Research Interests

Metalloproteinases; neural crest

Research Area

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.

Current Members

Wei, Shuo (Principal Investigator/Director)

Contact

Institution: University of Delaware

Address:
Dept of Biological Sciences
University of Delaware
Newark, DE
19716, USA

Web Page: https://www.bio.udel.edu/users/swei

Personal Phone: 304-293-5201 ext. 31540

General/Lab Fax: 304-293-6363