Annual Report 2011 - Center for Advanced Biotechnology and ...

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(CHINJ, CINJ and CABM) and Lauri Goodell (RWJUH) characterized the effects of mesenchymal stromal cell (MSC) on the survival and drug resistance of primary mantle cell lymphoma (MCL) cells, an aggressive subtype of non- Hodgkin’s lymphoma. Studies revealed an important role for the canonical and non-canonical NF-kB pathways and expression of cytokine BAFF by MSC in the long term survival of MSC. A manuscript was submitted (Medina et al. Submitted). Finally, we pursued our collaborative work with Dr. Eileen White (CINJ) on the role of autophagy in tumorigenesis and the role of NF-kB in this context. These studies uncovered that activated Ras, commonly found in human tumors, requires autophagy to maintain oxidative metabolism and tumorigenesis. This suggests that therapeutic strategies to inhibit autophagy could perhaps be useful for the treatment of cancers in which Ras is activated. This work was published (Guo et al. 2011). Ongoing studies focus on understanding how p62 modulates autophagy and tumorigenesis and the role of NF-kB in this context, expressed and purified active fragment was crystallized and the structure determined by X-ray crystallography. Seven related conformational states were obtained in the crystal. Position differences of the oligonucleotide/oligosaccharide (OB) binding fold lid domain over the conserved GTP binding site in the seven structures provided snapshots of the opening and closing of the active site cleft via a swivel motion. While the GTP binding site is structurally and evolutionarily conserved, the overall GTase mechanism in mammalian and yeast systems differs somewhat. Experiments are underway to crystallize complexes of human GTase with CTD and RNA as well as GTP. Protein engineering is being applied in an effort to crystallize the full length human CE. CAPER co-localizes with splicing factor SC35 in breast cancer cells, as seen by immunofluorescence and confocal microscopy. 13
Publications: Fan, G., Simmons, M.J., Ge, S., Dutta-Simmons, J., Kucharczak, J..F, Ron, Y., Weissmann, D., Chen, C.C., Mukherjee, C., White, E. and Gélinas, C. Defective ubiquitin-mediated degradation of anti-apoptotic Bfl-1 predisposes to lymphoma. Blood 2010 115: 3559-3569. Guo, J.Y., Chen, H-Y, Mathew, R., Fan, J., Strohecker, A.M., Kamphorst, J.J., Chen, G., Lemmons, J.M.S., Karantza, V., Coller, H.A., DiPaola, R.S., Gélinas, C., Rabinowitz, J.D. and White, E.) Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes & Dev. 2011 25: 460-470. 14
Page 1: CENTER FOR ADVANCED BIOTECHNOLOGY A
Page 4 and 5: Director’s Overview CABM—25 and
Page 6 and 7: of Health, National Science Foundat
Page 8 and 9: Cell & Developmental Biology Labora
Page 10 and 11: protein metabolism/activity, such t
Page 12 and 13: Dr. Céline Gélinas CABM Resident
Page 16 and 17: Dr. Masayori Inouye CABM Resident F
Page 18 and 19: Xu, Z., Mirochnitchenko, O., Xu, C.
Page 20 and 21: Dr. Fang Liu CABM Resident Faculty
Page 22 and 23: Publications: Matsuura, I., Chiang,
Page 24 and 25: In the prior year, we have made con
Page 26 and 27: Dr. James Millonig CABM Resident Fa
Page 28 and 29: We have mapped 5 different vl modif
Page 30 and 31: Dr. Arnold Rabson Director Child He
Page 32 and 33: Publications: Zheng, X., Cui, X.X.,
Page 34 and 35: polymerase II, facilitating the sel
Page 36 and 37: Dr. Mengqing Xiang CABM Resident Fa
Page 38 and 39: neurons diminish while there is a s
Page 40 and 41: Laboratory Faculty Director Structu
Page 42 and 43: Human transcription factors are typ
Page 44 and 45: atomic detail and have yielded nume
Page 46 and 47: Figure from Das et al., 2011 showin
Page 48 and 49: Dr. Helen M. Berman Board of Govern
Page 50 and 51: Dr. Chenghua Shao Research Associat
Page 52 and 53: Dr. Joseph Marcotrigiano CABM Resid
Page 54 and 55: The long-term goals of our studies
Page 56 and 57: s Publications: Singarapu, K.K., Mi
Page 58 and 59: Zhao, L., Zhao, K., Hurst, R., Slat
Page 60 and 61: Acton, T.B., Xiao, R., Anderson, S.
Page 62 and 63: Kryshtafovych, A., Bartual, S.G., B
Page 64 and 65:
properties by lowering susceptibili
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Dr. Ann M. Stock Associate Director
Page 68 and 69:
Publications: Barbieri, C.M., Mack,
Page 70 and 71:
Lectures and Seminars 69
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CABM RETREAT, June 30, 2011 Cook Ca
Page 75 and 76:
25 th Anniversary CABM Symposium Fr
Page 77 and 78:
Edery Lab Joseph Albistur George Gh
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PATENTS P. Lobel, et al. “Methods
Page 81 and 82:
Montelione, G.T., Ma, L. and Krug,
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Outside Academic Members Dr. Wayne
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Former CABM Scientific Advisory Boa
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Fiscal Information 86
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Anderson, Stephen Rutgers CABM Gran
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Leukemia & Lymphoma Society BFL-1 a
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Total Award Start - End FY 2011 Dir
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Department of Defense Tumor suppres
Page 97 and 98:
Total Award Start - End FY 2011 Dir
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