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Su-Li Cheng, PhD Research Assistant Professor of Medicine
Originally from Tien-Chong, Taiwan, Dr. Cheng received her PhD from the University of Louisville, Louisville, Kentucky, TN. As a postdoctoral student, she worked on the Population Council at Rockefeller University in New York before joining Dr. William A. Peck as a protein biochemist at Washington University in St. Louis. She later worked with Dr. Avioli on signal and integrin transduction. She is currently working with Dr. Dwight A. Towler on the investigation of Wnt signaling as related to vascular calcification. During her career, Dr. Cheng has been awarded the American Society of Bone and Mineral Research Young Investigator's Award along with the Russell S. Fibbs' Basic Science Award and an Outstanding Basic Science Award from the Cervical Spine Research Society. Research Interests Drs Towler and Cheng's research is focused mainly on the roles of Msx2 and canonical Wnt signaling in vascular calcification and bone formation. Vascular calcification is a serious entity in type II diabetes. A diabetic patient with vascular calcification predicts 4-fold increase in amputation rate and 2-fold increase in cardiovascular mortality. They have demonstrated that mice fed with high fat diet develop type II diabetes and vascular calcification. In the vessel walls of mice fed with high fat diet, Msx2 expression is enhanced. Subsequently, they have shown that Msx2 regulates lineage allocation of multipotent mesenchymal cells in favor of osteoblastic cell differentiation at the expense of adipocyte formation. The mechanisms mediating lineage allocation by Msx2 are found to be via suppression of c/EBPa and PPARg2 adipogenic activities and upregulation of canonical Wnt signaling. Msx2 inhibits adipogenesis via protein-protein interaction with c/EBPa, which results in suppressed adipogenic activities of c/EBPa and PPARg2. In addition, Msx2 promotes the expression of canonical Wnts and inhibits the expression of canonical Wnt inhibitor Dkk-1. The canonical Wnt signaling has been shown to suppress adipogenesis but stimulates osteogenesis. The Towler-Cheng team have recapitulated the Msx2 effects in vivo using Msx2 transgenic mice. Msx2 transgenic mice are leaner and have higher bone mineral density. More importantly, the canonical Wnt signaling is activated and calcification detected in aorta and coronary arteries of Msx2 transgenic mice. Thus, Msx2 via canonical Wnt signaling mediates vascular calcification detected in mice fed with high fat diet. The activation of canonical Wnt signaling by Msx2 also increases bone formation. Their future research will be focused on developing a modality to manage vascular calcification without interfering with the integrity of skeleton. Recent Publications Lai C-F and Cheng S-L Signal transductions induced by bone morphogenetic protein-2 and transforming growth factor-b in normal human osteoblastic cells. J Biol Chem 2002; 277:15514-15522. Riew KD, Lou J, Wright NM, Cheng S-L, Bae KT and Avioli LV Thoracoscopic intradiscal spine fusion using a minimally invasive gene therapy technique. J Bone Joint Surg Am 2003; 85-A:866-871. Rifas L and Cheng, S-L IL-13 regulates vascular cell adhesion molecule-1 expression in human osteoblasts. J Cell Biochem 2003; 89:213-219. Cheng S-L, Shao JS, Kachigian N, Loewy AP, and Towler DA Msx2 promotes osteogenesis and suppresses adipogenic differentiation of multipotent mesenchymal progenitors. J Biol Chem 2003; 27845969-45977. Shao JS, Cheng S-L, Kachigian N, Loewy AP, and Towle, DA Teriparatide [human parathyroid hormone-(1-34)] inhibits osteogenic vascular calcification in diabetic low density lipoprotein receptor-deficient mice. J Biol Chem 2003; 278:50195-50202. Castro CHM, Shin CS, Stains JP, Cheng S-L, Mbalaviele G, Szejnfeld VL, and Civitelli R Targeted expression of a dominant-negative N-Cadherin in vivo delays peak bone mass and increases adipogenesis. J Cell Sci 2004; 117:2853-2864. Sierra OL, Cheng S-L, Loewy, AP, Kachigian N, and Towler DA MINT, the Msx2 interacting nuclear matrix target, enhances Runx2-dependent activation of the osteocalcin fibroblast growth factor response element. J Biol Chem 2004; 279:32913-32923. Mbalaviele G, Sheikh S, Cheng S-L, Stains JP, Chen D and Civitelli R b-Catenin and BMP-2 synergize to promote osteoblast differentiation and new bone formation. J Cell Biochem 2005; 94:403-418. Lai C-F and Cheng S-L avb integrins play an essential role in BMP-2 induction of osteoblast differentiation. J Bone Miner Res 2005; 20:330-340. Shao JS, Cheng S-L (co-first author), Pingsterhaus JM, Kachigian N, Loewy AP and Towler, DA Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals. J Clin Invest 2005; 115:1210-1220.
Division of Bone & Mineral Diseases
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