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.
2014 Oct 1
Sakamori R, Yu S, Zhang X, Hoffman A, Sun J, Das S, Vedula P, Li G, Fu J, Walker F, Yang CS, Yi Z, Hsu W, Yu DH, Shen L, Rodriguez AJ, Taketo MM, Bonder EM, Verzi MP, Gao N. "CDC42 Inhibition Suppresses Progression of Incipient Intestinal Tumors." Cancer research. 2014 Oct 1; 74(19):5480-92. Epub 2014 Aug 11.
Fu J, Yu HM, Chiu SY, Mirando AJ, Maruyama EO, Cheng JG, Hsu W. "Disruption of SUMO-Specific Protease 2 Induces Mitochondria Mediated Neurodegeneration." PLoS genetics. 2014 Oct; 10(10):e1004579. Epub 2014 Oct 09.
McGee-Lawrence ME, Carpio LR, Bradley EW, Dudakovic A, Lian JB, van Wijnen AJ, Kakar S, Hsu W, Westendorf JJ. "Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice." Bone. 2014 Sep; 66:277-86. Epub 2014 Jun 25.
Li TF, Yukata K, Yin G, Sheu T, Maruyama T, Jonason JH, Hsu W, Zhang X, Xiao G, Konttinen YT, Chen D, O'Keefe RJ. "BMP-2 induces ATF4 phosphorylation in chondrocytes through a COX-2/PGE2 dependent signaling pathway." Osteoarthritis and cartilage. 2014 Mar; 22(3):481-9. Epub 2014 Jan 11.
Xiao-Jing Zhu, YuDong Liu, Zhong-Min Dai, Xiaoyun Zhang, XueQin Yang, Yang Li, Mengsheng Qiu, Jiang Fu, Wei Hsu, YiPing Chen and Zunyi Zhang. "BMP-FGF signaling axis mediates Wnt-induced epidermal stratification in developing mammalian skin". PLOS Genetics (In Press). 2014; .