Wei Hsu, Ph.D.

We are interested in the mechanisms that support embryonic morphogenesis, tissue homeostasis and disease pathogenesis. Focusing on Wnt as one of the most prevalent signaling pathways in developmental biology, we are establishing how Wnt signaling and its crosstalk with other pathways control pluripotency and differentiation in stem cells, and homeostasis in mature cells. We are also interested in the epigenetic and post-translation regulations causative to human diseases. Our goal is to use this basic knowledge to develop innovative strategies for disease prevention and therapy.

Current projects:
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, fate determination and differentiation of skeletal stem cells, cell adhesion and interaction, 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 regulatory networks, we hope to advance the knowledge base of skeletal diseases.
2. Stem Cell Biology and Regenerative Medicine
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 the 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. A similar human stem cell population has also been identified and their reparative and regenerative potential are being examined. In addition, we are interested in the survival and development of neural stem cells regulated by the SUMO pathway. By enhancing our understanding of stem cells, we are closer to translating our findings for clinical use, improving reconstructive surgical repair, and maximizing the benefits of regenerative medicine.
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 SENP2 in the survival and development of tissue-specific stem cells and niches. Current efforts focus on identifying its targets and downstream effects on the SUMO regulatory pathway in development and maintenance of the craniofacial and body skeletons, and neural development and degeneration, e.g. Alzheimer's Disease, Huntington's Disease, and 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 regulatory mechanisms underlying the making of Wnt and its cellular signaling in signal-producing and signal-receiving cells, respectively. The main focus is to investigate our discovery of Gpr177/ Wntless as a master regulator of Wnt trafficking in the secretory and retrograde pathways. We study the Gpr177-mediated regulation of Wnt in the development of various organs, birth defects, and cancers.
5. Epigenetic Regulation
This new initiative 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 and a few other novel miRNAs we identified in craniofacial development and disease, skeletal remodeling and osteoporosis.