January 2012 YAO, Zemin EDUCATION: Postdoctoral Research Fellow, Gladstone Foundation Laboratories, University of California, San Francisco, 1991 Postdoctoral Research Fellow, Lipid & Lipoprotein Research Group, University of Alberta, 1988 Ph.D. Biochemistry, University of British Columbia, Canada, 1988 M.Sc. Biochemistry, University of British Columbia, Canada, 1985 B.Sc. Biology, East China Normal University, Shanghai, China, 1982 EMPLOYMENT HISTORY 20022001-02 1995-01 1994-95 1991-94 1991 Professor and Chair, Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Professor, Department of Biochemistry, Microbiology & Immunology, University of Ottawa Associate Professor, Department of Biochemistry, University of Ottawa Assistant Professor, Department of Biochemistry, University of Ottawa Assistant Professor, Department of Biochemistry, University of Alberta Staff Research Investigator, Gladstone Institute of Cardiovascular Disease, University of California, San Francisco EXTERNAL RESEARCH FUNDING Year Source Amount per year 2011 HSF $89,754 (PI) 2011 HSF $73,001 (PI) 2011 CIHR $25,000 (co-PI) 2011 CIHR $30,683 (co-PI) Subject ApoC3 Hypobetalipoproteinemia PCSK9 LRP1 Purpose operating operating operating operating INTERNAL RESEARCH FUNDING Year Source Amount per year 2011 Faculty $50,000 Subject Various Purpose Research PERSONAL STATEMENT I am a Professor in the Department of Biochemistry, Microbiology, and Immunology and the Department of Pathology and Laboratory Medicine at the University of Ottawa. I obtained my MSc and PhD in Biochemistry at the University of British Columbia under the supervision of Dennis Vance, and postdoctoral research training at the Gladstone Institute, UCSF, under the supervision of Thomas Innerarity and Brain McCarthy. In 1991, I was appointed as an Assistant Professor of Biochemistry and established my lab at the Lipid and Lipoprotein Research Group of the University of Alberta with the support from the Alberta Heritage Foundation for Medical Research, the Heart and Stroke Foundation of Canada, the Heart and Stroke Foundation of Alberta, and the Medical Research Council of Canada (now the Canadian Institutes of Health Research or CIHR). In 1994, I joined the University of Ottawa Heart Institute to direct the Molecular and Cell Biology Laboratory of the CIHR Lipoprotein and Atherosclerosis Group. Since 2002, I have been appointed as Chairman of the Department of Biochemistry, Microbiology and Immunology of the University of Ottawa. I was the founding member of the Ottawa Institute of Systems Biology (2004-), the Ottawa Institute of Computational Biology and Bioinformatics (2009-), and the Ottawa Metabolism Research Initiative (2009-). I have a broad research 1 interest in the metabolism of lipids and lipoproteins, and in the relationships between various diseases and the abnormalities in the metabolism of lipoproteins and lipoprotein receptors. I have investigated the lipid and protein factors that regulate the biosynthesis of LDL and HDL, and my research has yielded insights into the molecular mechanisms responsible for various diseases, including familial defective apoB, familial hypobetalipoproteinemia, familial abetalipoproteinemia, and familial combined hyperlipidemia. I am currently investigating several enzymes and proteins that are produced in the liver, and am also investigating the role of lipoprotein receptor in the development of cancer. Our research utilizes modern molecular and cellular biology techniques including genetically modified mice, proteomics and lipodomics approaches, and modern imaging techniques. Our research program is funded through operating grants from the CIHR, grant-in-aids from