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Xi He
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Xi He, PhD

Department: Neurology
Research Centers: F.M. Kirby Neurobiology Center
Hospital Title: Research Associate
Academic Title: Professor of Neurology, Harvard Medical School
Research Area: Cell-cell communication
early nervous system development
Wnt family of secreted morphogens and signaling
cancer
skeletal and neurologic diseases

Contact:

617-919-2257

Research Overview

Double-headed frogs

Manipulation of Wnt signaling causes frog embryos to develop with two heads and nervous systems, as revealed by neural-specific staining.  This experiment demonstrates the critical role of Wnt signaling in the development of vertebrate embryos.

My laboratory seeks to understand the molecular basis of cell-to-cell communication, and how this communication regulates embryonic and neural development in vertebrates. We are also interested in learning how defective regulation of cell communication causes human cancers and diseases. In particular, we are investigating signaling mechanisms employed by secreted growth factors of the Wnt family, which play critical roles in establishing the anterior-posterior axis of the embryo and underlie the formation of head versus trunk regions during early embryogenesis. Wnt signaling pathways are also pivotal in the development of human cancers--as several key Wnt signaling components are encoded by human oncogenes or tumor suppressor genes--and in the pathogenesis of many human diseases, such as osteoporosis and degenerative disorders.

We aim to identify molecular components of Wnt signaling pathways and the mechanisms by which Wnt pathways are activated and governed during embryonic development and human tumorigenesis. Over the past decade, we have identified a number of key molecules in Wnt signaling, including kinases and transmembrane receptor components, and elucidated their mechanisms of action in signal transduction. We have also identified or elucidated various important Wnt signaling regulators and their critical functions in head formation, as well as in human skeletal diseases. We carry out our research in frog embryos and genetically engineered mice.

We are also beginning to explore chemical manipulation of Wnt signaling pathways, with the long-term goal of therapeutically targeting Wnt signaling for potential treatment of human cancer and other diseases. 

About Xi He

Xi He received his PhD in 1992 from the University of California, San Diego, where he worked in the laboratory of Michael G. Rosenfeld. He completed a postdoctoral fellowship in 1996 at the National Institutes of Health, under the supervision of Harold E. Varmus. He was a Pew Scholar in Biomedical Sciences, a Klingenstein Fellow in Neuroscience, a Keck Foundation Distinguished Young Scholar in Medical Research and a Leukemia and Lymphoma Society Scholar. He is a Chang Jiang Guest Professor at the School of Life Science and Technology, Huazhong University of Science and Technology in Wuhan, China, inducted by the Ministry of Education of China.

Xi He is a member of the executive board of the Stem Cell Program at Boston Children's Hospital and a member of the editorial boards of Journal of Biological ChemistryJournal of Genetics and Genomics and Protein & Cell. He has served and is serving on the Scientific Advisory Boards of institutes of the Chinese Academy of Sciences and of biotechnology companies in the United States, China and Europe.

Key Publications

  • MacDonald B, Tamai K, and He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 2009; 17:9-26.

  • Zeng X, Tamai K, Doble B, Li S, Huang H, Habas R, Okamura H, Woodgett J and He X. A dual-kinase mechanism for Wnt coreceptor phosphorylation and activation. Nature 2005; 438:873-77.

  • Tamai K, Zeng X, Chunming L, Zhang X, Harada Y, Chang Z, He X. A mechanism for Wnt coreceptor activation. Molecular Cell 2004; 13:149-56.

  • Liu C, Li Y, Semenov M, Baeg G-H, Han C, Tan Y, Zhang Z, Lin X, He X. Control of beta-catenin phosphorylation-degradation by a dual-kinase mechanism. Cell 2002; 108:837-47.

  • Semenov MV, Tamai K, Brott BK, Kuhl M, Sokol S, He X. The Wnt antagonist Dickkopf 1 is a ligand for low density lipoprotein receptor related proteins. Curr Biol 2001; 26:951-61.

  • Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet J-P, He X. LDL receptor-related proteins in Wnt signal transduction. Nature 2000; 407: 530-35.

For a list of Xi He's publications on PubMed, click here.

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