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.

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.

 

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.

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