the Heart and Stroke Foundation of Canada, national training grants funded by CIHR and National Science and Engineering Research Council of Canada. I publish experimental results in scientific journals and regularly present my discoveries at national and international conferences. I am also an active teacher through mentoring postgraduate students in the laboratory and teaching undergraduate, postgraduate, and medical school students. HONORS I was the recipient of scholarships during undergraduate, graduate, and postdoctoral trainings from various agencies, including Chinese Ministry of Education, Alberta Heritage Foundation for Medical Research, and AHA (California). During my academic appoints at various universities and institutes (from 1991 to 2008), I received salary awards from Alberta Heritage Foundation for Medical Research, Heart and Stroke Foundation of Alberta, Heart and Stroke Foundation of Ontario, Medical Research Council of Canada, Canada Institute of Health Research. I have received numerous recognitions and awards from international and national organizations. I was the recipient of the McDonald Scholarship from Award, Heart and Stroke Foundation of Canada, Finalist of the Irvine H. Page Arteriosclerosis Research Award for Young Investigators, American Heart Association, Simon Pierre Noel Lectureship Award and the Senior Investigator Award of the Canadian Lipoprotein Conference, and Ottawa Life Science Council Achievement Award in Basic Research. Currently I am Guest Professor of Shanghai JiaoTong University, and Southwest Jiao Tong University, China. PROFESSIONAL MEMBERSHIPS Member of AAAS (1990-), ASBMCB (1988-); ASCB (1994-2008), AHA (1988-2008), and CSBMCB (1988-2008). Editorial board member for Journal of Biomedical Research (2010-), Journal of Lipids (2010-), Nutrition and Metabolism (2009-), Arteriosclerosis, Thrombosis and Vascular Biology (2011-). GRANT REVIEW PANELS Member of grant review committees of Canadian Institutes of Health Research (1994-) and Heart and Stroke Foundation of Canada (1992-). EDITORIAL MEMBERSHIPS Series Editor of ATVB (2011-); Editor of Journal of Lipids (2010-), Nutrition and Metabolism (2009-), and Journal of Biomedical Research (2011-). PUBLICATIONS (1997-2011): 1. Bamji-Mirza, M., and Yao, Z. Phospholipases. American Oil Chemistry Society Lipid Library (online publication) 2. Zhou, H., Wang, F., Wang, W., Ning, N., Hou, W., Wright, T. G., Sundaram, M., Zhong, S., Yao, Z., and Figeys, D. Improved recovery and identification of membrane proteins from rat hepatic cells using a centrifugal proteomic reactor. Molecular and Cellular Proteomics 10:1-11, 2011 2 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Qin, W., Sundaram, M., Wang, Y., Zhou, H., Chang, C.-C., Manhas, S., Jiang, Z. G., Wang, C., Figeys, D., Jia, W., and Yao, Z. Missense mutation in APOC3 within the C-terminal lipid-binding domain of human apoC-III results in impaired assembly and secretion of triacylglycerol-rich very low density lipoproteins: evidence that apoC-III plays a major role in the formation of lipid precursors within the microsomal lumen. Journal of Biological Chemistry 286:27769-27780, 2011 Bamji-Mirza, M., Sundaram, M., Zhong, S., Yao, E. F., Parks, R., and Yao, Z. Secretion of triacylglycerol-poor VLDL particles from McA-RH7777 cells expressing human hepatic lipase. Journal of Lipid Research, 52:540-548, 2011 Bou Khalil, M., Blais, A., Figeys, D., and Yao, Z. Lipin – The bridge between hepatic glycerolipid biosynthesis and lipoprotein metabolism. Biochimica Biophysica Acta, 1801:1249-1259, 2010 Bou Khalil, M., Hou, W., Zhou, H., Elisma, F., Swayne, L. A., Blanchard, A. P., Yao, Z., Bennett, S. A. L., and