Principal Investigator
Edison Biotechnology Institute

Associate Professor
Department of Biomedical Sciences
College of Osteopathic Medicine

Faculty Affiliate
Molecular and Cellular Biology Program

Adjunct Associate Professor
Department of Chemistry and Biochemistry
College of Arts and Sciences

Adjunct Associate Professor
Department of Biological Sciences
College of Arts and Sciences

Education

1982
B.S., Chemistry
Tsinghua University, Beijing, China

1988
Ph.D., Biochemistry (Molecular and Cellular Biology)
Ohio University, Athens, OH

Research associates

Scientific Staff
Jae-Kyung Kim, Post-doctoral Fellow

Graduate Students
Yanyan (Joan) Cao
Fengming Liu

Professional activities and memberships

The American Association for the Advancement of Science

The Endocrine Society

Research interests

My lab's major interests in biological and biomedical research include:

Genes and protein factors involved in type 2 diabetes (T2D) and obesity (adipogenesis) for insulin resistance. Insulin resistance is induced by reduced efficiency in insulin signaling that leads to T2D (Figure 1). The mechanism by which insulin resistance is produced is not fully known. Increasing insulin signaling can reduce insulin resistance and improve glucose transport in diabetes patients. We want to study the roles of different genes and protein factors in insulin resistance in fat cells (adipocytes).

Figure 1. Insulin-mediated glucose transport signaling pathway in fat and muscle cells. Insulin activates the insulin receptor (IR) located on the membrane of fat and muscle cells to binding to the alpha-subunit of IR. The binding of insulin to IR triggers phosphorylation of the betasubunit of the receptor and then other protein factors involved in the signaling pathway that eventually leads to translocation of GLUT 4 to the membrane and transportation of glucose into the cells.

A group of novel and potent anti-diabetic and anti-adipogenic compounds has recently been discovered from natural sources in my lab. These compounds have the potential to become new types of therapeutic candidates for treating T2D and its associated obesity, one of the major public health problems in the U.S. The mechanisms by which these compounds work in glucose transport and in adipogenesis inhibition are being intensively investigated in both fat cell lines and in diabetic and obese mouse models. PGG is one of the representative compounds.

Figure 2. GLUT 4 translocation induced by alpha-PGG. When un-induced, GLUT 4 is located intracellularly (left). When it is induced by either insulin or alpha-PGG, GLUT 4 is translocated to the plasma membrane of the cells, forming ring-like structures (middle and right).

Figure 3. Potential receptor targets and signaling pathways for PGG’s adipocyte differentiation inhibitory activity. PGG has an insulin-like glucose transport activity. But it also exhibits an anti-insulin, anti-adipogenic (anti-fat) activity. The two activities appear to be an ideal combination for prevention and treatment of type 2 diabetes. The target and signaling pathway for this activity is being investigated.

Genes involved in early development, particularly in vasculogenesis. Animal cell lines and animals are used for anti-diabetes and anti-obesity mechanism studies, whereas zebrafish is used for developmental biology study using reverse genetics approach. These two seemingly unrelated research projects converge on endothelial cells, which are negatively affected by hyperglycemia in T2D and abnormally developed in and around cancer nodules as a part of the blood supply system. The gene bone morphogenesis protein 4 (bmp4) — which is traditionally thought to be a ventralization signal in early development but its other functions are unclear — has been studied using either a ribozyme-mediated knockdown system or gene over-expression system. These studies have led to the discovery of new functions of bmp4 and improve our understanding of its roles in cardiovascular diseases and in cancer. Endothelial cells will be used as a new model for future study.

Selected publications

Li, Y., Jaekyung Kim, J., Li, J., Liu, F., Liu, X., Himmeldirk, K., Ren, Y., Wagner, T.E., Chen, X. (2005) Natural antidiabetic compound 1,2,3,4,6-penta-O-galloyl-D-Glucopyranose (PGG) binds to insulin receptor and activates insulin-mediated glucose transport signaling pathway. Biochem Biophy Res Commu 336: 430-437.

Liu, X., Kim, J., Li, Y., Li, J., Liu, F., Chen, X. (2005) Tannic acid stimulates glucose transport and inhibits adipocyte differentiation in 3T3-L1 cells. J Nutr 135, 165-171.

He, C., and Chen, X. (2005) Transcription regulation of the vegf gene by the BMP/Smad pathway in the angioblast of zebrafish embryos. Biochem Biophy Res Commu 329:324-330.

