Current Research Activities A proper balance between synthesis, maturation and degradation of cellular proteins is crucial for cells to function properly. The costly process of protein synthesis is tightly coupled to energy status and nutrient levels by mTOR signaling pathway, whereas the quality of newly synthesized polypeptides is largely maintained by molecular chaperone and ubiquitin-proteasome systems. Our laboratory has a long standing interest in the molecular connection between the cytosolic stress response and nutrient signaling pathways. By disrupting the chaperone network using genetic approach, we are investigating the protein homeostasis at the cellular and organismal levels. In addition, we are interested in the translational regulation of gene expression in growth and diseases. Using advanced technology such as ribosome footprinting coupled with deep sequencing, we are deciphering the coordination between nutrients and chaperones in the regulation of protein synthesis. Because of the central role of protein synthesis in growth and aging, the elucidation of the regulatory mechanism of translation may offer novel opportunities for treating human diseases, such as cancer, diabetes and neurodegenerative disorders.
Biography
Biographical Statement Dr. Shu-Bing Qian received his MSc and PhD degrees in Molecular Biology & Biochemistry with honors in 1997 and 2000, respectively, from Shanghai Jiaotong University Medical School (formerly Shanghai Second Medical University). He then conducted two postdoctoral fellowships at the National Institutes of Health (Bethesda, MD) and University of North Carolina (Chapel Hill, NC) in the field of Biochemistry. Before he joined Cornell University, he was a Research Assistant Professor at UNC (2006-2008). He became an Assistant Professor in the Division of Nutritional Sciences at Cornell University in July 2008. In 2009, Dr. Qian received Young Investigator Award from Ellison Medical Foundation, and NIH Director's New Innovator Award.
Most of the work in Dr. Qian's laboratory is broadly interdisciplinary, with a primary emphasis on the nutrient signaling pathway and protein synthesis. Using biochemical, genetic, and cell biology approach, the Qian laboratory investigates nutritional and genetic determinants of adaptive stress response and the respective implications in human diseases, especially aging and age-related pathologies. Specific research interests include chaperone network and ubiquitin/proteasome system, nutrient sensing pathway mTOR (the mammalian target of rapamycin), and translational regulation of gene expression. Motivated by potential application to health issues, the Qian laboratory is dedicated to understanding the molecular basis of aging and age-related diseases, such as diabetes, cancer, and neurodegenerative disorders.
Education PostDoc, 2004 ~ 2008 University of North Carolina, Chapel Hill, NC PostDoc, 2000 ~ 2004 National Institutes of Health, Bethesda, MD Ph.D., 2000 Shanghai Jiaotong University Medical School, Biochemistry M.Sc., 1997 Shanghai Jiaotong University Medical School, Biochemistry
Keywords chaperone, ubiquitin-proteasome system, nutrients signaling, stress response, protein translation, protein degradation, aging,
Courses, Websites, Pubs
Courses Taught BIOG4990 - Independent Research in Biology II NS4010 - Empirical Research NS3200 - Human Biochemistry
Qian SB, Waldren L, Choudhary N, Klevit RE, Chazin WJ, Patterson C. Engineering a ubiquitin ligase reveals conformational flexibility required for ubiquitin transfer. J Biol Chem2009 ; 284(39):26797-802
McDonough H, Charles PC, Hilliard EG, Qian SB, Min JN, Portbury AL, Cyr DM, Patterson C. Stress-dependent chip/DAXX interaction suppresses the p53 apoptotic program. J Biol Chem2009 ; 284(31): 20649-59
Xia T , Dimitropoulou C , Zeng J , Antonova GN , Snead C , Venema RC , Fulton D , Qian SB , Patterson C , Papapetropoulos A , Catravas JD . Chaperone-dependent E3 ligase CHIP ubiquitinates and mediates proteasomal degradation of soluble guanylyl cyclase. Am J Physiol Heart Circ Physiol2007; 293:H3080-3087
Qian SB, McDonough H, Boellmann F, Cyr DM, Patterson C. CHIP-mediated stress recovery by sequential ubiquitination of substrates and Hsp70. Nature 2006; 440: 551-555
Qian SB, Reits E, Neefjes J, Deslich JM, Bennink JR, and Yewdell JW. Tight linkage between translation and MHC-class I peptide ligand generation implies specialized antigen processing for defective ribosomal products. J Immunol2006; 177: 227-233
Qian SB, Princiotta MF, Bennink JR, Yewdell JW. Characterization of rapidly degraded polypeptides in mammalian cells reveals a novel layer of nascent protein quality control. J Biol Chem2006; 281(1):392-400
Dai Q, Qian SB, Li HH, McDonough H, Borchers C, Huang D, Takayama S, Younger JM, Ren HY, Cyr DM, Patterson C. Regulation of the cytoplasmic quality control protein degradation pathway by BAG2. J Biol Chem2005; 280(46):38673-38681
Shaffer AL, Shapiro-Shelef M, Iwakoshi NN, Qian SB, Zhao H, Yu X, et al. XBP1 acts downstream of Blimp-1 to regulate ER biogenesis, oeganelle expansion, and protein synthesis during plasma cell differentiation. Immunity 2004; 21(1):81-93
Qian SB, Ott DE, Schubert U, Bennink JR, Yewdell JW. Fusion proteins with COOH-terminal ubiquitin are stable and maintain dual functionality in vivo. J Biol Chem2002; 277(41):38818-38826
Qian SB, Li Y, Qian GX, and Chen SS. Efficient tumor regression induced by genetically engineered tumor cells secreting interleukin-2 and membrane-expressing allogeneic MHC class I antigen. J Cancer Res Clin Oncol 2001; 127(1): 27-33
Qian SB, and Chen SS. Blocked transport of soluble Kb molecules containing connecting peptide segment involved in calnexin association. Int Immunol2000; 12(10): 1409-1416
Xie Q, Liao D, Zhou XQ, Qian SB, Cheng SS. Transduction of primary rat hepatocytes with bicistronic retroviral vector. World J Gastroenterol2000; 6(5):725-729
Qian SB, Qian GX, and Chen SS. Enhanced immunogenecity of human hepatocellular carcinoma cells transduced with human gamma-interferon gene via retroviral vector. Acta Univ Med 2nd Shanghai1999; 11(2): 90-94
Qian SB, and Chen SS. Transduction of human hepatocellular carcinoma cell lines transduced with human gamma-interferon gene via retroviral vector. World J Gastroenter1998; 4(3): 210-213
Qian SB, Zhang TF, and Chen SS. Enhanced expression of HLA class I molecules in human hepatocellular carcinoma cell lines transduced with human gamma-interferon gene. Chin Med J (Eng)1998; 111(4): 319-322