Alfred Singer

Alfred Singer (born December 10, 1946) is an American immunologist who works at the National Institutes of Health (NIH), where he is the Chief of the Experimental Immunology Branch of the National Cancer Institute (NCI) Center for Cancer Research. He is best known for his work regarding lymphocyte development, particularly the differentiation of immature CD4+8+ (double positive) thymocytes into mature T cells. Singer's work is foundational in the understanding of T cells and MHC-restricted antigen recognition.

Singer's work explores the mechanisms with which a body identifies what is self and what is not self. At a time when many researchers understood that T cells recognize self through identification of the major histocompatibility complex (MHC) it was not understood how T cells acquire that capability. Using a unique approach to thymus transplantation, Singer showed that it is the thymus that educates self-recognition specificity in T cells. A series of later studies in Singer's lab demonstrated that the property of self-recognition in T cells is acquired during development in the thymus rather than predetermined prior to development or genetically encoded in the genome. Tai X, Erman B, Alag A, Mu J, Kimura M, Katz G, Guinter T, McCaughtry T, Etzensperger R, Feigenbaum L, Singer DS, Singer A: Foxp3 transcription factor is proapoptotic and lethal to developing regulatory T cells unless counterbalanced by cytokine survival signals. Immunity. 38: 1116–28, 2013. Kimura MY, Pobezinsky LA, Guinter TI, Thomas J, Adams A, Park JH, Tai X, Singer A: IL-7 signaling must be intermittent, not continuous, during CD8+ T cell homeostasis to promote cell survival instead of cell death. Nature Immunology. 14: 143–51, 2013. Van Laethem F, Tikhonova AN, Pobezinsky LA, Tai X, Kimura MY, Le Saout C, Guinter TI, Adams A, Sharrow SO, Bernhardt G, Feigenbaum L, Singer A: Lck availability during thymic selection determines the recognition specificity of the T cell repertoire. Cell. 154: 1326–41, 2013. SInger A, Adoro S, Park JH: Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nature Reviews Immunology. 2008 Oct; 8(10): 788–801. doi 10.1038/nri2416.