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Our Science – Singer Website

Alfred Singer, M.D.

Selected Publications

1)  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: 1326-1341, 2013.
2)  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.
3)  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.
Nat. Immunol. 14: 143-51, 2013.
4)  McCaughtry TM, Etzensperger R, Alag A, Tai X, Kurtulus S, Park JH, Grinberg A, Love P, Feigenbaum L, Erman B, Singer A.
Conditional deletion of cytokine receptor chains reveals that IL-7 and IL-15 specify CD8 cytotoxic lineage fate in the thymus.
J. Exp. Med. 209: 2263-76, 2012.
5)  Van Laethem F, Tikhonova AN, Singer A.
MHC restriction is imposed on a diverse T cell receptor repertoire by CD4 and CD8 co-receptors during thymic selection.
Trends Immunol. 33: 437-41, 2012.
6)  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. 13: 569-78, 2012.
7)  Gegonne A, Tai X, Zhang J, Wu G, Zhu J, Yoshimoto A, Hanson J, Cultraro C, Chen QR, Guinter T, Yang Z, Hathcock K, Singer A, Rodriguez-Canales J, Tessarollo L, Mackem S, Meerzaman D, Buetow K, Singer DS.
The general transcription factor TAF7 is essential for embryonic development but not essential for the survival or differentiation of mature T cells.
Mol. Cell. Biol. 32: 1984-97, 2012.
8)  Tai X, Van Laethem F, Pobezinsky L, Guinter T, Sharrow SO, Adams A, Granger L, Kruhlak M, Lindsten T, Thompson CB, Feigenbaum L, Singer A.
Basis of CTLA-4 function in regulatory and conventional CD4(+) T cells.
Blood. 119: 5155-63, 2012.
9)  Adoro S, Park J, Singer A.
Coreceptor gene.
Cell Cycle. 11: 833-4, 2012.
10)  Tikhonova AN, Van Laethem F, Hanada K, Lu J, Pobezinsky LA, Hong C, Guinter TI, Jeurling SK, Bernhardt G, Park J, Yang JC, Sun PD, Singer A.
alpha-beta T cell receptors that do not undergo major histocompatibility complex-specific thymic selection possess antibody-like recognition specificities.
Immunity. 36: 79-91, 2012.
11)  Adoro S, McCaughtry T, Erman B, Alag A, Van Laethem F, Park JH, Tai X, Kimura M, Wang L, Grinberg A, Kubo M, Bosselut R, Love P, Singer A.
Coreceptor gene imprinting governs thymocyte lineage fate.
EMBO J. 31: 366-77, 2012.
12)  Landry JW, Banerjee S, Taylor B, Aplan PD, Singer A, Wu C.
Chromatin remodeling complex NURF regulates thymocyte maturation.
Genes Dev. 25: 275-86, 2011.
13)  Singer A.
Molecular and cellular basis of T cell lineage commitment: An overview.
Semin. Immunol. 22: 253, 2010.
14)  Park J, Adoro S, Singer A.
Ting G, Yang Y, eds.
Coreceptor tuning: A cytokine-mediated homestatic mechanism that maximizes CD8 T cell reactivity while maintaining peripheral tolerance. In: The life and death of T lymphocytes - The influence of cytokines under physiological and pathological conditions.
Kerala, India: Transworld Research Network Publishers; 2010. p. 1-14 [Book Chapter]
15)  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. 11: 257-64, 2010.
16)  Sarafova SD, Van Laethem F, Adoro S, Guinter T, Sharrow SO, Feigenbaum L, Singer A.
Upregulation of CD4 expression during MHC class II-specific positive selection is essential for error-free lineage choice.
Immunity. 31: 480-90, 2009.
17)  Adoro S, Erman B, Sarafova SD, Van Laethem F, Park JH, Feigenbaum L, Singer A.
Targeting CD4 coreceptor expression to postselection thymocytes reveals that CD4/CD8 lineage choice is neither error-prone nor stochastic.
J. Immunol. 181: 6975-83, 2008.
18)  Singer A, Adoro S, Park J.
Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice.
Nat. Rev. Immunol. 8: 788-801, 2008.
19)  Van Laethem F, Sarafova SD, Park JH, Tai X, Pobezinsky L, Guinter TI, Adoro S, Adams A, Sharrow SO, Feigenbaum L, Singer A.
Deletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC.
Immunity. 27: 735-50, 2007.
20)  Park JH, Adoro S, Lucas PJ, Sarafova SD, Alag AS, Doan LL, Erman B, Liu X, Ellmeier W, Bosselut R, Feigenbaum L, Singer A.
'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR.
Nat. Immunol. 8: 1049-59, 2007.
21)  Tai X, Van Laethem F, Sharpe AH, Singer A.
Induction of autoimmune disease in CTLA-4 / mice depends on a specific CD28 motif that is required for in vivo costimulation.
Proc. Natl. Acad. Sci. U.S.A. 104: 13756-61, 2007.
22)  Erman B, Alag AS, Dahle O, van Laethem F, Sarafova SD, Guinter TI, Sharrow SO, Grinberg A, Love PE, Singer A.
Coreceptor signal strength regulates positive selection but does not determine CD4/CD8 lineage choice in a physiologic in vivo model.
J. Immunol. 177: 6613-25, 2006.
23)  Graham DB, Bell MP, Huntoon CJ, Griffin MD, Tai X, Singer A, McKean DJ.
CD28 Ligation Costimulates Cell Death but Not Maturation of Double-Positive Thymocytes due to Defective ERK MAPK Signaling.
J. Immunol. 177: 6098-107, 2006.
