Pharmacology and Toxicology

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Xiao-Mei Qi, MD

Assistant Professor
Phone: 414 955-5643
Fax: 414-955-6545
xiaoqi@mcw.edu

Education:
MD - Bengbu Medical College, Anhui, China - 1982

Qi's Faculty Collaboration Database


Research Interest

Cancer is a leading cause of human death and development of better therapeutics is a major task for cancer research. Nuclear receptors are a group of proteins that act as transcription factors to regulate gene expression in response to ligand treatment. Our major research interest is to explore novel functions of nuclear receptors in regulating therapeutic stress response by dissecting their signaling cross-talk with stress MAPKs.

Our studies have established that vitamin D receptor (VDR) is a stress responsive protein and its expression is induced by stress signaling through c-Jun/AP-1 pathways, which in turn inhibits stress-induced cell death. In human colon cancer cells, K-Ras mutation was shown to inactivate the VDR stress-regulatory pathway leading to an increased cell-death in response to stress p38 MAPK activation. In human breast cancer cells, on the other hand, our studies showed that estrogen receptor (ER) may inhibit stress-induced c-Jun-dependent cell death through a direct protein-protein interaction. These results together suggest that nuclear receptor VDR and ER may have dual biological roles: in response to ligand, they act as a receptor to mediate ligand-induced specific response through transcriptional regulations; in response to stress they function as a cell-death inhibitor through interacting and/or crosstalking with c-Jun-dependent pathways. Regulation of VDR/ER activity may consequently correspond to a novel strategy to increase cancer therapeutic response.             


Recent Publications

Hou, S., Padmanaban, S., Qi, X., Lepp, A., Mirza, S. P., and Chen, G. (2012) p38g MAPK signals through phosphorylating its phosphatase PTPH1 in regulating Ras oncogenesis and stress response. J Biol Chem, 287: 27895-27950 PMID:22730326

Yusuke Kobayashi*, Xiaomei Qi*, and Chen, G. (2012) MK2 regulates Ras oncogenesis through stimulating ROS production. Genes & Cancer, 3: 521-530 (*contributed equally) PMID:23264852 PMCID:3527985

Qi, X., Zhi, H., Lepp, A., Wang, P., Huang, J., Zainab Basir, Z., Chitambar, C. R., Chen, G. (2012) p38y MAPK confers breast cancer hormone sensitivity by switching estrogen receptor (ER) signaling from the classical to non-classical pathway via stimulating ER phosphorylation and c-Jun transcription. J Biol Chem, 287: 14681-14691

Qi, X., Hou, S., Lepp, A., Li, R., Basir, Z., Lou, Z., Chen, G. (2011) Phosphorylation and stabilization of topoisomerase IIMAPK sensitize breast cancer cells to its poisons. J. Biol. Chem. 286:35883-35890

Loesch, M., Ahi, H., Hou, S., Qi, X., Li, R., Basir, Z., Iftner, T., Cuenda, A., and Chen, G. p38Y MAPK cooperates with C-Jun in Trans-activating Matrix Metalloproteinase 9. (2010), J. Biol. Chem. 2010, 185: 15149-15158

Hou, S., Zhi, H., Pohl, N., Loesch, M., Qi, X., Li, R., Basir, Z., and Chen, G. PTPH1 dephosphorylates and cooperate with p38Y MAPK to increase Ras oncogenesis through PDZ-mediated interaction. (2010), Cancer Res. 70: 2901-2910.

Qi, X.M*., Pohl, N.M*., Loesch, M., Hou, S., Li, R., Qin, J. Z., Cuenda, A., and Chen, G. (2007) p38alpha antagonizes p38gamma activity through c-Jun-dependent ubiquitin-proteasome pathways in regulating Ras transformation and stress response. J Biol Chem 282: 31398-31408 (*contributed equally to the work).

Qi, X., Li, Q-P., Pramanik, R., Pohl, N. M., Loesch, M. and Chen, G. (2007) Stress-induced c-Jun-dependent vitamin D receptor (VDR) activation dissects the non-classical VDR pathway from the classical VDR activity. J. Biol. Chem., 282: 1544-1551. (QX and LQ contributed equally to this work).

Qi, X., Tang, J., Loesch, M., Pohl, N., Alkan, S. and Chen, G. (2006) p38g mitogen-activated protein kinase integrates signaling crosstalk between Ras and estrogen receptor to increase breast cancer invasion. Cancer Res., 66: 7540-7547.  

Tang, J., Qi, X. M, Mercola, D., Han, J., and Chen, G.:  (2005) Essential role of p38g in K-Ras transformation independent of phosphorylation. J. Biol. Chem. 280:23910-23917 (Recommended by Faculty 1000 of Biology, May 13, 2005).

Qi, X. M., Tang, J., Pramanik, R., Schultz, R. M., Shirasawa, S., Sasazuki, T., Han, J., and Chen, G.:  (2004) p38 MAPK activation selectively induces cell death in K-ras mutated human colon cancer cells through regulation of vitamin D receptor. J. Biol. Chem. 279: 22138-22144.

Qi, X. M., Borowicz, S., Pramanik, R., Schultz, R. M., Han, J., and Chen, G.:  (2004) Estrogen receptor inhibits c-Jun-dependent stress-induced cell death by binding and modifying c-Jun activity in human breast cancer cells. J. Biol. Chem. 279: 6769-6777.

Pramanik, R., Qi, X. M, Borowicz, S., Choubey, D., Schultz, R. M., Han, J., and Chen, G.:  (2003) p38 isoforms have opposing effects on AP-1-dependent transcription through regulation of c-Jun: The determinant role of the isoforms in the p38 MAPK signal specificity.  J. Biol. Chem. 278: 4831-4839.

Qi, X. M., Pramanik, R., Wang, J., Schultz, R. M., Maitra, R. K., Han, J., DeLuca, H. F., and Chen, G.:  (2002) The p38 and JNK pathways cooperate to trans-activate vitamin D receptor via c-Jun/AP-1 and sensitize human breast cancer cells to vitamin D3-induced growth inhibition. J. Biol. Chem.  277: 25884-25892.

Payne, S. L., Celle, K. L., Pei, X. F., Qi, X. M., Shao, H., Steagal, W. K., Perry, S., and Fuller, F.:  (1999) Long terminal repeat sequences of equine infections anaemia virus are a major determinant of cell tropism.  J. Gen. Virol.  80: 755-759.

Payne, S., Qi, X. M., Shao, H., Dwyer, A., and Fuller, F. J.:  (1998) Disease induction by virus derived from molecular clones of equine infection anemia virus.  J. Virol., 72: 483-487.

He, H., Qi, X. M., Grossmann, J., and Distelhorst, C.: (1998) c-Fos degradation by the proteasome, an early Bcl-2-regulated step in apoptosis.  J. Biol. Chem., 273: 25015-25019.

Qi, X. M., He, H., Zhong, H. and Distelhorst, C.:  (1997) Baculovirus p35 and Z-VAD-fmk inhibit thapsigargin-induced apoptosis of breast cancer cells. Oncogene, 15: 1207-1212.

Qi, X. M., Simonson, M. and Distelhorst, C.:  (1997) Bcl-2 inhibits c-Fos induction by calcium. Oncogene, 15: 2849-2853.

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