1. 1. RALPH STEINMAN Presented by: Alden Parker 2/25/15 http://www.scientificamerican.com/article/steinman-nobel-laureate-explains-discovery-dendritic-cells/ http://www.medicineatyale.org/julyaug2006/news/newsarticles/61038
2. 2. BIOGRAPHY Jan 14, 1943 Sep 30, 2011 From Montreal, Qubec, Canada Son of Ashkenazi Jewish Haberdasher, interest in Science began in High School 1963 - B.S. McGill University 1968 - M.D. Harvard Medical School, Learned about Cell Bio/Immunology in Elizabeth Betty Hays Lab 1970 - Residency/Internship Mass. Gen. Hospital met Claudia Hoeffl, married in 1971, 3 children, 3 grandchildren 1971 - Post-Doc Rockefeller University, NYC: Asst. Prof. 1972, Assoc. Prof. 1976, Prof. 1988 1995 - Named Henry Kunkel Professor of Immunology 1998 - Director of Christopher Browne Center for immunology and immune diseases 1999 2011 won many awards for his immunological research http://www.theflagstore.ca/store/shop/sewn-nylon-canadian-flag/ http://06880danwoog.com/2011/10/26/remembering-ralph-steinman/ http://www.anatomy.org/content/elizabeth-hay-photo-gallery
3. 3. EARLY RESEARCH Joined Lab of Cellular Phys. & Immunology headed by Zanvil Cohn and James Hirsch Lab was founded by microbiologist Ren Dubos, who recognized the need to study the host in immunology Think globally. Act Locally. With Cohn, wanted to understand how white cells ID, obtain, and eliminate infectious pathogens and tumor cells Questions: What tells the immune system to respond? How is the immune system so precise in its response to pathogens? http://www.nature.com/nm/journal/v13/n10/fig_tab/nm1643_F2.html
4. 4. MAJOR DISCOVERY, CONTINUED DC RESEARCH Discovered dendritic cells (DCs) in mouse spleen in Zanvil Cohns lab at Rockefeller University in 1973 Distinguished DCs from macrophages by morphological and surface expression characterization of both (DCs not adherent, express MHC-II, no Fc receptors, no phagocytosis) IDd the DC as sentinel for and conduit between innate and adaptive immune responses. Controllers that create and curtail immunity. Displayed that DCs are the main initiators of T-Cell mediated immune responses Most of his findings were not widely accepted until the mid-1990s
5. 5. MORE FINDINGS & THEORIES Took DC findings and applied them to human disease: DC and Immune- based vaccines for graft rejection, tumor resistance, autoimmunity, & pathogen infection. 2010 phase I clinical trial of DC-targeted HIV vaccine Developed DC enrichment from progenitors and IDd DCs in other tissue types Macrophages mediate innate immunity via phagocytosis and intracellular killing Antibodies mediate adaptive immunity by neutralizing microbial toxins DCs integrate innate and adaptive responses
6. 6. DENDRITIC CELL MACROPHAGE Behnsen et al., 2007
7. 7. DEATH Diagnosed with pancreatic cancer in 2007 Self Treatment was based on his own research, lived a relatively healthy life for 4 years after diagnosis! (~95% of diagnosed patients die within 12 months) Piece of his tumor grown in cell culture to produce antigenhis blood used to create DCs against antigen. DCs were charged with RNA from tumor. Used with ~7 other therapies (chemo, surgery, cancer growth inhibitors, etc.) 1 week before 2011 announcement, he joked with his daughter regarding the Nobel Prize, They dont give it to you if you have passed away. I got to hold out for that. Died 3 days before 2011 Nobel Prize announcements
8. 8. 2011 NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE Only recent Nobel Laureate to receive the award posthumously Steinman got , the other was split between Bruce Beutler and Jules Hoffman for discoveries in innate immunity activation (TLRs) http://www.telegraph.co.uk/news/science/science-news/8804713/Nobel-jury-left-red-faced- by-death-of-laureate.html
9. 9. LEGACY Mentored 100+ Post-Docs Published 450 scientific papers Editor of J. Exp. Med. starting in 1978 Advising editor of Hum. Immunol., J. Clin. Immunol., J. Immunol. Met., PNAS Highly supportive of collaboration and interaction between different laboratories Family donated Nobel Prize money to charity and to Steinman scholarship program for young scientists His findings laid the groundwork for new fields of research and novel therapies for human disease, with an array of possibilities moving forward
10. 10. QUESTIONS? http://www.shutterstock.com/video/clip-3645368-stock-footage--x-fullhd-video-hypnotic-turning-spiral-and-a-question-mark-in-the-center.html?src=rel/679765:7/gg
11. 11. REFERENCES http://www.theguardian.com/science/2011/oct/03/nobel-prize-awarded-dead-scientist http://www.scientificamerican.com/article/steinman-nobel-laureate-explains-discovery-dendritic-cells/ http://www.nobelprize.org/nobel_organizations/nobelfoundation/press_releases_archive/2011/steinman.html http://www.pancreatic.org/site/c.htJYJ8MPIwE/b.5050503/k.40C9/Pancreatic_Cancer_Facts.htm Steinman RM & Cohn ZA. (1973). Identification of a novel cell type in peripheral lymphoid organs of mice. J Exp Med. 137; 1142 1162. Steinman RM. (2012). Decisions about dendritic cells: past, present and future. Ann Rev Immunol. 30; 1 22. Steinman RM & Banchereau J. (2007). Taking dendritic cells into medicine. Nature. 449; 419 426. Steinman RM. (2006). Linking innate to adaptice immunity through dendritic cells. Novartis Found Symp. 279; 216 219. Behnsen J, Narang P, Hasenberg M, Gunzer F, et al. (2007). Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans. PLoS Pathogens. 3; 138 151.