Accelerating Next-Generation Vaccine Development for Global Disease Prevention
Koff, W. C. et all Science v. 340, 2013
Recent technological advances in molecular genetics, molecular and cellular immunology, structural biology, bioinformatics, computational biology, nanotechnology, formulation methods, and systems biology are ushering in a new era of discovery. However, translation of these advances into vaccines remains impeded by major gaps in our knowledge of human immune responses.
Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer
K. Weiskoff et al. ScienceExpress May 31, 2013
AntibodiesCD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist. We engineered high-affinity SIRPα variants with approximately 50,000-fold increased affinity for human CD47 relative to wild-type SIRPα. As high-affinity SIRPα monomers, they potently antagonized CD47 on cancer cells but did not induce macrophage phagocytosis on their own. Instead, they exhibited remarkable synergy with all tumor-specific monoclonal antibodies tested by increasing phagocytosis in vitro and enhancing antitumor responses in vivo. This “one-two punch” directs immune responses against tumor cells while lowering the threshold for macrophage activation, thereby providing a universal method for augmenting the efficacy of therapeutic anticancer antibodies.
Cancer Biology Lecture
Transcriptional Control of Cell Identity
Richard A. Young, Ph.D., professor of biology and member,
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
May 17, 2013
Recommended Readings
Guenther, M. G., & Young, R. A. (2010). Repressive transcription. Science, 329(5988), 150-151
Jaenisch, R., & Young, R. (2008). Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell, 132(4), 567-582
Mazzoni, E. O., Mahony, S., Iacovino, M., Morrison, C. A., Mountoufaris, G., Closser, M., . . . Wichterle, H. (2011). Embryonic stem cell-based mapping of developmental transcriptional programs. Nature Methods, 8(12), 1056-1060
Newman, J. J., & Young, R. A. (2010). Connecting transcriptional control to chromosome structure and human disease. Cold Spring Harbor Symposia on Quantitative Biology 75 , pp. 227-235
Novershtern, N., Subramanian, A., Lawton, L. N., Mak, R. H., Haining, W. N., McConkey, M. E., . . . Ebert, B. L. (2011). Densely interconnected transcriptional circuits control cell states in human hematopoiesis. Cell, 144(2), 296-309
Young, R. A. (2011). Control of the embryonic stem cell state. Cell, 144(6), 940-954
The Evolutionary Origin of the Vertebrate Brain
Detlev Arendt, Ph.D., honorary professor, University of Heidelberg, Germany;
group leader and senior scientist, European Molecular Biology Laboratory
May 3, 2013
Recommended Readings
Arendt, D., Tessmar-Raible, K., Snyman, H., Dorresteijn, A. W., & Wittbrodf, J. (2004). Ciliary photoreceptors with a vertebrate-type opsin in an invertebrate brain. Science, 306(5697), 869-871
Christodoulou, F., Raible, F., Tomer, R., Simakov, O., Trachana, K., Klaus, S., . . . Arendt, D. (2010). Ancient animal microRNAs and the evolution of tissue identity. Nature, 463(7284), 1084-1088
Raible, F., Tessmar-Raible, K., Osoegawa, K., Wincker, P., Jubin, C., Balavoine, G., . . . Arendt, D. (2005). Evolution: Vertebrate-type intron-rich genes in the marine annelid platynereis dumerilii. Science, 310(5752), 1325-1326
Tessmar-Raible, K., & Arendt, D. (2003). Emerging systems: Between vertebrates and arthropods, the lophotrochozoa. Current Opinion in Genetics and Development, 13(4), 331-340
Tomer, R., Denes, A. S., Tessmar-Raible, K., & Arendt, D. (2010). Profiling by image registration reveals common origin of annelid mushroom bodies and vertebrate pallium. Cell, 142(5), 800-809
William H. Stein Memorial Lecture
Recent Discoveries about the Ubiquitin System and the N-end Rule Pathway
Alexander Varshavsky, Ph.D.,
Howard and Gwen Laurie Smits Professor of Cell Biology,
California Institute of Technology
April 26, 2012
Recommended Readings
