The State of Vaccine Development: Toughest Problems Remain Unsolved

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.

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Breakthrough Science: Cancer Immunotherapy – a new “One-Two” Punch SIRPalpha

 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.

 

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Recommended Readings: Jeffrey M. Friedman, M.D., Ph.D. May 20, 2013

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.

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Recommended Readings: Richard A. Young, Ph.D.

Friday Lecture Series

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

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

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

 

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Recommended Readings:Detlev Arendt, Ph.D.

Friday Lecture Series

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

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

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

 

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Recommended Readings: Alexander Varshavsky, Ph.D.

Friday Lecture Series

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

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

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

 

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Recommended Readings: Robert H. Singer, Ph.D.

Friday Lecture Series

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

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

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

 

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Recommended Readings: Erin Schuman, Ph.D.

Friday Lecture Series

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

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

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

 

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Recommended Readings: Edward A. Fisher, M.D., Ph.D., M.P.H.

Friday Lecture Series

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

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

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

 

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Recommended Readings: Maria M. Mota PhD March 13, 2013

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

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