Wei Hsu, Ph.D.

Research Program: Morphogenetic Signaling Network in Development and Disease
1. Skeletogenic Signaling Pathways in Development and Deformity
The primary objective is to investigate the fundamental mechanisms underlying skeletogenesis, including the development of skeletogenic mesenchyme, cell fate determination and differentiation of skeletal stem cells, intramembranous and endochondral ossifications, development of TMJ, and tooth morphogenesis. We currently focus on the interplay of Wnt, FGF and BMP pathways. By elucidating the mechanism underlying skeletal development mediated by these genetic regulatory networks, we hope to advance the knowledge base of skeletal diseases.
2. Stem Cell Biology
This is an integral part of our projects studying the genetic control of cellular signals and signal transduction mechanisms underlying the development of lineage-specific stem cells and niches in development and disease. We currently focus on characterization of a newly identified and isolated population of skeletal stem cells with long-term self-renewal and differentiating and regenerative abilities, contributing directly to tissue repair by replacing the damaged skeleton. In addition, we are interested in survival and development of neural stem cells regulated by the SUMO pathway.
3. Ubiquitin-like Modifiers
A multi-disciplinary approach is used to study the SUMO (small ubiquitin-related modifier) pathway in mammalian development and disease. We have demonstrated the requirement of SUMO-specific protease 2 in survival and development of tissue-specific stem cells and niches. Current efforts focus on determining the role of SUMO-specific protease 2, identifying its targets and downstream effects on the SUMO regulatory pathway in skeletal development and remodeling, as well as neural development and degeneration, e.g. Alzheimer's Disease, Huntington's Disease, optic neuropathies. The long-term goal is to gain important insight into the SUMO regulatory pathway and to explore preventive and therapeutic applications.
4. Wnt Signal Production and Transduction
This project deciphers the regulatory mechanism underlying the making of Wnt and its signal transduction in signal-producing and signal-receiving cells, respectively. The main focus is to investigate our discovery of Gpr177/mouse Wntless as a master regulator for intracellular trafficking of Wnt. We currently investigate the Gpr177-mediated regulation of Wnt in the development of various organs, birth defects, and cancers.
5. Epigenetic regulation
The main focus is to elucidate the mechanisms by which microRNAs regulate the development and homeostasis of the craniofacial and body skeletons. We are particularly interested in the role of miR-23a cluster in bone remodeling and osteoporosis.