during mammalian retinal development. Human Molecular Genetics. 20(6):1061-73. (# co-first authors)

8. Zhang, X, Lei, K., Yuan, X., Wu, X., Zhuang, Y., Xu, T., Xu, R., Han, M. (2009) SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice. Neuron. 64(2):173-87.

9. Lei, K.^#, Zhang, X.^#, Ding, X., Guo, X., Chen, M., Zhu, B., Xu, T., Zhuang, Y., Xu, R., Han, M. (2009) SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice. Proc. Natl. Acad. Sci. U. S. A. 106(25): 10207–12. (# co-first authors)

Complete list of publications: https://scholar.google.com/citations?user=5dRiqSgAAAAJ&hl=en

lei_lab@westlake.edu.cn

leikai@westlake.edu.cn