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Benjamin A. Youngblood, PhD
Benjamin A. Youngblood, PhD

Benjamin A. Youngblood, PhD

Member, St. Jude Faculty

Departments

Education

RT-Assistant Professor – Emory University School of Medicine, Atlanta, GA
Postdoctoral Fellow – Emory University School of Medicine, Atlanta, GA
PhD – University of California Santa Barbara, Santa Barbara, CA
BS – Oregon State University, Corvallis, OR

Research Interests

  • Viral Immunity
  • CD8 T cell memory differentiation
  • CD8 T cell exhaustion
  • Epigenetic regulation of T cell functions
  • Therapeutic vaccination 

Selected Publications

Lan X, Mi T, Alli S, Guy C, Djekidel MN, Liu X, Boi S, Chowdhury P, He M, Zehn D, Feng Y, Youngblood B*. Antitumor progenitor exhausted CD8 T cells are sustained with TCR engagement. Nature Immunology, June 25, pages 1046–1058 (2024)

Mi T, Soerens AG, Alli S, Kang T, Vasandan A, Wang Z, Vezys V, Kimura S, Iacobucci I, Baylin SB, Jones PA, Hiner C, Mueller A, Goldstein H, Mullighan CG, Zebley CC, Masopust D, and Youngblood B*. Conserved epigenetic hallmarks of T-cell aging during immunity and malignancy. Nature Aging, online June 12 2024

Lan X, Zebley CC, Youngblood B.* Cellular and molecular waypoints along the of T cell exhaustion. Science Immunology Sep;8(87) 2023

Moustaki A, Crawford JC, Alli S, Fan Y, Boi S, Zamora AE, McDonald NMN, Wu G, Nakitandwe J, Newman S, Foy S, Silkov A, Thomas PG, Pappo A, Dyer MA, Stewart E, Federico S, Youngblood B*. Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation. Science Immunology. 2022 Feb. 4; 7 (68).

Zebley CC and Youngblood B * Perspective: Improving antitumor T cells. Science. 2022 Nov 11;378(6620):598

Zebley CC, Brown C, Mi T, Fan Y, Alli S, Boi S, Galletti G, Lugli E, Langfitt D, Metais J-Y, Lockey T, Meagher M, Triplett B, Talleur AC, Gottschalk S, Youngblood B. CD19-CAR T cells undergo exhaustion DNA methylation programming in patients with acute lymphoblastic leukemia. Cell Rep Nov 30;37(9):110079, 2021. doi: 10.1016/j.celrep.2021.110079. PMID: 34852226

Prinzing B, Zebley CC, Petersen CT, Fan Y, Anido AA, Yi Z, Nguyen P, Houke H, Bell M, Haydar D, Brown C, Boi SK, Alli S, Crawford JC, Riberdy JM, Park JJ, Zhou S, Velasquez MP, DeRenzo C, Lazzarotto CR, Tsai SQ, Vogel P, Pruett-Miller SM, Langfitt DM, Gottschalk S, Youngblood B, Krenciute G. Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity. Sci Transl Med Nov 17;13(620):eabh0272, 2021. doi: 10.1126/scitranslmed.abh0272. Epub 2021 Nov 17. PMID: 34788079

Zebley CC, Abdelsamed HA, Ghoneim HE, Alli S, Brown C, Haydar D, Mi T, Harris T, McGargill MA, Krenciute G, Youngblood B. Proinflammatory cytokines promote TET2-mediated DNA demethylation during CD8 T cell effector differentiation. Cell Rep Oct 12;37(2):109796, 2021. doi: 10.1016/j.celrep.2021.109796. PMID: 34644568

Zebley CC, Gottschalk S, Youngblood B. Rewriting history: Epigenetic reprogramming of CD8 T cell differentiation to enhance immunotherapy. Trends in Immunology Online July 2020.

Weinmann AS, Youngblood BA, Smale ST, Brink R, Schatz DG, Mcheyzer-Williams M. A future outlook on molecular mechanisms of immunity. Trends in Immunology Vol 41. Issue 7P549-555, July 01, 2020.

Abdelsamed HA, Zebley CC, Nguyen H, Rutishauser RL, Fan Y, Ghoneim HE, Crawford JC, Alfei F, Alli S, Ribeiro SP, Castellaw A, McGargill M, Jin H, Boi SK, Speake C, Serti E, Turka LA, Busch ME, Stone M,  Deeks SG, Sekaly RP, Zehn D, James EA, Nepom GT, Youngblood B*. Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes. Nature Immunology (5):578-587 May 2020.

