Alfred Singer, M.D.

Senior Investigator

Experimental Immunology Branch


Building 10, Room 4B36
Bethesda, MD 20892


Research Topics

Lymphocyte Development

The differentiation of immature CD4+8+ (double positive, DP) thymocytes into mature T cells is the key event in T cell development as it gives rise to functional T cells and determines the mature T cell repertoire. Our research seeks to elucidate the molecular mechanism by which thymic selection generates an MHC-restricted T cell receptor repertoire that is coordinated with CD4 and CD8 coreceptor expression and appropriate T cell function.


Dr. Singer received his M.D. from Columbia University and his clinical training at the Columbia-Presbyterian Medical Center. He was a fellow in immunology at the Rockefeller University before coming to the NCI. He is chief of the Experimental Immunology Branch and his research interests are in lymphocyte recognition and development, especially the molecular and cellular recognition signals that result in self/nonself discrimination during early development.

Selected Publications

  1. 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. 2013;38(6):1116-28.

  2. 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. 2013;154(6):1326-41.

  3. Pobezinsky LA, Angelov GS, Tai X, Jeurling S, Van Laethem F, Feigenbaum L, Park JH, Singer A. Clonal deletion and the fate of autoreactive thymocytes that survive negative selection. Nat Immunol. 2012;13(6):569-78.

  4. Park JH, Adoro S, Guinter T, Erman B, Alag AS, Catalfamo M, Kimura MY, Cui Y, Lucas PJ, Gress RE, Kubo M, Hennighausen L, Feigenbaum L, Singer A. Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells. Nat Immunol. 2010;11(3):257-64.

  5. Brugnera E, Bhandoola A, Cibotti R, Yu Q, Guinter TI, Yamashita Y, Sharrow SO, Singer A. Coreceptor reversal in the thymus: signaled CD4+8+ thymocytes initially terminate CD8 transcription even when differentiating into CD8+ T cells. Immunity. 2000;13(1):59-71.

This page was last updated on September 12th, 2018