|Credentials:||2001 - Ph.D., Iowa State University|
|Mailing Address:||Animal Sciences|
PO Box 646310
Pullman, WA 99164-6310
Developmental origins of adult diseases (fetal programming); Epigenetic regulation of stem cell differentiation; myogenesis and adipogenesis
Our research is focused on the epigenetic regulation of fetal development, focusing on skeletal muscle and adipose tissue. Specifically, we are interested in exploring mechanisms regulating the differentiation of mesenchymal stem cells into myocytes and adipocytes, and the impact of maternal physiological conditions on the development of fetal skeletal muscle and adipose tissue.
For human health, obesity, including maternal obesity, is increasing at an alarming rate. Skeletal muscle is the major tissue responsible for glucose and fatty acid utilization, and excessive adipose tissue is responsible for obesity. Both skeletal muscle and adipose tissue are primarily developed during the fetal stage. Abnormal muscle and adipose development of the fetuses or neonates due to maternal obesity pre-dispose offspring to adult diseases such as obesity and type II diabetes. But the underlying mechanisms remain poorly defined. Currently, we are exploring the impact of maternal nutrition on the expression of key transcription factors initiating early adipogenic and myogenic commitment of progenitor cells.
For animal agriculture, maternal nutrition especially under-nutrition impacts fetal muscle development and the subsequent animal performance and meat quality. Maternal nutrient deficiency permanently reduces offspring muscle mass but increases fatness. Low lean/fat ratio is associated with huge waste in animal production. On the other hand, intramuscular fat (marbling) is critically important for the palatability of meat. Because both adipocytes and muscle cells are developed from a common pool of progenitor cells, effective manipulation of progenitor cell differentiation can profoundly affect animal production efficiency and meat quality.
Our objective is to define mechanisms, especially environmental factors such as nutrition, which regulate the differentiation of mesenchymal progenitor cells into myocytes and adipocytes during fetal development. These studies have applications to both human medicine and animal agriculture.
We use in vitro cell culture, transgenic mice and livestock as experimental models. A wide range of laboratory techniques are used in our studies, including chemical analyses, enzyme activity assays, immunoblotting, ELISA, immunohistochemical staining, 2-dimensional gel electrophoresis and proteomic analyses, real-time PCR, DNA manipulation, RNA interference and epigenetic analyses.
(For complete publication list, visit Research Gate: https://www.researchgate.net/profile/Min_Du4)
Fu, X., j.X. Zhao, X., M.J. Zhu, M. Foretz, B. Viollet, M.V. Dodson, and M. Du. (2013) AMP-activated protein kinase a1 but not a2 catalytic subunit potentiates myogenin expression and myogenesis. Molecular and Cell Biology, 33: 4517-4525.
Fu, X., J.X. Zhao, J.F. Liang, M.J. Zhu, M. Foretz, B. Viollet, and M. Du. (2013). AMP-activated protein kinase mediates myogenin expression and myogenesis via histone deacetylase 5. American Journal of Physiology-Cell Physiology, 305: C887-895.
Yang, Q.Y., J.F. Liang, C.J. Rogers, J.X. Zhao, M.J. Zhu, and M. Du. (2013). Maternal obesity induces epigenetic modifications to facilitate Zfp423 expression and enhance adipogenic differentiation in fetal mice. Diabetes, 62:3727-3735.
Du, M., Y. Huang, A.K. Das, Q. Yang, M.S. Duarte, M.V. Dodson, and M.J. Zhu. (2013). Manipulating mesenchumal progenitor cell differentiation to optimize performance and carcass value of beef cattle. Journal of Animal Science, 91: 1419-1429.
Yan, X., Y. Huang, J.X. Zhao, C.J. Rogers, M.J. Zhu, S.P. Ford, P.W. Nathanielsz, and M. Du. (2013). Maternal obesity down-regulates microRNA (miRNA) let-7g expression, a possible mechanism for enhanced adipogenesis during ovine fetal skeletal muscle development. International Journal of Obesity, 37:568-575.
Huang, Y., J.X. Zhao, X. Yan, M.J. Zhu, N.M. Long, R.J. McCormich, S.P. Ford, P.W. Nathanielsz, and M. Du. (2012) Maternal obesity enhances collagen accumulation and cross-linking in skeletal muscle of ovine offspring. PLOS one, 7, e31691.
Yan, X., Y. Huang, J.X. Zhao, N.M. Long, A.B. Uthlaut, M.J. Zhu, S.P. Ford, P.W. Nathanielsz, and M. Du. (2011). Maternal obesity impaired insulin signaling and induced lipid accumulation and fibrosis in skeletal muscle of offspring. Biology of Reproduction, 85:172-178.
Zhao, J.X., W.F. Yue, M.J. Zhu, and M. Du. (2011). AMP-activated protein kinase regulates b-catenin transcription via histone deacetylase 5. Journal of Biological Chemistry, 286:16426-16434.
Huang, Y., X. Yan, J.X. Zhao, M.J. Zhu, R.J. McCormick, S.P. Ford, P.W. Nathanielsz, J. Ren, and M. Du. (2010). Maternal obesity induces fibrosis in fetal myocardium of sheep. American Journal of Physiology-Endocrinology and Metabolism, 298:E1254-1260.
Yan, X., M.J. Zhu, W. Xu, J.F. Tong, S.P. Ford, P.W. Nathanielsz, and M. Du. (2010). Up-regulation of TLR4/NF-кB signaling is associated with enhanced adipogenesis and insulin resistance in fetal skeletal muscle of obese sheep at late gestation. Endocrinology, 151:380-387.
Tong, J.F., X. Yan, M.J. Zhu, S.P.Ford, P.W. Nathanielsz, and M. Du. (2009). Maternal obesity down-regulates myogenesis and β-catenin signaling in fetal skeletal muscle. American Journal of Physiology-Endocrinology and Metabolism, 296, E917-924.