Fonseca R, Beura LK, Quarnstrom CF, Ghoneim HE, Fan Y, Zebley CC, Scott MC, Fares-Frederickson NJ, Wijeyesinghe S, Thompson EA, Borges da Silva H, Vezys V, Youngblood B, Masopust D. Developmental plasticity allow outside-in immune response by resident memory T cells. Nature Immunology 4):412-421 April 2020.

Lugli E, Galletti G, Boi SK, Youngblood BA. Stem, effector, and hybrid states of memory CD8 T cells. Trends in Immunology Vol. 41 Issue 1 P17-28, January 01, 2020.

Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, Lynn RC, Philip M, Rao A, Restifo NP, Schietinger A, Schumacher TN, Schwartzberg PL, Sharpe AH, Speiser DE, Wherry EJ, Youngblood BA, Zehn D. Defining ‘T cell exhaustion’. Nat Rev Immunol Nov;19(11):665-674, 2019.

Alfei F, Kanev K., Hofmann M, Wu M, Ghoneim HE, Roelli P, Utzschneider DT, von Hösslin M, Cullen J, Fan Y, Eisenberg V, Wohlleber D, Steiger K, Merkler D, Delorenzi M, Knolle PA, Cohen CJ, Thimme R*, Youngblood B*, and Zehn D*. Tox reinforces the phenotype and longevity of exhausted T-cells in chronic viral infection. Nature July 571(7764):265-269, 2019.

Zamora AE, Crawford JC, Allen EK, Guo XJ, Bakke J, Carter RA, Abdelsamed HA, Moustaki A, Li Y, Chang TC, Awad W, Dallas MH, Mullighan CG, Downing JR, Geiger TL, Chen T, Green DR, Youngblood B, Zhang J, and Thomas PG. Pediatric patients with acute lymphoblastic leukemia generate abundant and functional neoantigen-specific CD8+ T cell responses. Sci Transl Med Vol. 11, Issue 498, 26 Jun 2019.

Mamcarz E, Zhou S, Lockey T, Abdelsamed H, Cross SJ, Kang G, Ma Z, Condori J, Dowdy J, Triplett B, Li C, Maron G, Aldave Becerra JC, Church JA, Dokmeci E, Love JT, da Matta Ain AC, van der Watt H, Tang X, Janssen W, Ryu BY, De Ravin SS, Weiss MJ, Youngblood B, Long‑Boyle JR, Gottschalk S, Meagher MM, Malech HL, Puck JM, Cowan MJ, and Sorrentino BP. Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1. N Engl J Med Apr 18;380(16):1525-1534, 2019.

Zheng W, O'Hear C, Alli R, Basham J, Abdelsamed H, Palmer L, Jones L, Youngblood B, Geiger T. PI3K orchestration of the in vivo persistence of chimeric antigen receptor-modified T cells. Leukemia Feb 2 2018.

Youngblood B, Hale JS, Kissick, HT, Ahn, E, Xu X, Wieland A, Araki K, West EE, Ghoneim HE, Fan Y, Dogra P, Davis CW, Konieczny BT, Anita R, Cheng X, Ahmed R; Effector CD8 T cells dedifferentiate into long-lived memory cells. Nature Dec 21;(552), 2017.

Akondy RS, Fitch M, Y Edupuganti S, Yang S, Edupuganti S, Kissick HT, Li K, Youngblood B, Abdelsamed H, Cohen KW, Alexe G, Nagar S, McCausland MM, Gupta S, Tata P, Haining WN, McElrath J, Zhang D, Hu B, Greenleaf WJ, Goronzy JJ, Mulligan MJ, Hellerstein M, Ahmed R; Origin and differentiation of human memory CD8 T cells after vaccination. Nature Dec 21;(552), 2017.

Allen EK, Randolph AG, Bhangale T, Dogra P, Ohlson M, Oshansky CM, Zamora AE, Shannon JP, Finkelstein D, Dressen A, DeVincenzo J, Caniza M, Youngblood B, Rosenberger CM, Thomas PG; SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans. Nature Medicine July 17;(23):975-983, 2017.

Ghoneim HE, Fan Y, Moustaki A, Abdelsamed HA, Dash P, Dogra P, Carter R, Awad W, Neale G, Thomas PG, Youngblood B, De novo epigenetic programs inhibit PD-1 blockade mediated T cell rejuvenation Cell Jun 29;170(1):142-157, 2017.