Graciet, E., Walter, F., Maoiléidigh, D. Ó., Pollmann, S., Meyerowitz, E. M., Varshavsky, A., & Wellmer, F. (2009). The N-end rule pathway controls multiple functions during arabidopsis shoot and leaf development. Proceedings of the National Academy of Sciences of the United States of America, 106(32), 13618-13623
Hwang, C. -., Shemorry, A., Auerbach, D., & Varshavsky, A. (2010). The N-end rule pathway is mediated by a complex of the RING-type Ubr1 and HECT-type Ufd4 ubiquitin ligases. Nature Cell Biology, 12(12), 1177-1185
Hwang, C. -., Shemorry, A., & Varshavsky, A. (2010). N-terminal acetylation of cellular proteins creates specific degradation signals. Science, 327(5968), 973-977
Hwang, C. -., Shemorry, A., & Varshavsky, A. (2009). Two proteolytic pathways regulate DNA repair by cotargeting the Mgt1 alkylguanine transferase. Proceedings of the National Academy of Sciences of the United States of America, 106(7), 2142-2147
Varshavsky, A. (2006). The early history of the ubiquitin field. Protein Science, 15(3), 647-654
Varshavsky, A. (2011). The N-end rule pathway and regulation by proteolysis. Protein Science, 20(8), 1298-1345
Xia, Z., Webster, A., Du, F., Piatkov, K., Ghislain, M., & Varshavsky, A. (2008). Substrate-binding sites of UBR1, the ubiquitin ligase of the N-end rule pathway. Journal of Biological Chemistry, 283(35), 24011-24028
Following Single mRNAs from Birth to Death
Robert H. Singer, Ph.D., professor and co-chair,
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine
April 12, 2012
Recommended Readings
Ben-Ari, Y., Brody, Y., Kinor, N., Mor, A., Tsukamoto, T., Spector, D. L., . . . Shav-Tal, Y. (2010). The life of an mRNA in space and time. Journal of Cell Science, 123(10), 1761-1774
Darzacq, X., Yao, J., Larson, D. R., Causse, S. Z., Bosanac, L., De Turris, V., . . . Singer, R. H. (2009). Imaging transcription in living cells . Annual Review of Biophysics 38 (1) , pp. 173-196
Grünwald, D., & Singer, R. H. (2010). In vivo imaging of labelled endogenous Β-actin mRNA during nucleocytoplasmic transport. Nature, 467(7315), 604-607
Katz, Z. B., Wells, A. L., Park, H. Y., Wu, B., Shenoy, S. M., & Singer, R. H. (2012). β-Actin mRNA compartmentalization enhances focal adhesion stability and directs cell migration. Genes and Development, 26(17), 1885-1890
Lionnet, T., Czaplinski, K., Darzacq, X., Shav-Tal, Y., Wells, A. L., Chao, J. A., . . . Singer, R. H. (2011). A transgenic mouse for in vivo detection of endogenous labeled mRNA. Nature Methods, 8(2), 165-170
Park, H. Y., Buxbaum, A. R., & Singer, R. H. (2010). Single mRNA tracking in live cells. Methods in Enzymology, 472, 387-406
Trcek, T., Larson, D. R., Moldón, A., Query, C. C., & Singer, R. H. (2011). Single-molecule mRNA decay measurements reveal promoter-regulated mRNA stability in yeast. Cell, 147(7), 1484-1497
Special Seminar Series
Malaria Infection, Superinfection and Co-infections: From Simple Models to Complex Interactions
Maria M. Mota, PH.D.
Unit Leader, Malaria Unit
Instituto de Medicina Molecular
Monday March 18, 2013
Recommended Readings:
Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; et al. 2012. The Dynamics of Naturally Acquired Immunity to Plasmodium falciparum Infection. PLOS COMPUTATIONAL BIOLOGY. 8(10): e1002729 DOI: 10.1371/journal.pcbi.1002729
Klein, Eili Y.; Smith, David L.; Laxminarayan, Ramanan; et al. 2012. Superinfection and the evolution of resistance to antimalarial drugs. PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES. 279( 1743):3834-3842 DOI: 10.1098/rspb.2012.1064
Portugal, Silvia; Drakesmith, Hal; Mota, Maria M. 2011. Superinfection in malaria: Plasmodium shows its iron will. EMBO REPORTS. 12(12):1233-1242 DOI: 10.1038/embor.2011.213
van Santen, Susanne; de Mast, Quirijn; Swinkels, Dorine W.; et al. 2011. Hepcidin in malaria superinfection: can findings be translated to humans? NATURE MEDICINE. 17(11):1341-1341 DOI: 10.1038/nm.2488
Portugal, Silvia; Carret, Celine; Recker, Mario; et al. 2011. Host-mediated regulation of superinfection in malaria. NATURE MEDICINE. 17(6):732-U126 DOI: 10.1038/nm.2368
Templeton, TJ; Keister, DB; Muratova, O; et al. 1998. Adherence of erythrocytes during exflagellation of Plasmodium falciparum microgametes is dependent on erythrocyte surface sialic acid and glycophorins. JOURNAL OF EXPERIMENTAL MEDICINE. 187(10 ):1599-1609 DOI: 10.1084/jem.187.10.1599
