Xingbin Ai, Ph.D.
Research Scientist
Heparan sulfate, endosulfatase, tumor progression, stem cell specification
Email: xingbina at bbri.org

Research Summary
Both embryonic development and stem cell self-renewal and regeneration are controlled by a number of extracellular signals. These signals, including Wnts, BMP, FGFs, GDNF and VEGF, interact with heparan sulfate (HS) in the extracellular matrix for distribution and transmission. My major research interest is to investigate how HS 6-O-endosulfatases, Sulf1 & Sulf2, regulate these extracellular signaling by controlling sulfated HS sequences in embryos and adult stem cells using a combination of biochemical, cell biological and genetic approaches. We have demonstrated that Sulfs are required for embryonic esophageal innervation by their differential expression in esophageal muscle and in enteric progenitors, respectively, and by their regulation of both GDNF distribution and reception in the embryonic esophagi (Fig. A). Sulfs are also required for myogenic differentiation during skeletal muscle regeneration by repressing FGF and HGF signaling in satellite cells (Fig. B). In addition, Sulfs play essential roles during skin wound healing. Our results have demonstrated differential functions of Sulfs in extracellular signaling. Ongoing studies investigate additional defects in Sulf1-/-;Sulf2-/- embryos and adult stem cells.

Selected Publications
Langsdorf A, Do AT, Kusche-Gullberg M, Emerson CP Jr, Ai X. Sulfs are regulators of growth factor signaling for satellite cell differentiation and muscle regeneration. Dev Biol. 2007;311(2):464-77.

Ai X, Kitazawa T, Do AT, Kusche-Gullberg M, Labosky PA, Emerson CP Jr. SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation. Development. 2007;134(18):3327-38.

Danesin C, Agius E, Escalas N, Ai X, Emerson C, Cochard P, Soula C. Ventral neural progenitors switch toward an oligodendroglial fate in response to increased Sonic hedgehog (Shh) activity: involvement of Sulfatase 1 in modulating Shh signaling in the ventral spinal cord. J Neurosci. 2006;26(19):5037-48.

Wang S, Ai X, Freeman SD, Pownall ME, Lu Q, Kessler DS, Emerson CP Jr. QSulf1, a heparan sulfate 6-O-endosulfatase, inhibits fibroblast growth factor signaling in mesoderm induction and angiogenesis. Proc Natl Acad Sci U S A. 2004;101(14):4833-8.

Ai X, Do AT, Lozynska O, Kusche-Gullberg M, Lindahl U, Emerson CP Jr.  QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling. J Cell Biol. 2003;162(2):341-51.

Dhoot GK, Gustafsson MK, Ai X, Sun W, Standiford DM, Emerson CP Jr.  Regulation of Wnt signaling and embryo patterning by an extracellular sulfatase. Science. 2001;293(5535):1663-6.

PubMed:
Click here for a list of publications (searches the National Library of Medicine's PubMed database.)