Figeys, D. Lipidomics era: accomplishments and challenges. Mass Spectrometry Reviews, 29(6):877-929, 2010 Beaujouin, M., Prébois, C., Derocq, D., Laurent-Matha, V., Masson, O., Pattingre, S., Coopman, P., Bettache, N., Grossfield, J., Hollingsworth, R. E., Zhang, H., Yao, Z., Hyman, B. T., van der Geer, P., Smith, G. K., and Liaudet-Coopman, E. Pro-cathepsin D interacts with the extracellular domain of the β chain of LRP1 and promotes LRP1-dependent fibroblast outgrowth. Journal of Cell Science 123:3336-3346, 2010 Sundaram, M., Zhong, S., Bou Khalil, M., Zhou, H., Jiang, Z. G., Zhao, Y., Iqbal, J., Hussain, M. M., Figeys, D., Wang, Y., and Yao, Z. Functional analysis of the missense APOC3 mutation Ala23Thr associated with human hypotriglyceridemia. Journal of Lipid Research, 51:1524-1534, 2010 Sundaram, M., and Yao, Z. Recent progress in understanding protein and lipid factors affecting hepatic VLDL assembly and secretion. Nutrition and Metabolism, 7:35, 2010 Zhong, S., Magnolo, A. L., Sundaram, M., Zhou, H., Yao, E. F., Leo, E. D., Loria, P., Wang, S., Bamji-Mirza, M., Wang, L., McKnight, J., Figeys, D., Wang, Y., Tarugi, P., and Yao, Z. Nonsynonymous mutations within APOB in human hypobetalipoproteinemia: Evidence for feedback inhibition of lipogenesis and post-endoplasmic reticulum degradation of apolipoprotein B. Journal of Biological Chemistry, 285:6453-6464, 2010 Sundaram, M., Zhong, S., Bou Khalil, M., Links, P. H., Zhao, Y., Iqbal, J., Hussain, M., Parks, R., Wang, Y., and Yao, Z. Expression of apolipoprotein C-III in McA-RH7777 cells enhances VLDL assembly and secretion under lipid-rich conditions. Journal of Lipid Research, 51:150-161, 2010 Robichaud, J. C., van der Veen, J., Yao, Z., Trigatti, B., and Vance, D. E. Hepatic uptake and metabolism of phosphatidylcholine associated with high-density lipoproteins. Biochimica Biophysica Acta, 1790:538-551, 2009 Ye, J., Li, J. Z., Liu, Y., Li, X., Yang, T., Ma, X., Li, Q., Yao, Z., Li, P. Cideb, an ER and lipid droplet-associated protein, mediates VLDL lipidation by interacting with apolipoprotein B. Cell Metabolism 9:177-190, 2009 Bou Khalil, M., Sundaram, M., Zhang, H., Links, P., Raven, J. F., Manmontri, B., Sariahmetoglu, M., Tran, K., Reue, K., Brindley, D., and Yao, Z. The level and compartmentalization of phosphatidate phosphohydrase-1 (lipin-1) control the assembly and secretion of hepatic VLDL. Journal of Lipid Research 50:47-58, 2009 Pan, M., Maitin, V., Lin, S. X., St. Germain, C., Yao, Z. Maxfield, F. R., Williams, K. J., and Fisher, E. A. Pre-secretory oxidation, aggregation, and autophagosomal destruction of apolipoprotein-B: a novel pathway for surprisingly late-stage quality control. Proceedings of National Academy of Science, U.S.A. 105:5862-5867, 2008 Manmontri, B., Sariahmetoglu, M., Donkor, J., Bou Khalil, M., Sundaram, M., Yao, Z. Reue, K., Lehner, R., and N Brindley, D. N. Glucocorticoids and cAMP selectively increase hepatic lipin-1 expression and insulin acts antagonistically. Journal of Lipid Research 49:1056-1067, 2008 3 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. Zhang, H., Lee, J. M., Wang, Y., Dong, L., Ko, K. W. S., Pelletier, L., and Yao, Z. Mutational analysis of the FxNPxY motif within the LDL receptor-related protein1 (LRP1) reveals functional importance of the tyrosine residues in cell growth regulation and signal transduction. Biochemical Journal 409:53-64, 2008 Burnett, J. R., Zhong, S., Jiang, Z. G., Hooper, A. J., Fisher, E. A., McLeod, R. S., Zhao, Y., Barrett, H. R., Hegele, R. A., van Bockxmeer, F. M., Zhang, H., Vance, D. E., McKnight, C. J., and Yao, Z. Missense mutation in APOB within the domain of human apoB-100 result in impaired