Dr. Giles is determining how blocking the signals that inhibit T-cell function causes reprogramming at the epigenetic level resulting in more effective cytotoxic function.
published research
Beltra JC, Abdel-Hakeem MS, Manne S, Zhang Z, Huang H, Kurachi M, Su L, Picton L, Ngiow SF, Muroyama Y, Casella V, Huang YJ, Giles JR, Mathew D, Belman J, Klapholz M, Decaluwe H, Huang AC, Berger SL, Garcia KC, Wherry EJ. Stat5 opposes the transcription factor Tox and rewires exhausted CD8+ T cells toward durable effector-like states during chronic antigen exposure. Immunity. 2023.
Giles JR, Globig AM, Kaech SM, Wherry EJ. CD8+ T cells in the cancer-immunity cycle. Immunity. 2023.
McClory SE, Bardhan O, Rome KS, Giles JR, Baxter AE, Xu L, Gimotty PA, Faryabi RB, Wherry EJ, Pear WS, Jordan MS. The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR+ CD8+ effector state, and its deletion improves checkpoint blockade. Cell Rep. 2023.
Baxter AE, Huang H, Giles JR, Chen Z, Wu JE, Drury S, Dalton K, Park SL, Torres L, Simone BW, Klapholz M, Ngiow SF, Freilich E, Manne S, Alcalde V, Ekshyyan V, Berger SL, Shi J, Jordan MS, Wherry EJ. The SWI/SNF chromatin remodeling complexes BAF and PBAF differentially regulate epigenetic transitions in exhausted CD8+ T cells. Immunity. 2023.
Daniel B, Yost KE, Hsiung S, Sandor K, Xia Y, Qi Y, Hiam-Galvez KJ, Black M, J Raposo C, Shi Q, Meier SL, Belk JA, Giles JR, Wherry EJ, Chang HY, Egawa T, Satpathy AT. Divergent clonal differentiation trajectories of T cell exhaustion. Nat Immunol. 2022.
Goel RR, Painter MM, Lundgreen KA, Apostolidis SA, Baxter AE, Giles JR, Mathew D, Pattekar A, Reynaldi A, Khoury DS, Gouma S, Hicks P, Dysinger S, Hicks A, Sharma H, Herring S, Korte S, Kc W, Oldridge DA, Erickson RI, Weirick ME, McAllister CM, Awofolaju M, Tanenbaum N, Dougherty J, Long S, D’Andrea K, Hamilton JT, McLaughlin M, Williams JC, Adamski S, Kuthuru O, Drapeau EM, Davenport MP, Hensley SE, Bates P, Greenplate AR, Wherry EJ. Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine. Cell. 2022.
Giles JR, Ngiow SF, Manne S, Baxter AE, Khan O, Wang P, Staupe R, Abdel-Hakeem MS, Huang H, Mathew D, Painter MM, Wu JE, Huang YJ, Goel RR, Yan PK, Karakousis GC, Xu X, Mitchell TC, Huang AC, Wherry EJ. Shared and distinct biological circuits in effector, memory and exhausted CD8+ T cells revealed by temporal single-cell transcriptomics and epigenetics. Nat Immunol. 2022.
Giles JR, Manne S, Freilich E, Oldridge DA, Baxter AE, George S, Chen Z, Huang H, Chilukuri L, Carberry M, Giles L, Weng NP, Young RM, June CH, Schuchter LM, Amaravadi RK, Xu X, Karakousis GC, Mitchell TC, Huang AC, Shi J, Wherry JE. Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers. Immunity. 2022.
Diorio C, Shraim R, Vella LA, Giles JR, Baxter AE, Oldridge DA, Canna SW, Henrickson SE, McNerney KO, Balamuth F, Burudpakdee C, Lee J, Leng T, Farrel A, Lambert MP, Sullivan KE, Wherry EJ, Teachey DT, Bassiri H, Behrens EM. Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction. Nat Commun. 2021.
Goel RR, Apostolidis SA, Painter MM, Mathew D, Pattekar A, Kuthuru O, Gouma S, Hicks P, Meng W, Rosenfeld AM, Dysinger S, Lundgreen KA, Kuri-Cervantes L, Adamski S, Hicks A, Korte S, Oldridge DA, Baxter AE, Giles JR, Weirick ME, McAllister CM, Dougherty J, Long S, D’Andrea K, Hamilton JT, Betts MR, Luning Prak ET, Bates P, Hensley SE, Greenplate AR, Wherry EJ. Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Sci Immunol. 2021.
Chen Z, Arai E, Khan O, Zhang Z, Ngiow SF, He Y, Huang H, Manne S, Cao Z, Baxter AE, Cai Z, Freilich E, Ali MA, Giles JR, Wu JE, Greenplate AR, Hakeem MA, Chen Q, Kurachi M, Nzingha K, Ekshyyan V, Mathew D, Wen Z, Speck NA, Battle A, Berger SL, Wherry EJ, Shi J. In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer. Cell. 2021.
Vella LA, Giles JR, Baxter AE, Oldridge DA, Diorio C, Kuri-Cervantes L, Alanio C, Pampena MB, Wu JE, Chen Z, Huang YJ, Anderson EM, Gouma S, McNerney KO, Chase J, Burudpakdee C, Lee JH, Apostolidis SA, Huang AC, Mathew D, Kuthuru O, Goodwin EC, Weirick ME, Bolton MJ, Arevalo CP, Ramos A, Jasen CJ, Conrey PE, Sayed S, Giannini HM, D’Andrea K; UPenn COVID Processing Unit, Meyer NJ, Behrens EM, Bassiri H, Hensley SE, Henrickson SE, Teachey DT, Betts MR, Wherry EJ. Deep immune profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19. Sci Immunol. 2021.
Johnnidis JB, Muroyama Y, Ngiow SF, Chen Z, Manne S, Cai Z, Song S, Platt JM, Schenkel JM, Abdel-Hakeem M, Beltra JC, Greenplate AR, Ali MA, Nzingha K, Giles JR, Harly C, Attanasio J, Pauken KE, Bengsch B, Paley MA, Tomov VT, Kurachi M, Vignali DAA, Sharpe AH, Reiner SL, Bhandoola A, Johnson FB, Wherry EJ. Inhibitory signaling sustains a distinct early memory CD8+ T cell precursor that is resistant to DNA damage. Sci Immunol. 2021.
Mathew D, Giles JR, Baxter AE, Oldridge DA, Greenplate AR, Wu JE, Alanio C, Kuri-Cervantes L, Pampena MB, D’Andrea K, Manne S, Chen Z, Huang YJ, Reilly JP, Weisman AR, Ittner CAG, Kuthuru O, Dougherty J, Nzingha K, Han N, Kim J, Pattekar A, Goodwin EC, Anderson EM, Weirick ME, Gouma S, Arevalo CP, Bolton MJ, Chen F, Lacey SF, Ramage H, Cherry S, Hensley SE, Apostolidis SA, Huang AC, Vella LA; UPenn COVID Processing Unit, Betts MR, Meyer NJ, Wherry EJ. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. 2020.
Chen Z, Ji Z, Ngiow SF, Manne S, Cai Z, Huang AC, Johnson J, Staupe RP, Bengsch B, Xu C, Yu S, Kurachi M, Herati RS, Vella LA, Baxter AE, Wu JE, Khan O, Beltra JC, Giles JR, Stelekati E, McLane LM, Lau CW, Yang X, Berger SL, Vahedi G, Ji H, Wherry EJ. TCF-1-Centered Transcriptional Network Drives an Effector versus Exhausted CD8 T Cell-Fate Decision. Immunity. 2019.