Shuo Wei, Ph.D.


Fall: BISC401/609 Molecular Biology of the Cell

Spring: BISC467/667 Current Topics in Development and Cancer

Research Interests

The Wei lab is interested in the regulation of cell signaling by metalloproteinases and other proteins in development and disease.

Current Projects

Project 1. PI3K/Akt signaling in cranial neural crest (CNC) development. The CNC cells are multipotent stem cells that give rise to many craniofacial structures in vertebrates. Perturbations in CNC development can cause craniofacial defects such as cleft lip/palate, which are some of the most common birth defects in humans. The PI3K/Akt pathway is required for early induction of the CNC lineage during vertebrate embryogenesis. Using the Western clawed frog Xenopus tropicalis as a model, we identified several genes that are potential upstream regulators or downstream effectors of the PI3K/Akt pathway in CNC induction. Importantly, recent clinical reports have linked mutations in these genes to human craniofacial defects. We are actively investigating the roles of these genes in PI3K/Akt signaling and CNC induction.

Project 2. Regulation of canonical Wnt signaling by disintegrin metalloproteinases (ADAMs) in development and cancer. The canonical Wnt pathway plays important roles in many developmental and pathological processes, including CNC induction, carcinogenesis and tumor progression. ADAMs are transmembrane proteases that regulate cell signaling through their proteolytic and non-proteolytic activities. We found that the activation of canonical Wnt signaling during CNC induction and tumor progression depends on several ADAM proteases. These ADAMs can cleave key components or regulators of the canonical Wnt pathway, resulting in Wnt activation. Current efforts are focused on understanding the mechanisms of action for these ADAMs in canonical Wnt signaling, as well as generating small-molecule and peptidic ADAM inhibitors for therapeutic purposes.

Project 3. Intracellular trafficking, maturation and turnover of metalloproteinases. Mutations in genes encoding certain ADAMs and other metalloproteinases have been associated with diseases such as tumors, arthritis and neurodegenerative diseases. Interestingly, many of these mutations affect the trafficking, maturation and turnover of metalloproteinases. We have uncovered two novel mechanisms for the maturation and turnover of metalloproteinases, respectively, and both mechanisms are related to intracellular trafficking of these metalloproteinases. We are continuing to study the basic biochemistry and cell biology of these processes, and to develop new means to manipulate these processes as potential therapy.

Research Group

  • Pathirennehelage (“Chamath”) Chandrasekera – Graduate student (B.S., Baylor University)
  • Andrew Connell - Graduate student (B.A., University of Delaware)
  • Effie Halakos - Graduate student (co-mentored with Dr. Robert Mason, Nemours Children's Hospital)
  • Congyu Lu – Graduate student (M.S., Northwest A&F University, China)
  • Mark Perfetto – Graduate student (B.S., West Virginia University)
  • Xiaolu Xu - Graduate student (B.S., Shandong University, China)
  • Sherly Basil - Undergraduate student
  • Pallavi Kulkarni - Undergraduate student

