Defining the Transcriptomic and Epigenetic Reprogramming of Human Tumor-Infiltrating CD8 T Cells After PD-1 Blockade

Cancer Research Institute - Mark Foundation Postdoctoral Fellow (2019-2021)

Josephine Giles, PhD, University of Pennsylvania School of Medicine

Josephine Giles, PhD

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

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.

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.

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.

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.

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.

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 na├»ve and recovered individuals following mRNA vaccination. Sci Immunol. 2021.

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.

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.

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.

Giles JR, Globig AM, Kaech SM, Wherry EJ. CD8+ T cells in the cancer-immunity cycle. Immunity. 2023.

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.