Shi Lab

Yuguang (Roger) Shi, Ph.D.

Lab Interest:

Ground breaking projects focus on molecular mechanisms underlying a regulatory role of defective cardiolipin remodeling by ALCAT1 in the mitochondrial dysfunction associated with diabetes obesity using molecular, cellular, transgenic, knockout, and lipidomic approaches. Another project focuses on molecular mechanisms underlying glucose sensing by pancreatic β-cells which plays a pivotal role in regulating glycemic control and the onset of type 2 diabetes. Using gain and loss function, we investigate a major role of PBK1 kinase in regulating glucose sensing network and the onset of type 2 diabetes. We have also identified several novel signal transduction pathways mediated by PBK1. http://www.pennstatehershey.org/web/physiology/home/faculty
 

Publications (Selected):

1. Hao, X., Wang, Y., Ren, F., Zhu, S., Ren, Y., Jia, B., Y-P, Li, Shi, Y. and Chang, Z. (2011). SNX25 regulates TGF-β signaling by enhancing the receptor degradation. Cell Signal. 23(5):935-46.

2. Zhu, Y., Shu, T., Lin, Y., Wang, H., Yang ,J., Shi Y, and Han X.(2011) Inhibition of the receptor for advanced glycation endproducts (RAGE) protects pancreatic β-cells. Biochem. Biophys. Res. Commun. 404(1):159-65.

3. Li, J., Romestaing, C., Han X., Li, Y., Hao, X., Wu Y., Sun, C., Jefferson, L. S., Xiong, J., LaNoue, K.F., Chang, Z., Lynch, C.J., Wang, H., and Shi*, Y. (2010) Cardiolipin Remodeling by ALCAT1 Links Oxidative Stress and Mitochondrial Dysfunction to Obesity. Cell Metab. 12, 154-165.

4. Shi, Y. (2010) Emerging Roles of Cardiolipin Remodeling in Mitochondrial Dysfunction Associated with Diabetes, Obesity, and Cardiovascular Diseases. J. Biomed. Res. 24(1):6-15.

5. Nie, J., Hao, X., Chen, D., Han, X., Chang, Z., and Shi*, Y. (2009) A Novel Function of the Human CLS1 in Phosphatidylglycerol Synthesis and Remodeling. Biochim. Biophys. Acta-Mol. & Cell Biol. Lipids 1801(4):438-445.

6. Cheng, L., Han, X., and Shi*, Y. (2009) A Regulatory Role of LPCAT1 in the Synthesis and Remodeling of Inflammatory Lipids, PAF and LPC, in Diabetic Retinopathy. Am. J. Physiol. Endocrinol. Metab. 297(6):E1276-82.

7. Shi*, Y. and Dong Cheng (2009). Beyond Triglycerol Synthesis: The Dynamic Functional Roles of MGAT and DGAT Enzymes in Energy Metabolism. Am. J. Physiol. Endocrinol. Metab. 297(1):E10-8.

8. Cao, J., Shen, W., Chang Z., and Shi*, Y. (2008) ALCAT1 Is a Polyglycerophospholipid Acyltransferase Potently Regulated by Adenine Nucleotides and Thyroid Status. Am. J. Physiol. Endocrinol. Metab. 296(4):E647-53

9. Li, X., Huang, M., Zheng, H., Wang, Y., Ren, F., Shang, Y., Zhai, Y., Irwin, D.M., Shi, Y., Chen, D., and Chang, Z. (2008). CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation. J. Cell Biol. 181(6):959-72

10. Shi, Y. (2007) Anti-obesity Pharmacotherapy: Current Treatment Options and Future Perspectives. Handbook of Contemporary Neuropharmacology. (David Sibley, et al., eds.) John Wiley & Sons, Inc., Hoboken, NJ. Volume 3: 815-843

11. Cao, J., Cheng, L., and Shi*, Y. (2007) MGAT3 is a putative triacylgycerol synthase with preference of 1,3-diacylglycerols as substrates. J. Lipid Res. 48(3):583-91

12. Van, Q., Liu, J., Lu, B., Feingold, K.R., Shi, Y., Lee, R.M., and Hatch G.M. (2006) Phospholipid scramblase-3 regulates cardiolipin de novo biosynthesis and its resynthesis in growing Hela cells. Biochem. J. 401(1):103-9

13. Chen, D., Zhang X-Y, and Shi*, Y. (2006) Identification and functional characterization of hCLS1, a human cardiolipin synthase localized in mitochondria. Biochem. J. 398 (2): 169-176.

14. Zhang, S., Yang, Y, and Shi*, Y. (2005) Characterization of human SCD2, an oligomeric desaturase with improved stability and enzyme activity by cross-linking in intact cells. Biochem. J. 388 (1): 135-142.

15. Yang, Y., Cao, J., and Shi*, Y. (2004) Identification and characterization of a human gene encoding an ER-associated lysophosphatidylglycerol acyltransferase. J. Biol. Chem. 279(53):55866-74.

16. Shi, Y. (2004) Beyond skin color: emerging roles of melanin-concentrating hormone in energy homeostasis and other physiological functions. Peptides 25 (10): 1605-1611.