24)  Yu Q, Park JH, Doan LL, Erman B, Feigenbaum L, Singer A.
Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection.
J. Exp. Med. 203: 165-75, 2006.
25)  Sarafova SD, Erman B, Yu Q, Van Laethem F, Guinter T, Sharrow SO, Feigenbaum L, Wildt KF, Ellmeier W, Singer A.
Modulation of coreceptor transcription during positive selection dictates lineage fate independently of TCR/coreceptor specificity.
Immunity. 23: 75-87, 2005.
26)  Tai X, Cowan M, Feigenbaum L, Singer A.
CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2.
Nat Immunol. 6: 152-62, 2005.
27)  Yu Q, Erman B, Park JH, Feigenbaum L, Singer A.
IL-7 receptor signals inhibit expression of transcription factors TCF-1, LEF-1, and RORgammat: impact on thymocyte development.
J Exp Med. 200: 797-803, 2004.
28)  Park JH, Yu Q, Erman B, Appelbaum JS, Montoya-Durango D, Grimes HL, Singer A.
Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival.
Immunity. 21: 289-302, 2004.
29)  Erman B, Guinter TI, Singer A.
Defined alphabeta T cell receptors with distinct ligand specificities do not require those ligands to signal double negative thymocyte differentiation.
J Exp Med. 199: 1719-24, 2004.
30)  Singer A, Bosselut R.
CD4/CD8 coreceptors in thymocyte development, selection, and lineage commitment: analysis of the CD4/CD8 lineage decision.
Adv Immunol. 83: 91-131, 2004.
31)  Bosselut R, Guinter TI, Sharrow SO, Singer A.
Unraveling a Revealing Paradox: Why Major Histocompatibility Complex I-signaled Thymocytes.
J Exp Med. 197: 1709-19, 2003.
32)  Bhandoola A, Rosenberg AS, Singer A.
CD4(+) T-cell responses to self-peptide-MHC.
Trends Immunol. 24: 171, 2003.
33)  Doan LL, Kitay MK, Yu Q, Singer A, Herblot S, Hoang T, Bear SE, Morse HC, Tsichlis PN, Grimes HL.
Growth factor independence-1B expression leads to defects in T cell activation, IL-7 receptor alpha expression, and T cell lineage commitment.
J Immunol. 170: 2356-66, 2003.
34)  Yu Q, Erman B, Bhandoola A, Sharrow SO, Singer A.
In vitro evidence that cytokine receptor signals are required for differentiation of double positive thymocytes into functionally mature CD8+ T cells.
J Exp Med. 197: 475-87, 2003.
35)  Bhandoola A, Tai X, Eckhaus M, Auchincloss H, Mason K, Rubin SA, Carbone KM, Grossman Z, Rosenberg AS, Singer A.
Peripheral expression of self-MHC-II influences the reactivity and self-tolerance of mature CD4(+) T cells: evidence from a lymphopenic T cell model.
Immunity. 17: 425-36, 2002.
36)  Bhandoola A, Bosselut R, Yu Q, Cowan ML, Feigenbaum L, Love PE, Singer A.
CD5-mediated inhibition of TCR signaling during intrathymic selection and development does not require the CD5 extracellular domain.
Eur J Immunol. 32: 1811-7, 2002.
37)  Erman B, Feigenbaum L, Coligan JE, Singer A.
Early TCRalpha expression generates TCRalphagamma complexes that signal the DN-to-DP transition and impair development.
Nat Immunol. 3: 564-9, 2002.
38)  Singer A.
New perspectives on a developmental dilemma: the kinetic signaling model and the importance of signal duration for the CD4/CD8 lineage decision.
Curr Opin Immunol. 14: 207-15, 2002.
39)  Bosselut R, Feigenbaum L, Sharrow SO, Singer A.
Strength of signaling by CD4 and CD8 coreceptor tails determines the number but not the lineage direction of positively selected thymocytes.
Immunity. 14: 483-94, 2001.
40)  McKean DJ, Huntoon CJ, Bell MP, Tai X, Sharrow S, Hedin KE, Conley A, Singer A.
Maturation versus death of developing double-positive thymocytes reflects competing effects on Bcl-2 expression and can be regulated by the intensity of CD28 costimulation.
J. Immunol. 166: 3468-75, 2001.
41)  Bhandoola A, Dolnick B, Fayad N, Nussenzweig A, Singer A.
Immature thymocytes undergoing receptor rearrangements are resistant to an Atm-dependent death pathway activated in mature T cells by double-stranded DNA breaks.
J. Exp. Med. 192: 891-7, 2000.
42)  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. 13: 59-71, 2000.
43)  Bhandoola A, Kithiganahalli B, Granger L, Singer A.
Programming for cytotoxic effector function occurs concomitantly with CD4 extinction during CD8(+) T cell differentiation in the thymus.
Int Immunol. 12: 1035-40, 2000.
44)  Cibotti R, Bhandoola A, Guinter TI, Sharrow SO, Singer A.
CD8 coreceptor extinction in signaled CD4(+)CD8(+) thymocytes: coordinate roles for both transcriptional and posttranscriptional regulatory mechanisms in developing thymocytes.
Mol Cell Biol. 20: 3852-9, 2000.
45)  Bosselut R, Kubo S, Guinter T, Kopacz JL, Altman JD, Feigenbaum L, Singer A.
Role of CD8beta domains in CD8 coreceptor function: importance for MHC I binding, signaling, and positive selection of CD8+ T cells in the thymus.
Immunity. 12: 409-18, 2000.
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This page was last updated on 9/13/2013.