secretion of apoB and apoB-containing lipoproteins in familial hypobetalipoproteinemia. Journal of Biological Chemistry 282:24270-24283, 2007 Lo, J. C., Wang, Y., Tumanov, A.V., Bamji, M., Yao, Z., Reardon, C. A., Getz, G. S., and Fu, Y. X., LTβR signaling by T cell-derived ligands controls hepatic gene expression for lipid homeostasis. Science, 316:285-288, 2007 Tran, K., Sun, F., Cui, Z., Thorne-Tjomsland, G., St. Germain, C., Lapierre, L. R., McLeod, R. S., Jamieson, J. C., and Yao, Z. Attenuated very low density lipoprotein secretion by eicosapentaenoic acid treatment is associated with impaired utilization of triacylglycerol synthesized via phospholipids remodeling. Biochimica Biophysica Acta, 1761:463-73, 2006. Sun, F., Avramoglu, R. K., Vassiliou, G., Brown, R. J., Ko, K. W. S., McPherson, R., and Yao, Z. Do clustered -propeller domains within the N-terminus of LRP1 play a functional role? Biochimica Biophysica Acta 1721:139-151, 2005. Brown, R. J., Gauthier, A., Parks, R. J., McPherson, R., Sparks, D. L., Schultz, J. R., and Yao, Z. Severe Hypoalphalipoproteinemia in Mice Expressing Human Hepatic Lipase Deficient in Binding to Heparan Sulfate Proteoglycan. Journal of Biological Chemistry 279:42403-42409, 2004. Zhang, H., Links, P. H., Ngess, J. K., Tran, K., Cui, Z., Ko, K. W. S., and Yao, Z. Localization of LDL receptor-related protein (LRP1) to caveolae in 3T3-L1 adipocytes in response to insulin treatment. Journal of Biological Chemistry 279:2221-2230, 2004 Lapierre, L., Currie, D. L., Yao, Z., Wang, J., and McLeod, R. S. Amino acid sequences within the 1 domain of human apolipoprotein B can mediate rapid intracellular degradation. Journal of Lipid Research 45:366-377, 2004. Elzinga, B. M., Baller, J. F. W., Mensenkamp, A. R., Yao, Z., Agellon, L. S., Kuipers, F., Verkade, H. J. Inhibition of apolipoprotein B secretion by taurocholate is independent of lipoprotein assembly in rat hepatoma McArdle-RH7777 cells. Biochimica Biophysica Acta 1635:93-103, 2003. Brown, R. J., Schultz, J. R., Ko, K. W. S., Hill, J. S., Ramsamy, T., White, A. L., Sparks, D. L., and Yao, Z. The amino acid sequences of the carboxyl termini of human and mouse hepatic lipase influence cell surface association. Journal of Lipid Research. 44:1306-1314, 2003. Vukmirica, J., Tran, K., Liang, X., Shan, J., Yuan, J., Miskie, B. A., Hegele, R. A., Resh, M. D., and Yao, Z. The N-linked oligosaccharides at the amino terminus of human apoB are important for the assembly and secretion of VLDL. The Journal of Biological Chemistry. 278:14153-14161, 2003. Burnett, J. R., Shan, J., Miskie, B. A., Hooper, A. J., Yuan, J., Tran, K., Hegele, R. A., and Yao, Z. A novel non-truncating apolipoprotein B gene mutation, R463W, causes familial hypobetalipoproteinemia. Journal of Biological Chemistry. 278:13442-13452, 2003. Ramsamy, T. A., Boucher, J., Brown, R. J., Yao, Z., and Sparks, D. L. HDL regulates the displacement of hepatic lipase from cell surface proteoglycans and the hydrolysis of VLDL triacylglycerol. Journal of Lipid Research. 44:733-741, 2003. Vukmirica, J., Nishimaki-Mogami, T., Tran, K., Shan, J., McLeod, R. S., Yuan, J., and Yao, Z. The N-linked Oligosaccharides at the Amino Terminus of Human Apolipoprotein B Are Important for the Assembly and Secretion of Very Low Density Lipoproteins. Journal of Lipid Research. 43:1496-1507, 2002. 4 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. Tran, K., Thorne-Tjomsland, G., DeLong, C. J., Cui, Z., Shan, J., Burton, L., Jamieson, J. C., and Yao, Z. Intracellular assembly of very low density lipoproteins containing apolipoprotein B100 in rat hepatoma McA-RH7777 Cells. The Journal of Biological Chemistry. 