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.
Monday Lecture Series
To Eat or Not To Eat: Studies of a Complex Motivational Behavior
Jeffrey M. Friedman, M.D. , Ph.D.
Marilyn M. Simpson Professor, Laboratory of Molecular Genetics
Investigator, Howard Hughes Medical Institute
Carson Family Auditorium, CRC
4:00 p.m., Refreshments 3:45
Recommended Readings:
L Domingos, Ana I.; Vaynshteyn, Jake; Voss, Henning U.; et al. 2011. Leptin regulates the reward value of nutrient. NATURE NEUROSCIENCE . 14(12):1562-U92 DOI: 10.1038/nn.2977
Scott, Michael M.; Lachey, Jennifer L.; Sternson, Scott M.; et al. 2009. Leptin Targets in the Mouse Brain. JOURNAL OF COMPARATIVE NEUROLOGY. 514(5): 518-532 DOI: 10.1002/cne.22025
Adam, Tanja C.; Epel, Elissa S. 2007. Stress, eating and the reward system. Annual Meeting of the Society-for-the-Study-of-Ingestive-Behavior. Location: Naples, Florida, JUL 18-22, 2006. Society for the Study of Ingestive Behavior. PHYSIOLOGY & BEHAVIOR. 91(4, Sp. Issue SI): 449-458 DOI: 10.1016/j.physbeh.2007.04.011
Heisler, Lora K.; Jobst, Erin E.; Sutton, Gregory M.; et al 2006. Serotonin reciprocally regulates melanocortin neurons to modulate food intake. NEURON. 51(2): 239-249 DOI: 10.1016/j.neuron.2006.06.004
Alon, T; Friedman, JM. 2006. Late-onset leanness in mice with targeted ablation of melanin concentrating hormone neurons. JOURNAL OF NEUROSCIENCE . 26(2): 389-397 DOI: 10.1523/JNEUROSCI.1203-05.2006
Figlewicz, DP; Bennett, J; Evans, SB; et al. 2004. Intraventricular insulin and leptin reverse place preference conditioned with high-fat diet in rats. BEHAVIORAL NEUROSCIENCE . 118(3): 479-487 DOI: 10.1037/0735-7044.118.3.479 REQUEST ARTICLE FROM MARKUS LIBRARY
Pinto, S; Roseberry, AG; Liu, HY; et al. 2004. Rapid rewiring of arcuate nucleus feeding circuits by leptin. SCIENCE . 304(5667): 110-115 DOI: 10.1126/science.
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
Transcriptomes and Proteomes at Synapses
Erin Schuman, Ph.D., director, department of synaptic plasticity, and professor,
Max Planck Institute for Brain Research
March 22, 2012
Recommended Readings
Bingol, B., & Schuman, E. M. (2005). Synaptic protein degradation by the ubiquitin proteasome system. Current Opinion in Neurobiology, 15(5), 536-541
Sutton, M. A., & Schuman, E. M. (2006). Dendritic protein synthesis, synaptic plasticity, and memory. Cell, 127(1), 49-58
Sutton, M. A., & Schuman, E. M. (2005). Local translational control in dendrites and its role in long-term synaptic plasticity. Journal of Neurobiology, 64(1), 116-131
Sutton, M. A., & Schuman, E. M. (2009). Partitioning the synaptic landscape: Distinct microdomains for spontaneous and spike-triggered neurotransmission. Science Signaling, 2(65)
Tai, H. -., & Schuman, E. M. (2008). Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction. Nature Reviews Neuroscience, 9(11), 826-838
The Regression of Atherosclerosis and its Molecular Regulation: Insights from Novel Mouse Models
Genetics of Lipid Disorders and Atherosclerosis: A Symposium in Honor of Jan Breslow’s 70th Birthday
Edward A. Fisher, M.D., Ph.D., M.P.H.,
Leon Charney Professor of CardiovascularMedicine, director, Center for the Prevention of Cardiovascular Disease and director,
Marc and Ruti Bell Program in Vascular Biology,
New York University School of Medicine
March 15, 2012
Recommended Readings
Amirbekian, V., Aguinaldo, J. G. S., Amirbekian, S., Hyafil, F., Vucic, E., Sirol, M., . . . Fayad, Z. A. (2009). Atherosclerosis and matrix metalloproteinases: Experimental molecular MR imaging in vivo. Radiology, 251(2), 429-438
Cormode, D. P., Chandrasekar, R., Delshad, A., Briley-Saebo, K. C., Calcagno, C., Barazza, A., . . . Fayad, Z. A. (2009). Comparison of synthetic high density lipoprotein (HDL) contrast agents for MR imaging of atherosclerosis. Bioconjugate Chemistry, 20(5), 937-943
Fayad, Z. A. (2010). Atherosclerotic plaque composition: Analysis with multicolor CT and targeted gold nanoparticles. Radiology, 256(3), 774-782
Feig, J. E., Rong, J. X., Shamir, R., Sanson, M., Vengrenyuk, Y., Liu, J., . . . Fisher, E. A. (2011). HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells. Proceedings of the National Academy of Sciences of the United States of America, 108(17), 7166-7171
Parathath, S., Grauer, L., Huang, L. -., Sanson, M., Distel, E., Goldberg, I. J., & Fisher, E. A. (2011). Diabetes adversely affects macrophages during atherosclerotic plaque regression in mice. Diabetes, 60(6), 1759-1769
Van Gils, J. M., Derby, M. C., Fernandes, L. R., Ramkhelawon, B., Ray, T. D., Rayner, K. J., . . . Moore, K. J. (2012). The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques. Nature Immunology, 13(2), 136-143
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
