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Related Research Units

Intellectual and Developmental Disabilities Research Center Research
Neurology Research
He Laboratory Research
F.M. Kirby Neurobiology Center

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. 

Research Background

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 Chemistry, Journal 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.

Publications

  1. Overlapping peri-implantation phenotypes of ZNHIT1 and ZNHIT2 despite distinct functions during early mouse development†. Biol Reprod. 2024 Nov 11; 111(5):1017-1029. View Abstract
  2. TATA-binding associated factors have distinct roles during early mammalian development. Dev Biol. 2024 07; 511:53-62. View Abstract
  3. The role of Wnt signaling in Xenopus neural induction. Curr Top Dev Biol. 2023; 153:229-254. View Abstract
  4. Single-molecule dynamics of Dishevelled at the plasma membrane and Wnt pathway activation. Proc Natl Acad Sci U S A. 2020 07 14; 117(28):16690-16701. View Abstract
  5. APC Deficiency Leads to ß-Catenin Stabilization and Signaling Independent of LRP5/6. Dev Cell. 2019 06 17; 49(6):825-826. View Abstract
  6. Methods for Studying Wnt Protein Modifications/Inactivations by Extracellular Enzymes, Tiki and Notum. Methods Mol Biol. 2016; 1481:29-38. View Abstract
  7. Characterization of Tiki, a New Family of Wnt-specific Metalloproteases. J Biol Chem. 2016 Jan 29; 291(5):2435-43. View Abstract
  8. Notum is required for neural and head induction via Wnt deacylation, oxidation, and inactivation. Dev Cell. 2015 Mar 23; 32(6):719-30. View Abstract
  9. Disulfide bond requirements for active Wnt ligands. J Biol Chem. 2014 Jun 27; 289(26):18122-36. View Abstract
  10. Quantitative evaluation of the performance of an industrial benchtop enclosing hood. J Occup Environ Hyg. 2013; 10(8):409-18. View Abstract
  11. Unwinding a path to nuclear beta-catenin. Cell. 2006 Oct 06; 127(1):40-2. View Abstract
  12. A WNTer wonderland in Snowbird. Development. 2006 Jul; 133(14):2597-603. View Abstract
  13. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development. 2004 Apr; 131(8):1663-77. View Abstract

Contact Xi He

Phone: 617-919-2257
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