277:31187-31200, 2002. Nishimaki-Mogami, T., Yao, Z., and Fujimori, K. Inhibition of phosphatidylcholine synthesis via phosphatidylethanolamine methylation impairs incorporation of bulk lipids into very low density lipoproteins in cultured rat hepatocytes. Journal of Lipid Research. 43:1035-1045, 2002 Becker, L., McLeod, R. S., Marcovina, S. M., Yao, Z., and Koschinsky, M. L. Identification of a critical residue in apoB100 which is required for Lp(a) assembly. The Journal of Biological Chemistry. 276:36155-36162, 2001 Ko, K. W. S., Avramoglu, R. K., McLeod, R. S., Vukmirica, J., and Yao, Z. The insulin-stimualted cell surface presentation of low density lipoprotein receptor-related protein in 3T3-L1 adipocytes is sensitive to phosphatidylinositide 3-kinase inhibition. Biochemistry. 40:752-759, 2001 Tran, K., Wang, Y., DeLong, C., Cui, Z., and Yao, Z. The assembly of very low density lipoproteins in rat hepatoma McA-RH7777 cells is inhibited by phospholipase A2 antagonists. The Journal of Biological Chemistry. 275:25023-25030, 2000 Wang, Y., Tran, K., and Yao, Z. The activity of microsomal triglyceride transfer protein is essential for accumulation of triglyceride within microsomes in McA-RH7777 cells: a unified model for the assembly of very low density lipoproteins. The Journal of Biological Chemistry. 274:27793-27800, 1999 Nicodeme, E., Benoist, F., McLeod, R. S., Yao, Z., Scott, J., Shoulders, C., and Grand-Perret, T. Identification of domains in Apolipoprotein B100 that confers a high requirement for the Microsomal Triglyceride Transfer Protein. The Journal of Biological Chemistry. 274:1986-1993, 1999 Avramoglu, R. K., Nimpf, J., Ko, K., Wang, Y., FitzGerald, D., and Yao, Z. Functional expression of the chicken LDL receptor-related protein in a mutant CHO cell line restores toxicity of Pseudomonas exotoxin A and degradation of 2-macroglobulin. The Journal of Biological Chemistry. 273:6057-6065, 1998 Tran, K., Borén, J., Macri, J., Wang, Y., McLeod, R. S., Avramoglu, R. K., Adeli, K., and Yao, Z. Functional analysis of disulfide linkages clustered within the amino terminus of human apolipoprotein B. The Journal of Biological Chemistry. 273:7244-7251, 1998 Ko, K. W. S., McLeod, R. S., Avramoglu, R. K., Nimpf, J., FitzGerald, D., Vukmirica, J., and Yao, Z. Mutation at the processing of chicken LDL receptor-related protein impairs efficient endoplasmic reticulum exit but proteolytic cleavage is not essential for its endocytic functions. The Journal of Biological Chemistry. 273:27779-27785, 1998 Gabel, B. R., McLeod, R. S., Yao, Z., and Koschinsky, M. L. Sequences within the amino terminus of apolipoprotein B-100 mediate its non-covalent association with apolipoprotein(a). Arteriosclerosis Thrombosis and Vascular Biology. 18:1738-1744, 1998 Cavallo, D., McLeod, R. S., Rudy, D., Aiton, A., Yao, Z., and Adeli, K. Intracellular Translocation and stability of apolipoprotein B are inversely proportional to the length of the nascent polypeptide. The Journal of Biological Chemistry. 273:33397-33405, 1998 Vermeulen, P. S., Lingrell, S., Yao, Z., and Vance, D. E. Phosphatidylcholine biosynthesis is required for secretion of truncated apolipoprotein Bs from McArdle RH7777 cells only when neutral lipid core is formed. The Journal of Lipid Research. 38:447-458, 1997 Wang, Y., McLeod, R. S., and Yao, Z. Normal activity of microsomal triglyceride transfer protein is required for oleate-induced secretion of very low density lipoproteins in McA-RH7777 cells. The Journal of Biological Chemistry. 272:12272-12278, 1997 Yao, Z., Tran, K., and McLeod, R. S. Intracellular degradation of newly synthesized apolipoprotein B. The Journal of Lipid Research. 38:1937-1953, 1997 5