Abdelsamed HA, Moustaki A, Fan Y, Dogra P, Ghoneim HE, Zebley C, Triplett BM, Sekaly R, Youngblood B. Human memory CD8 T-cell effector-potential is epigenetically preserved during in vivo homeostasis. J Exp Med Jun 5;214(6):1593-1606, 2017.

Ghoneim HE, Zamora AE, Thomas PG, Youngblood B. Cell-Intrinsic Barriers of T Cell-Based Immunotherapy. Trends In Molecular Medicine Dec;22(12):1000-1011, 2016.

Zeng H, Cohen S, Guy C, Shrestha S, Neale G, Brown S, Cloer C, Kishton R, Gao X, Youngblood B, Do M, Li M, Locasale J, Rathmell J, Chi H. Critical roles of mTORC1 and mTORC2 kinase signaling and glucose metabolism in follicular helper T cell differentiation. Immunity Sep 20;45(3):540-54, 2016.

Ahn E, Youngblood B, Lee J, Lee J, Sarkar S, Ahmed R, Demethylation of the PD-1 Promoter Is Imprinted during the Effector Phase of CD8 T Cell Exhaustion. J Virol 90(19):8934-46, 2016.

Dogra P, Ghoneim HE, Abdelsamed HA, Youngblood B. Generating long-lived CD8(+) T-cell memory: Insights from epigenetic programs. European journal of immunology 46:1548-1562 2016. EpubJul (10.1002/eji.201545550).

Hwang S, Cobb D, Bhadra R, Youngblood B, Khan I. Increased Blimp-1 expression on exhausted CD4 T cells is responsible for CD8 T cell dysfunction during chronic Toxoplama gondii infection. J Exp Med Aug 1, 2016.

Youngblood B, Hale JS, Ahmed R. Memory CD8 T cell transcriptional plasticity. F1000Prime Reports Apr 9;7:(38), 2015.

Nakayama-Hosoya K, Ishida T, Youngblood B, Nakamura H, Hosoya N, Koga M, Koibuchi T, Iwamoto A, Kawana-Tachikawa A. Epigenetic repression of interleukin 2 expression in senescent CD4+ T cells during chronic HIV type 1 infection. J Infect Dis Jan 1;211(1):28-39, 2015.

Show More

Lu P, Youngblood B, Austin JW, Ahmed R, Boss JM. Blimp-1 attenuates PD-1 expression in CD8 T cells following acute infection. J Exp Med Mar 10;211(3):515-27, 2014. PMCID:PMC3949569. PMID:24590765.

Araki K, Youngblood B, Ahmed R. Programmed Cell Death 1-directed Immunotherapy for Enhancing T-Cell Function. In: Cold Spring Harb Symp Quant Biol– Book Chapter Volume LXXVIII. Mar 3, 2014.

Scharer CD, Barwick BG, Youngblood B, Ahmed R, Boss JM. Global DNA methylation remodeling accompanies CD8 T cell effector function. J Immunol 191(6):3419-29, 2013.

Youngblood B, Hale JS, Akondy R. Using epigenetics to define vaccine-induced memory T cells. Curr Opin Virol 3(3):371-6, 2013.

Youngblood B, Noto A, Porichis F, Akondy RS, Ndhlovu ZM, Austin JW, Bordi  R, Procopio FA, Miura T, Allen TM, Sidney J, Sette A, Walker BD, Ahmed R, Boss JM, Sékaly  RP, Kaufmann DK. Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells. J Immunol 191(2):540-4, 2013.

Youngblood B, Hale JS, Ahmed R. T-cell memory differentiation: Insights from transcriptional signatures and epigenetics. Immunology 139(3):277-84, 2013.

West EE, Jin HT, Penaloza-MacMaster P, Ha SJ, Tan WG, Youngblood B, Freeman G, Smith KA, Ahmed R. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. J Clin Invest 123(6):2604–2615, 2013.

Hale JS, Youngblood B, Latner DR, Rasheed AU, Ye L, Iyer SS, Akondy RS, Ahmed R. Distinct memory CD4 T cells with commitment to T follicular helper and T helper 1-cell lineages are generated after acute viral infection. Immunity 18(38):805-817, 2013.

Zinzow-Kramer WM, Long AB, Youngblood B, Rosenthal KM, Butler R, Mohammed AU, Skountzou I, Ahmed R, Evavold BD, Boss JM. CIITA promoter I CARD-deficient mice express functional MHC class II genes in myeloid and lymphoid compartments. Genes Immun 13(4):299-310, 2012.