Ren, Y., Zhou, Y., Chen, X., Ye, Y. (2005) Discovery, structural and bioactivity study of food-originated anticancer agents. Letters in Drug Design and Discovery. 2:444-450.

Li, Y., Hatfield, S., Li, J., McMills, M., Yufen Zhao, Y., & Chen X. (2002) Seryl-histidine as an alternative DNA nicking agent in nick translation yields superior DNA probes and hybridizations. Bioorg. Medicinal Chem. 10: 667-673.

Walker, K., Xie, Y., Li, Y., Zhu, Q., Xu,W.,Wagner, T.E. and Chen, X. (2001) Cytoplasmic Expression of Ribozyme in Zebrafish Using a T7 Autogene System. Current Issues of Molecular Biology. 3: 1-6.

Liu, F., Kim, J., Li, Y., Liu, X., Li, J., Chen, X. (2001) An extract of Lagerstroemia speciosa L. has insulin-like glucose uptake-stimulatory and adipocyte differentiation-inhibitory activities in 3T3-L1 cells. J Nutr 131, 2242-2247.

Li, Y., Zhao, Y., Hatfield, S.,Wan, R., Zhu, Q., Li, X., McMills, M., Ma, Y., Li, J., Brown, K., He, C., Liu, F. and Chen, X. (2000). Dipeptide seryl-histidine and related oligopeptides cleave DNA, protein, and a carboxylester. Bioorg. Medicinal Chem. 8: 2675-2680.

Wang, Y., Chen, X. and Colvin, R. (2000). Expression of the Na+/Ca2+ exchanger ameliorates ionomycin-induced cell death. Biochem. Biophy. Res. Comm. 276: 93-97.

Xie, Y., Li, Y.,Walker, K., Zhu, Q.,Wagner, T., and Chen, X. (1999) Cytoplasmic expression of ribozyme using a T7 autogene system. Intracellular Ribozyme Application: Principles and Protocols. Horizon Scientific Press. U.K. pp. 69-78.

Sturtz, F., Li, Y., Shulok, J., and Chen, X. (1999) A nonviral cytoplasmic T7 autogene system and its applications in DNA vaccination in DNA vaccines: Methods and Protocols in the series of Methods in Molecular Medicine. Humana Press. pp. 323-333.

Chen, X., Li, Y., Xiong, K., Xie, Y., Aizicovici, S.,Wagner, T., and Platika, D. (1998). Cancer gene therapy by direct injection of a nonviral T7 cytoplasmic expression vector encoding a thymidine kinase gene. Human Gene Therapy 9:729-736.

Kopchick, J., Chen, X., Li, Y., Steger, R., Yun, J.,Wagner, T., and Bartke, A. (1998) Differential in vivo activities of bovine growth hormone analogs. Transgenic Research, 7:61-71.

Xie, Y., Chen, X., and Wagner, T.E. (1997) A Novel ribozyme mediated, gene "knockdown" strategy for the identification of gene function in zebrafish. Proc Natl. Acad. Sci. USA. 94: 13777 - 13781.

Sturtz, F. G.,Waddell, K., Shulok, J., Chen, X., Caruso, M., Sanson, M., Snodgrass, H. R., and Platika, D. (1997) Variable efficiency of the thymidine kinase/ganciclovir system in human glioblastoma cell lines: Implications for gene therapy. Human Gene Therapy 8:1945-1953.

Sturtz F.,Waddell K., Shulok J., Chen X., Snodgrass HR., Platika D. (1997) Parameters influencing the efficiency of the thymidine kinase/ganciclovir (TK/GCV) system in human glioblastoma cell lines. Stereotactic and Functional Neurosurgery 68:252-257.

Chen, X., Li, Y., Xiong, K., Xie, Y., Aizicovici, S., Snodgrass, R.,Wagner, T.E., and Platika, D. (1995) A novel nonviral cytoplasmic gene expression system and its implications in cancer gene therapy. Cancer Gene Therapy, 2: 281-289.

Prieto, P.A., Mukerji, P., Kelder, B., Erney, R., Gonzalez, D., Yun, J., Smith, D., Moreman, K.W., Nardelli, C., P ierce, M., Li, Y., Chen, X., Wagner, T.E., Cummings, R.D., and Kopchick, J.J. (1995) Remodeling of mouse milk glycoconjugates by transgenic expression of a human glycosyltransferase. Journal of Biological Chemistry, 270: 29515-29519.