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Dr.David Baltimore:1975 Recipient of Nobel Prize in Physiology or Medicine PDF Print E-mail
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Sunday, 15 November 2009 00:29

Our laboratory is involved in three major directions of research.

The first is study of the remarkable range of activity of the NF-kB transcription factor. It activates perhaps 1000 genes in response to a wide range of stimuli. It has different physiologic roles in different cells. How one factor can be so varied in its activity is the puzzle that interests us. We are studying this at the level of DNA-protein interactions as well as signal transduction pathways. We are studying its role in normal cells and in diseases like cancer and AIDS.

 The second line of work involves using gene transfer methods to reprogram the immune system. We have shown that we can design a retrovirus vector able to express cDNA’s encoding both chains of the T cell receptor (TCR) protein. When mouse hematopoietic stem cells are transduced with the vector and then inoculated into irradiated mice, many of the resulting T cells express the TCR encoded by the vector. We have shown that when the TCR is able to recognize specific peptides from a tumor antigen, the animal can reject tumors carrying the antigen. We plan to extend these studies to human tumor antigens with the goal of developing a human therapy. We are also studying whether the same strategy will work for antibody gene expression by B cells with a goal of devising a new therapy for AIDS.

The third goal of the laboratory is to understand the role of the Ryk protein as a co-receptor for Wnt proteins. We have shown that Wnt interacts with both Ryk and Frizzled surface receptor proteins in a tripartite complex. We are now investigating the pathways activated by Ryk and the role of Ryk in neuronal guidance.

Biography:

David L. Baltimore (born 7 March 1938) is an American biologist, university administrator, and Nobel laureate in Physiology or Medicine. He served as president of the California Institute of Technology (Caltech) from 1997 to 2006, and is currently the Robert A. Millikan Professor of Biology at Caltech. He also served as president of Rockefeller University from 1990 to 1991, and was president of the American Association for the Advancement of Science in 2007. As is traditional in the AAAS, he now serves as the Chairman of the Board of Directors.

 

Research:

NF-kappaB

The NF-kappaB transcription factor is involved in many signaling pathways. These pathways include those associated with inflammatory response, immunity, cancer, and memory and learning.

HIV

NF-kappaB and other proteins are involved as critical factors for expression of the HIV genome. These proteins and their binding sites will be studied.

T Cell Memory

T cell memory involves the generation and maintenance of T cells that retain a record of previous immune responses. The molecular mechanisms that mediate these activities remain uncertain.

Other Work

Other work in the lab includes other signaling pathway molecules such as Wnt and frizzled.

Selected Publications:

2008

Ziegler, L., et al., Targeting Lentiviral Vectors to Antigen-Specific Immunoglobulins. Hum Gene Ther, 2008.

Werner, S.L., et al., Encoding NF-{kappa}B temporal control in response to TNF: distinct roles for the negative regulators I{kappa}B{alpha} and A20. Genes Dev, 2008. 22(15): p. 2093-101.

O'Connell, R.M., et al., Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med, 2008. 205(3): p. 585-94.          
    
Baltimore, D., et al., MicroRNAs: new regulators of immune cell development and function. Nat Immunol, 2008. 9(8): p. 839-45.          
    
Baltimore, D., Vaccine trial provided valuable information. Nature, 2008. 452(7189): p. 811.           
    
Schatz, D. G., M. A. Oettinger, et al. (2008). "Pillars article: the V(D)J recombination activating gene, RAG-1. 1989." J Immunol 180(1): 5-18.
         
Yang, L., H. Yang, et al. (2008). "Engineered lentivector targeting of dendritic cells for in vivo immunization." Nat Biotechnol.          
    
Baltimore, D. (2008). "Science for the globe." Science 319(5864): 697.
O'Connell, R. M., D. S. Rao, et al. (2008). "Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder." J Exp Med.

2007

An, D. S., R. E. Donahue, et al. (2007). "Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates." Proc Natl Acad Sci U S A 104(32): 13110-5.
         
Taganov, K.D., M.P. Boldin, and D. Baltimore, MicroRNAs and immunity: tiny players in a big field. Immunity, 2007. 26(2): p. 133-7.          

O'Connell, R.M., et al., MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A, 2007. 104(5): p. 1604-9.

2006

Sen, R. and D. Baltimore, Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 1986. 46: 705-716. J Immunol, 2006. 177(11): p. 7485-96.            
    
Taganov, K.D., et al., NF-{kappa}B-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A, 2006. 103(33): p. 12481-6.          
    
Yang, L., et al., Targeting lentiviral vectors to specific cell types in vivo. Proc Natl Acad Sci U S A, 2006. 103(31): p. 11479-84.          
    
Hoffmann, A. and D. Baltimore, Circuitry of nuclear factor kappaB signaling. Immunol Rev, 2006. 210: p. 171-86.

2005

Covert, M.W., et al., Achieving stability of lipopolysaccharide-induced NF-kappaB activation. Science, 2005. 309(5742): p. 1854-7.            
    
Baltimore, D., An interview with David Baltimore. [Interview by Joseph Glorioso and Jenny Jacoby]. Gene Ther, 2005. 12(17): p. 1291-3.           

Meffert, M. K., and Baltimore, D. (2005). Physiological functions for brain NF-kappaB. Trends Neurosci 28, 37-43.           

Yang, L. and D. Baltimore, Long-term in vivo provision of antigen-specific T cell immunity by programming hematopoietic stem cells. Proc Natl Acad Sci U S A, 2005. 102(12): p. 4518-23.

 

 
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