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

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 naïve and recovered individuals following mRNA vaccination. Sci Immunol. 2021.

BACK TO OUR PORTFOLIO