17. Shi, Y. and Burn, P. (2004) Lipid metabolic enzymes: emerging molecular drug targets for treatment of obesity. Nat. Rev. Drug Discov. 3 (8): 695-710.

18. Cao, J., Liu, Y., Lockwood, J., Burn, P., and Shi*, Y. (2004) A novel pathway involved in cardiolipin remodeling revealed by functional characterization of a gene encoding ER-associated lysocardiolipin acyltransferase in mouse. J. Biol. Chem. 279(30):31727-34.

19. Gao, X., Hsu, A, Heinz, L., Morin, J., Shi, Y., Shukla, N., Smiley, D., Xu, J. , Zhong, B., and Slieker, L. (2004) Europium-labeled melanin concentrating hormone analogues: novel ligands for measuring binding to both melanin concentrating hormone receptor 1 and 2. Anal. Biochem. 328 (2):187-195.

20. Cao, J., Hawkins, E., Brozinick, J.T., Liu, X., Zhang, H., Burn, P., and Shi*, Y. (2004). A predominant role of MGAT2 in dietary absorption implicated by tissue distribution, subcellular localization, and up-regulation by high fat diet. J. Biol. Chem. 279(18):18878-86.

21. Lockwood, J., Cao, J., Burn, P., and Shi*, Y. (2003). A human intestinal monoacylglycerol acyltransferase: differential features in tissue expression and activity. Am. J. Physiol. Endocrinol. Metab. 285(5):E927-37.

22. Cao, J., Burn, P., and Shi*, Y. (2003) Properties of the mouse intestinal acyl-CoA:monoacylglycerol acyltransferase, MGAT2. J. Biol. Chem. 278(28):25657-63.

23. Shi, Y., Taylor, S.I., Tan, S.L, and Sonenberg, N. (2003). When translation meets metabolism: multiple links to diabetes. Endocr. Rev. 24, 91-101

24. Cao, J., Lockwood, J., Burn, P., and Shi*, Y. (2003) Cloning and functional characterization of a mouse intestinal acyl-CoA:monoacylglycerol acyltransferase, MGAT2. J. Biol. Chem. 278(16):13860-6

25. Tan, S.L, Pause, A., Shi, Y., and Sonenberg, N. (2002). Anti-HCV therapeutics: current status and emerging strategies. Nat. Rev. Drug Discov. 1, 867-881.

26. Chen, Y., Hu, H., Hsu, C.-K., Zhang, Q., Bi, C., Asnicar, M., Hsiung, H.M., Fox, N., Slieker, L.J., Yang, D.D., Heiman, M.L., and Shi*, Y. (2002). Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity. Endocrinology: 143, 2469-2477.

27. Wu, S., Hu, Y., Wang, J-L, Chatterjee, M., Shi, Y., and Kaufman, R.J. (2002) Ultraviolet light inhibits translation through activation of the unfolded protein response kinase PERK in the lumen of the endoplasmic reticulum. J. Biol. Chem. 277, 18077-18083.

28. De la Serna, I., Cujec, T.P., Shi, Y., and Tyler, B.M. (2000). Non-coordinate regulation of 5S rRNA gene and the gene encoding the 5S rRNA-binding ribosomal protein homolog in Neurospora crassa. Mol. & Gen. Genet. 263, 987-994.

29. Shi, Y., Kanaani, J., Menard-Rose, V., Ma, Y.H., Chang, P-Y., Tobin, A., Hanahan, D., Tobin, A., Grodsky, G., and Baekkeskov, S. (2000). Increased expression of glutamic acid decarboxylase and GABA in pancreatic ¿-cells impairs first phase insulin secretion. Am. J. Physiol. Endocrinol. Metab. 279, E684-E694.

30. Hayes, S.E., Conner, L. J., Stramm, L.E, and Shi*, Y. (1999). Assignment of pancreatic eIF-2¿ kinase (EIF2AK3) to human chromosome band 2p12 by radiation hybrid mapping and in situ hybridization. Cytogen. & Cell Genet. 86, 327-328.

31. An, J., Zhao, G., Churgay, L.M., Osborne, J.J., Hale, J.E., Becker, G.W., Gold, G., Stramm, L.E., and Shi*, Y. (1999). Threonine Phosphorylations Induced by RX871024 and Insulin Secretagogues in ¿TC6-F7 Cells. Am. J. Physiol. Endocrinol. Metab. 277, E862-E869.

32. Shi*, Y., An, J., Liang, J, Hayes, S.E., Sandusky, G.E., Stramm, L.E., and Yang, N.N. (1999). Characterization of a mutant pancreatic eIF-2¿ kinase, PEK, and co-localization with somatostatin in islet ¿¿Cells. J. Biol. Chem. 274, 5723-5730.

33. Shi*, Y., Vattem, K.M., Sood, R., An, J., Liang, J.D., Stramm, L.E., and Wek, W.C. (1998). Identification and characterization of pancreatic eIF-2¿ kinase, PEK, involved in translational control. Mol. & Cell. Biol. 18, 7499-7509. (Reviewed in Nature 397:208-209, PEK is renamed to PERK)

*The corresponding author

Program Affiliations:
Physiology, Genetics, Cell & Molecular Biology.

PH: 717/531-0003, Ext. 283789; e-mail: yus11@psu.edu