Extracellular and Intracellular Mechanisms of Synapse Patterning in C. elegans
Kang Shen, Ph.D., M.P.H., associate professor,
department of biological sciences, Stanford University
February 22, 2012
Recommended Readings
Allen, P. B., Sgro, A. E., Chao, D. L., Doepker, B. E., Edgar, J. S., Shen, K., & Chiu, D. T. (2008). Single-synapse ablation and long-term imaging in live C. elegans. Journal of Neuroscience Methods, 173(1), 20-26
Crane, M. M., Stirman, J. N., Ou, C. -., Kurshan, P. T., Rehg, J. M., Shen, K., & Lu, H. (2012). Autonomous screening of C. elegans identifies genes implicated in synaptogenesis. Nature Methods, 9(10), 977-980
Klassen, M. P., Wu, Y. E., Maeder, C. I., Nakae, I., Cueva, J. G., Lehrman, E. K., . . . Shen, K. (2010). An arf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation. Neuron, 66(5), 710-723
Maeder, C. I., & Shen, K. (2011). Genetic dissection of synaptic specificity. Current Opinion in Neurobiology, 21(1), 93-99
Margeta, M. A., Wang, G. J., & Shen, K. (2009). Clathrin adaptor AP-1 complex excludes multiple postsynaptic receptors from axons in C. elegans. Proceedings of the National Academy of Sciences of the United States of America, 106(5), 1632-1637
RNA-mediated Pathways to Disease
Maurice Swanson, Ph.D., associate director, Center for NeuroGenetics,
and professor of molecular genetics and microbiology,
University of Florida College of Medicine
February 15, 2012
Recommended Readings
Daughters, R. S., Tuttle, D. L., Gao, W., Ikeda, Y., Moseley, M. L., Ebner, T. J., . . . Ranum, L. P. W. (2009). RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genetics, 5(8)
Ho, T. H., Savkur, R. S., Poulos, M. G., Mancini, M. A., Swanson, M. S., & Cooper, T. A. (2005). Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy. Journal of Cell Science, 118(13), 2923-2933
Kanadia, R. N., Shin, J., Yuan, Y., Beattie, S. G., Wheeler, T. M., Thornton, C. A., & Swanson, M. S. (2006). Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy. Proceedings of the National Academy of Sciences of the United States of America, 103(31), 11748-11753
Osborne, R. J., Lin, X., Welle, S., Sobczak, K., O’Rourke, J. R., Swanson, M. S., & Thornton, C. A. (2009). Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy. Human Molecular Genetics, 18(8), 1471-1481
Shin, J., Charizanis, K., & Swanson, M. S. (2009). Pathogenic RNAs in microsatellite expansion disease. Neuroscience Letters, 466(2), 99-102
Yuan, Y., Compton, S. A., Sobczak, K., Stenberg, M. G., Thornton, C. A., Griffith, J. D., & Swanson, M. S. (2007). Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs. Nucleic Acids Research, 35(16), 5474-5486
Control of Animal Behavior and Decision Making through TRP Channels
Craig Montell, Ph.D., Duggan Professor,
department of molecular, cellular and developmental biology,
University of California, Santa Barbara
February 8, 2012
Recommended Readings
Kwon, Y., Kim, S. H., Ronderos, D. S., Lee, Y., Akitake, B., Woodward, O. M., . . . Montell, C. (2010). Drosophila TRPA1 channel is required to avoid the naturally occurring insect repellent citronellal. Current Biology, 20(18), 1672-1678
Lee, Y., Moon, S. J., & Montell, C. (2009). Multiple gustatory receptors required for the caffeine response in drosophila. Proceedings of the National Academy of Sciences of the United States of America, 106(11), 4495-4500
Liu, Z., Wang, X., Yu, Y., Li, X., Wang, T., Jiang, H., . . . Smith, W. W. (2008). A drosophila model for LRRK2-linked parkinsonism. Proceedings of the National Academy of Sciences of the United States of America, 105(7), 2693-2698
Montell, C. (2005). The TRP superfamily of cation channels. Science’s STKE [Electronic Resource] : Signal Transduction Knowledge Environment., 2005(272)
Waldo, G. L., Ricks, T. K., Hicks, S. N., Cheever, M. L., Kawano, T., Tsuboi, K., . . . Kendall Harden, T. (2010). Kinetic scaffolding mediated by a phospholipase C-β and G q signaling complex. Science, 330(6006), 974-980
