The Much Maligned Tick: Key to a New Class of Antibiotics?

Yale researchers have discovered a glycoprotein in ticks (Ixodidae) that kicks in during winter to protect them from the cold also fights infection.  This protein may be the key to a new class of an antibiotics to help  in the battle against dangers pathogens such as MRSA.
Read more at: http://phys.org/news/2014-10-protein-infection.html#jCp

Recommended Readings: Diane Mathis, Ph.D.

Friday Lecture Series

The Ernst A.H. Friedheim Memorial Lecture

Aire, a Transcriptional Regulator Critical for Immunological Tolerance

Diane Mathis, Ph.D., professor, division of immunology,

department of microbiology and immunobiology, Harvard Medical School

March 21, 2014

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

Caspary Auditorium

Recommended Readings

Abramson, J., Giraud, M., Benoist, C., & Mathis, D. (2010). Aire’s partners in the molecular control of immunological tolerance. Cell, 140(1), 123-135

Burzyn, D., Benoist, C., & Mathis, D. (2013). Regulatory T cells in nonlymphoid tissues. Nature Immunology, 14(10), 1007-1013

D’Alise, A. M., Ergun, A., Hill, J. A., Mathis, D., & Benoist, C. (2011). A cluster of coregulated genes determines TGF-β – induced regulatory T-cell (treg) dysfunction in NOD mice. Proceedings of the National Academy of Sciences of the United States of America, 108(21), 8737-8742

Fu, W., Ergun, A., Lu, T., Hill, J. A., Haxhinasto, S., Fassett, M. S., . . . Benoist, C. (2012). A multiply redundant genetic switch ‘locks in’ the transcriptional signature of regulatory T cells. Nature Immunology, 13(10), 972-980

Giraud, M., Yoshid, H., Abramson, J., Rahl, P. B., Young, R. A., Mathis, D., & Benoist, C. (2012). Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells. Proceedings of the National Academy of Sciences of the United States of America, 109(2), 535-540

Koh, A. S., Kingston, R. E., Benoist, C., & Mathis, D. (2010). Global relevance of aire binding to hypomethylated lysine-4 of histone-3. Proceedings of the National Academy of Sciences of the United States of America, 107(29), 13016-13021

Yang, S., Bansal, K., Lopes, J., Benoist, C., & Mathis, D. (2013). Aire’s plant homeodomain(PHD)-2 is critical for induction of immunological tolerance. Proceedings of the National Academy of Sciences of the United States of America, 110(5), 1833-1838

 

Recommended Readings: Michael Strand, Ph.D.

Friday Lecture Series

Polydnaviruses: Viral Mutualists and Nature’s Genetic Engineers

Michael Strand, Ph.D., Regents Professor, department of entomology,

University of Georgia

February 21, 2014

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

Caspary Auditorium

Recommended Readings

Beck, M. H., & Strand, M. R. (2007). A novel polydnavirus protein inhibits the insect prophenoloxidase activation pathway. Proceedings of the National Academy of Sciences of the United States of America, 104(49), 19267-19272

Burke, G. R., Thomas, S. A., Eum, J. H., & Strand, M. R. (2013). Mutualistic polydnaviruses share essential replication gene functions with pathogenic ancestors. PLoS Pathogens, 9(5)

Strand, M. R., & Burke, G. R. (2012). Polydnaviruses as symbionts and gene delivery systems. PLoS Pathogens, 8(7), 5

Thoetkiattikul, H., Beck, M. H., & Strand, M. R. (2005). Inhibitor κB-like proteins from a polydnavirus inhibit NF-κB activation and suppress the insect immune response. Proceedings of the National Academy of Sciences of the United States of America, 102(32), 11426-11431

Webb, B. A., Strand, M. R., Dickey, S. E., Beck, M. H., Hilgarth, R. S., Barney, W. E., . . . Witherell, R. A. (2006). Polydnavirus genomes reflect their dual roles as mutualists and pathogens. Virology, 347(1), 160-174

 

Recommended Readings: Max Cooper, M.D.

Friday Lecture Series

How Did Our Adaptive Immune System Evolve?

Max Cooper, M.D., professor, Emory Vaccine Center and Emory Center for AIDS Research, Emory University School of Medicine

January 31, 2014

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

Caspary Auditorium

Recommended Readings

Alder, M. N., Rogozin, I. B., Iyer, L. M., Glazko, G. V., Cooper, M. D., & Pancer, Z. (2005). Immunology: Diversity and function of adaptive immune receptors in a jawless vertebrate. Science, 310(5756), 1970-1973

Cooper, M. D. (2010). A life of adventure in immunobiology. Annual Review of Immunology 28, 11-19

Cooper, M. D., & Herrin, B. R. (2010). How did our complex immune system evolve? Nature Reviews Immunology, 10(1), 2-3

Guo, P., Hirano, M., Herrin, B. R., Li, J., Yu, C., Sadlonova, A., & Cooper, M. D. (2009). Dual nature of the adaptive immune system in lampreys. Nature, 459(7248), 796-801

Hirano, M., Das, S., Guo, P., & Cooper, M. D. (2011). The evolution of adaptive immunity in vertebrates. Advances in Immunology 109, pp. 125-157

Pancer, Z., & Cooper, M. D. (2006). The evolution of adaptive immunity. Annual Review of Immunology 24 , pp. 497-518

 

Recommended Readings: Poornima Parameswaran Ph.D. February 10

SPECIAL SEMINAR
Monday, February 10, 2014
4:00 p.m., Carson Family Auditorium

Poornima Parameswaran, Ph.D.