Selected Publications

  • Li, J., Perfetto, M., Neuner, R., Bahudhanapati, H., Christian, L., Mathavan, K., Bridges, L.C., Alfandari, D., and Wei, S. (2018) Xenopus ADAM19 regulates Wnt signaling and neural crest specification by stabilizing ADAM13. Development 145, dev158154.  Equal contributors.
  • Wang, J., Koganti, P., Yao, J., Wei, S., and Cleveland, B. (2017) Comprehensive analysis of lncRNAs and mRNAs in skeletal muscle of rainbow trout (Oncorhynchus mykiss) exposed to estradiol. Sci. Rep. 7, 11780.
  • Li, J., Qu, J., Shi, Y., Perfetto, M., Ping, Z., Christian, L., Niu, H., Mei, S., Zhang, Q, Yang, X. and Wei, S. (2017) Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation. Sci. Rep. 7, 43173.
  • Fu, L., Zhang, M., Mastrantoni, K., Perfetto, M., Wei, S. and Yao, J. (2016) Bovine Lhx8, a germ cell-specific nuclear factor, interacts with Figla. PLoS One 11, e0164671.
  • Bahudhanapati, H., Bhattacharya, S., and Wei, S. (2015) Evolution of vertebrate Adam genes; duplication of testicular Adams from ancient Adam9/9-like loci. PLoS One 10, e0136281.
  • Christian, L., Bahudhanapati, H., and Wei, S. (2013) Extracellular metalloproteinases in neural crest development and craniofacial morphogenesis. Crit. Rev. Biochem. Mol. Biol. 48, 544-560.
  • Wei, S. (2013) ADAM metalloproteinases. In The Handbook of Proteolytic Enzymes, 3rd edition. Edited by: Rawlings, N.D. and Guy, S. Oxford: Academic Press, 1086-1094.
  • Xu, G., Wei, S., White, J.M., and DeSimone, D.W. (2012) Identification and characterization of ADAM41, a novel metalloproteinase in Xenopus. Int. J. Dev. Biol. 56, 333-339.
  • Wei, S., Xu, G., Bridges, L.C., Williams, P., Nakayama, T., Shah, A., Grainger, R.M., White, J.M., and DeSimone, D.W. (2012) Roles of ADAM13-regulated Wnt activity in early Xenopus eye development. Dev. Biol. 363, 147-154.
  • Wu, Y., Wei, S., Van Doren, S.R., and Brew, K. (2011) Entropy increases from different sources support the high-affinity binding of the N-terminal inhibitory domains of tissue inhibitors of metalloproteinases (N-TIMPs) to the catalytic domains of matrix metalloproteinases (MMPs) -1 and-3. J. Biol. Chem. 286, 16891-16899.
  • Wei, S., Xu, G., Bridges, L.C., Williams, P., White, J.M., and DeSimone, D.W. (2010) ADAM13 induces cranial neural crest by cleaving class B ephrins and regulating Wnt signaling. Dev. Cell 19: 345-352.
  • Wei, S., Whittaker, C., Xu, G., Bridges, L.C., Shah, A., White, J.M., and DeSimone, D.W. (2010) Conservation and divergence of ADAM family proteins in the Xenopus genome. BMC Evol. Biol. 10: 211.
  • Van Doren, S.R., Wei, S., Gao, G., Dague, B.B., Palmier, M.O., Bahudhanapati, H., and Brew, K. (2008) Inactivation of N-TIMP-1 by N-terminal acetylation when expressed in Bacteria. Biopolymers 89: 960-968.
  • Hamze A.B., Wei, S., Bahudhanapati, H., Kota, S., Acharya, K.R., and Brew, K. (2007) Constraining specificity in the N-domain of tissue inhibitor of metalloproteinases-1; gelatinase-selective inhibitors. Protein Sci. 16: 1905-1913. Equal contributors.
  • Lauer-Fields, J.L., Cudic, M., Wei, S., Mari, F., Fields, G.B., and Brew, K. (2007) Engineered sarafotoxins as TIMP-like MMP inhibitors. J. Biol. Chem. 282: 26948-26955.
  • Iyer, S., Wei, S., Brew, K., and Acharya, K.R. (2007) Crystal structure of the catalytic domain of matrix metalloproteinase-1 in complex with the inhibitory domain of tissue inhibitor of metalloproteinase-1. J. Biol. Chem. 282: 364-371.
  • Wei, S., Kashiwagi, M., Kota, S., Xie, Z., Nagase, H., and Brew, K. (2005) Reactive site mutations in TIMP-3 disrupt inhibition of MMPs but not ADAM-17 (TACE). J. Biol. Chem. 280: 32877-32882.
  • Cui, T., Wei, S., Brew, K., and Leng, F. (2005) Energetics of binding the mammalian high mobility group protein HMGA2 to poly(dA-dT)2 and poly(dA)poly(dT). J. Mol. Biol. 352: 629-645.
  • Wei, S., Xie, Z., Filenova, E., and Brew, K. (2003) Drosophila TIMP is a potent inhibitor of MMPs and TACE: similarities in structure and function to TIMP-3. Biochemistry 42: 12200-12207.
  • Wei, S., Chen, Y., Chung, L., Nagase, H., and Brew, K. (2003) Protein engineering of the tissue inhibitor of metalloproteinase 1 (TIMP-1) inhibitory domain. In search of selective matrix metalloproteinase inhibitors. J. Biol. Chem. 278: 9831-9834.

Assistant Professor

Phone: (302) 831-1146


Office: 235 Wolf Hall

Lab: 259 Wolf Hall


  • B.S., University of Science and Technology of China
  • Ph.D., University of Miami Miller School of Medicine
  • Postdoc: University of Virginia