Alfred Singer, M.D.

Alfred Singer, M.D.

  • Center for Cancer Research
  • National Cancer Institute


Dr. Alfred Singer is a renowned immunologist for his work on T cell development, signaling, and selection in the thymus. He received his M.D. from Columbia University, his medical training at the Columbia-Presbyterian Medical Center, and his basic research training at Rockefeller University and the NCI. He and his colleagues established the Experimental Immunology Branch in the NCI with the mission to perform innovative research in basic immunology and he was appointed its Branch Chief. His research focuses on T-lymphocyte recognition and development, especially the molecular and cellular recognition signals that result in self/nonself discrimination, repertoire selection, and self-tolerance. He is recognized for many innovative discoveries that elucidate how the thymus generates functional T cells reactive against foreign antigens while still being self-tolerant. His discoveries include:

- Lck sequestration as the molecular basis for selection of an MHC-restricted TCR repertoire in the thymus

- Formulation of the kinetic signaling model as the basis of CD4/CD8 and helper/effector lineage fate determination in the thymus

- identification of CD8 lineage-specifying cytokines in the thymus

- discovery of costimulatory signals as the trigger for thymic clonal deletion both in vitro and in vivo and for regulatory T cell development

- developmental diversion as the fate of thymocytes surviving negative selection

- coreceptor tuning as the mechanism of peripheral T cell homeostasis

- discovery that thymic cross-talk stimulates medullary epithelial cells to organize into a thymic medulla

- cellular basis for in vivo tissue allograft rejection

He has trained over 50 postdoctoral fellows, most of whom have become highly successful independent scientists and scientific leaders in both the United States and abroad.

Areas of Expertise

Lymphocyte Development


Selected Recent Publications

E-protein-regulated expression of CXCR4 adheres preselection thymocytes to the thymic cortex

Kadakia T, Tai X, Kruhlak M, Wisniewski J, Hwang IY, Roy S, Guinter TI, Alag A, Kehrl JH, Zhuang Y, Singer A.
J Exp Med. 216(8): 1749-61, 2019. [ Journal Article ]

A TCR mechanotransduction signaling loop induces negative selection in the thymus

Hong J, Ge C, Jothikumar P, Yuan Z, Liu B, Bai K, Li K, Rittase W, Shinzawa M, Zhang Y, Palin A, Love P, Yu X, Salaita K, Evavold BD, Singer A, Zhu C.
Nat Immunol. 19(12): 1379-90, 2018. [ Journal Article ]

Immature CD8 Single-Positive Thymocytes Are a Molecularly Distinct Subpopulation, Selectively Dependent on BRD4 for Their Differentiation

Gegonne A, Chen QR, Dey A, Etzensperger R, Tai X, Singer A, Meerzaman D, Ozato K, Singer DS.
Cell Rep. 24(1): 117-29, 2018. [ Journal Article ]

Identification of lineage-specifying cytokines that signal all CD8/cytotoxic lineage fate decisions in the thymus

Etzensperger, R, Kadakia, T, Tai, X, Alag, A., Guinter, TI, Egawa, T, Erman, B, and Singer, A.
Nat Immunol. 18: 1218-27, 2017. [ Journal Article ]

Timing and duration of MHC-I positive selection signals in the thymus are adjusted in the thymus to prevent lineage errors

Kimura, MY, Thomas, J, Tai, X, Guinter, TI, Shinzawa, M, Etzensperger, R, Li, Z, Love, P, Nakayama, T, and Singer, A.
Nat Immunol. 17: 1415-23, 2016. [ Journal Article ]

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Amala S. Alag, Ph.D.
Jennifer Ashe
Research Fellow
Sherif Badr, Ph.D.
Terry I. Guinter
Senior Associate Scientist
Xuguang Tai, Ph.D.
Postdoctoral Fellow (Visiting)
Zhongmei Zhang, Ph.D.