Postdoctoral Research Fellow
School of Public Health
University of California, Berkeley

Virome & Immunome Diversity in Dengue & other Infectious Diseases

Recommended Readings:

Empirical Papers

Parameswaran, P., Charlebois, P., Tellez, Y., Nunez, A., Ryan, E. M., Malboeuf, C. M., … Henn, M. R. (2012). Genome-wide patterns of intrahuman dengue virus diversity reveal associations with viral phylogenetic clade and interhost diversity. Journal of Virology, 86(16), 8546–8558. doi:10.1128/JVI.00736-12

Parameswaran, P., Liu, Y., Roskin, K. M., Jackson, K. K. L., Dixit, V. P., Lee, J.-Y., … Fire, A. Z. (2013). Convergent antibody signatures in human dengue. Cell Host & Microbe, 13(6), 691–700. doi:10.1016/j.chom.2013.05.008

Parameswaran, P., Sklan, E., Wilkins, C., Burgon, T., Samuel, M. a, Lu, R., … Fire, A. Z. (2010). Six RNA viruses and forty-one hosts: viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems. PLoS pathogens, 6(2), e1000764. doi:10.1371/journal.ppat.1000764

Review Articles

Fontana, J. M., Alexander, E., & Salvatore, M. (2012). Translational research in infectious disease: current paradigms and challenges ahead. Translational Research, 159(6), 430–453. doi:10.1016/j.trsl.2011.12.009

Wylie, K. M., Weinstock, G. M., & Storch, G. a. (2012). Emerging view of the human virome. Translational Research, 160(4), 283–290. doi:10.1016/j.trsl.2012.03.006

Recommended Readings: Dan R. Littman, M.D., Ph.D.

Friday Lecture Series

Shaping of the Systemic Immune Repertoire by the Intestinal Microbiota

Dan R. Littman, M.D., Ph.D., Helen L. and Martin S. Kimmel Professor of Molecular

Immunology; professor of pathology and microbiology, program in molecular pathogenesis,

Skirball Institute of Biomolecular Medicine, New York University Medical Center;

investigator, Howard Hughes Medical Institute

December 20, 2013

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

Caspary Auditorium

Recommended Readings

Diehl, G. E., Longman, R. S., Zhang, J. -., Breart, B., Galan, C., Cuesta, A., . . . Littman, D. R. (2013). Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX 3 CR1 hi cells. Nature, 494(7435), 116-120

Honda, K., & Littman, D. R. (2012). The microbiome in infectious disease and inflammation. Annual Review of Immunology,  30 , pp. 759-795

Hooper, L. V., Littman, D. R., & Macpherson, A. J. (2012). Interactions between the microbiota and the immune system. Science, 336(6086), 1268-1273

Kinnebrew, M. A., Buffie, C. G., Diehl, G. E., Zenewicz, L. A., Leiner, I., Hohl, T. M., . . . Pamer, E. G. (2012). Interleukin 23 production by intestinal CD103 +CD11b + dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity, 36(2), 276-287

Littman, D. R., & Pamer, E. G. (2011). Role of the commensal microbiota in normal and pathogenic host immune responses. Cell Host and Microbe, 10(4), 311-323

 

Recommended Readings: David Artis, Ph.D. Monday, Oct. 14, 2013

SPECIAL SEMINAR

Regulation of Barrier Immunity

 David Artis, Ph.D.

Associate Professor of Microbiology

 Perelman School of Medicine

University of Pennsylvania

Monday, October 14, 2013

4:00 p.m., Carson Family Auditorium

Recommended Review:

Saenz, Steven A.; Taylor, Betsy C.; Artis, David. 2008.  Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites .   IMMUNOLOGICAL REVIEWS  226: 172-190  

Artis, David.  2008.  Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut.  NATURE REVIEWS IMMUNOLOGY   8(6):411-420   DOI: 10.1038/nri2316

Recommended Readings:

Saenz, Steven A.; Siracusa, Mark C.; Monticelli, Laurel A.; et al. 2013. IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells .    JOURNAL OF EXPERIMENTAL MEDICINE.  210(9): 1823-1837   DOI: 10.1084/jem.20122332

Philip, Naomi H.; Artis, David. 2013. New friendships and old feuds: relationships between innate lymphoid cells and microbial communities.   IMMUNOLOGY AND CELL BIOLOGY.   91(3):225-231   DOI: 10.1038/icb.2013.2

Tomasello, Elena; Bedoui, Sammy.  2013. Intestinal innate immune cells in gut homeostasis and immunosurveillance.   IMMUNOLOGY AND CELL BIOLOGY   91(3): 201-203   DOI: 10.1038/icb.2012.85

Goto, Yoshiyuki; Ivanov, Ivaylo I.  2013.  Intestinal epithelial cells as mediators of the commensal-host immune crosstalk.   IMMUNOLOGY AND CELL BIOLOGY.  91(3):204-214   DOI: 10.1038/icb.2012.80

Monticelli, Laurel A.; Sonnenberg, Gregory F.; Artis, David. 2012.   Innate lymphoid cells: critical regulators of allergic inflammation and tissue repair in the lung.   CURRENT OPINION IN IMMUNOLOGY   24(3):284-289   DOI: 10.1016/j.coi.2012.03.012

Artis, D.; Grencis, R. K.  2008. The intestinal epithelium: sensors to effectors in nematode infection.  MUCOSAL IMMUNOLOGY .  1(4): 252-264   DOI: 10.1038/mi.2008.21

 

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: 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