Youngblood B, Wherry EJ, Ahmed R. Acquired transcriptional programming in functional and exhausted virus-specific CD8 T cells. Curr Opin HIV AIDS 7:50-57, 2012

West EE, Youngblood B, Tan WG, Jin HT, Araki K, Alexe G, Konieczny BT, Calpe S, Freeman GJ, Terhorst C, et al. Tight regulation of memory CD8(+) T cells limits their effectiveness during sustained high viral load. Immunity 35:285-298, 2011.

Youngblood B, Oestreich KJ, Ha SJ, Duraiswamy J, Akondy RS, West EE, Wei Z, Lu P, Austin JW, Riley JL, et al. Chronic virus infection enforces demethylation of the locus that encodes PD-1 in antigen-specific CD8+ T cells Immunity 35(3):400-12, 2011.

Youngblood B, Davis CW, Ahmed R. Making memories that last a lifetime: heritable functions of self-renewing memory CD8 T cells. Int Immunol 10:797-803, 2010.

Araki K, Youngblood B, Ahmed R. The role of mTOR in memory CD8 T-cell differentiation. Immunol Rev 235:234-243, 2010.

Youngblood B, Reich NO. The early expressed HIV-1 genes regulate DNMT1 expression. Epigenetics 3:149-156, 2008.

Youngblood B, Bonnist E, Dryden DT, Jones AC, Reich NO. Differential stabilization of reaction intermediates: specificity checkpoints for M.EcoRI revealed by transient fluorescence and fluorescence lifetime studies. Nucleic Acids Res 36:2917-2925, 2008.

Youngblood B, Shieh FK, Buller F, Bullock T, Reich NO. S-adenosyl-L-methionine-dependent methyl transfer: observable precatalytic intermediates during DNA cytosine methylation. Biochemistry 46:8766-8775, 2007.

Youngblood B, Buller F, Reich NO. Determinants of Sequence-Specific DNA Methylation: Target recognition and catalysis are coupled in M.HhaI. Biochemistry 45:15563-15572, 2006.

Shieh FK, Youngblood B, Reich NO. The role of Arg165 towards base flipping, base stabilization and catalysis in M.HhaI. J Mol Biol 362:516-527, 2006.

Youngblood B, Reich NO. Conformational transitions as determinants of specificity for the DNA methyltransferase EcoRI. J Biol Chem 281:26821-26831, 2006.

Youngblood B, Shieh FK, De Los Rios S, Perona JJ, Reich NO. Engineered extrahelical base destabilization enhances sequence discrimination of DNA methyltransferase M.HhaI. J Mol Biol 362:334-346, 2006.

Sharma V, Youngblood B, Reich N. Residues distal from the active site that alter enzyme function in M.HhaI DNA cytosine methyltransferase. J Biomol Struct Dyn 22:533-543, 2005.

Shieh FK, Youngblood B, Reich NO. The role of Arg165 towards base flipping, base stabilization and catalysis in M.HhaI. J Mol Biol 362:516-527, 2006.

Youngblood B, Reich NO. Conformational transitions as determinants of specificity for the DNA methyltransferase EcoRI. J Biol Chem 281:26821-26831, 2006.

Youngblood B, Shieh FK, De Los Rios S, Perona JJ, Reich NO. Engineered extrahelical base destabilization enhances sequence discrimination of DNA methyltransferase M.HhaI. J Mol Biol 362:334-346, 2006.

Sharma V, Youngblood B, Reich N. Residues distal from the active site that alter enzyme function in M.HhaI DNA cytosine methyltransferase. J Biomol Struct Dyn 22:533-543, 2005.

Shieh FK, Youngblood B, Reich NO. The role of Arg165 towards base flipping, base stabilization and catalysis in M.HhaI. J Mol Biol 362:516-527, 2006.

Youngblood B, Reich NO. Conformational transitions as determinants of specificity for the DNA methyltransferase EcoRI. J Biol Chem 281:26821-26831, 2006.

Youngblood B, Shieh FK, De Los Rios S, Perona JJ, Reich NO. Engineered extrahelical base destabilization enhances sequence discrimination of DNA methyltransferase M.HhaI. J Mol Biol 362:334-346, 2006.

Sharma V, Youngblood B, Reich N. Residues distal from the active site that alter enzyme function in M.HhaI DNA cytosine methyltransferase. J Biomol Struct Dyn 22:533-543, 2005.

Last update: August 2024

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