Genetic Regulatory Circuits in Development and Disease
1. Craniofacial Morphogenesis
The primary objective is to investigate the fundamental mechanisms underlying craniofacial skeletogenesis, including development of cranial neural crest, tooth development, palatogenesis and calvarial morphogenesis. We currently focus on the interplay of Wnt, FGF and BMP pathways essential for expansion, cell fate determination and differentiation of the skeletal precursors. By elucidating these genetic regulatory networks, we hope to advance the knowledge base of skeletal deformities.
2. Breast Development and Cancer
The main focus is to elucidate the mechanisms by which Wnt signaling regulates stem/progenitor cells at different phases of breast development and their involvements in malignant transformation. We are particularly interested in the role of these precursor cells during parity-mediated remodeling of the mammary gland. Our current efforts focus on the role of mammary stem cells in development and cancer.
3. Stem Cell Biology
This is an integral part of our projects studying the genetic control of cellular signals and signal transduction mechanisms underlying development of lineage-specific stem cells/progenitors in skeletal, nervous and reproductive systems.
4. Ubiquitin-like Modifiers
A multi-disciplinary approach is used to study the SUMO (small ubiquitin-related modifier) pathway in mammalian development and disease. We are determining the role of SUMO-specific protease 2 in placental insufficiencies, cardiovascular, skeletal and neurological disorders, and cancers.
5. Wnt Production and Signaling
This project deciphers the regulatory mechanism underlying the making of Wnt and its signaling effects in signal-producing and signal-receiving cells. The main focus is to test our hypothesis that the newly identified Gpr177/mouse Wntless is a master regulator for intracellular trafficking of Wnt. We currently investigate the reciprocal regulation of Wnt and Gpr177 in craniofacial, skeletal, skin, tooth and mammary development, as well as the Gpr177-mediated regulation of Wnt in birth defects and cancers.
Jiang M, Ku WY, Fu J, Offermanns S, Hsu W, Que J. "Gpr177 regulates pulmonary vasculature development." Development.. 2013 Sep; 140(17):3589-94. Epub 2013 Jul 24.
Maruyama T, Jiang M, Hsu W. "Gpr177, a novel locus for bone mineral density and osteoporosis, regulates osteogenesis and chondrogenesis in skeletal development." Journal of bone and mineral research : the official journal of the
American Society for Bone and Mineral Research. 2013 May; 28(5):1150-9.
2013 Apr 26
Zhu X, Zhao P, Liu Y, Zhang X, Fu J, Yu HM, Qiu M, Chen Y, Hsu W, Zhang Z. "Intra-epithelial requirement of canonical Wnt signaling for tooth morphogenesis." The Journal of biological chemistry.. 2013 Apr 26; 288(17):12080-9. Epub 2013 Mar 24.
Fu J, Hsu W. "Epidermal Wnt controls hair follicle induction by orchestrating dynamic signaling crosstalk between the epidermis and dermis." The Journal of investigative dermatology.. 2013 Apr; 133(4):890-8. Epub 2012 Nov 29.
2013 Feb 22
McGee-Lawrence ME, Li X, Bledsoe KL, Wu H, Hawse JR, Subramaniam M, Razidlo DF, Stensgard BA, Stein GS, van Wijnen AJ, Lian JB, Hsu W, Westendorf JJ. "Runx2 protein represses Axin2 expression in osteoblasts and is required for craniosynostosis in Axin2-deficient mice." The Journal of biological chemistry.. 2013 Feb 22; 288(8):5291-302. Epub 2013 Jan 07.