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Directory >> Philip D. Greenberg, MD

Faculty

Contact Information

Philip D. Greenberg, MD

  • Professor, Division of Oncology, Department of Medicine and Department of Immunology
  • University of Washington
  • Member, Clinical Research Division
    Fred Hutchinson Cancer Research Center

The Philip Greenberg laboratory is focused on developing cellular and molecular strategies to modulate T cell function for the purpose of treating viral and malignant diseases. Studies in the lab in murine models developed the principles and technologies for performing adoptive T cell therapy, in which rare antigen-specific T cells present in the host are isolated, cloned, and expanded to large numbers in vitro, and re-infused into the host to establish a potent immune response. More recently, the laboratory has been pursuing strategies to genetically engineer T cells using retroviral-mediated gene transfer to acquire additional functions that may enhance therapeutic efficacy and antiviral activity. In particular, we have developed methods to disrupt regulatory pathways operative intracellularly in CD8+ T cells that limit the efficacy of these T cells in the context of targeting high antigen burdens or the tumor microenvironment.

The lab is also pursuing a basic/preclinical development project using transgenic and knocking mice to understand the mechanisms by which high, persistent antigen burdens, such as self-antigens, chronic viral infections, or progressive tumors reprogram the epigenetic and transcriptional status of T cells to render then anergic or functionally exhausted. Other training grant faculty with whom members of this laboratory interact and/or collaborate include Drs. Larry Corey, Julie McElrath, and Denise Galloway.


Selected Publications


Blattman JN, Greenberg PD. PD-1 blockade: rescue from a near-death experience. Nat Immunol. 2006; 7(3): 227-8.
PubMed Abstract


Kraft AR, Krux F, Schimmer S, Ohlen C, Greenberg PD, Dittmer U. CpG oligodeoxynucleotides allow for effective adoptive T-cell therapy in chronic retroviral infection. Blood. 2007; 109(7): 2982-4.
PubMed Abstract


Teague RM, Greenberg PD, Fowler C, et al. Peripheral CD8+ T cell tolerance to self-proteins is regulated proximally at the T cell receptor. Immunity. 2008; 28(5): 662-74.
PubMed Abstract


Wölfl M, Rutebemberwa A, Mosbruger T, Mao Q, Li HM, Netski D, Ray SC, Pardoll D, Sidney J, Sette A, Allen T, Kuntzen T, Kavanagh DG, Kuball J, Greenberg PD, Cox AL. Hepatitis C virus immune escape via exploitation of a hole in the T cell repertoire. J Immunol. 2008; 181(9): 6435-46.
PubMed Abstract


Kuball J, Hauptrock B, Malina V, Antunes E, Voss RH, Wolfl M, Strong R, Theobald M, Greenberg PD. Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain. J Exp Med. 2009; 206(2): 463-75.
PubMed Abstract

Schietinger A, Delrow JJ, Basom RS, Blattman JN, Greenberg PD. Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state. Science. 2012 Feb 10;335(6069):723-7.
PubMed Abstract

Schietinger A, Greenberg PD. Tolerance and exhaustion: defining mechanisms of T cell dysfunction. Trends Immunol. 2014 Feb;35(2):51-60.

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