Greg M Delgoffe, PhD
- Postdoc, St. Jude Children's Research Hospital
- PhD, Johns Hopkins University
- BS, Western Michigan University
Assistant Professor, Department of Immunology
Member, University of Pittsburgh Cancer Institute
Chair, Graduate Program in Microbiology and Immunology (PMI) Admissions Committee
Member, Graduate Program in Microbiology and Immunology (PMI)
The Delgoffe Lab studies the impact of the tumor microenvironment on T cell subsets that infiltrate the tumor. We aim to dissect how tumor cells promote an immunosuppressive environment through the modulation of metabolism. We are currently examining this from two major perspectives.
- Immunometabolism of tumor-infiltrating Treg cells
Treg cells, while critical for preventing autoimmunity, provide a major barrier to antitumor immunity. Our studies suggest that tumors promote the function of these suppressive T cells by providing critical metabolic intermediates that support Treg cell function. We aim to dissect how different metabolites promote or inhibit Treg cell function generally, as well as determine whether these pathways can be targeted to relieve tumor-induced suppression and promote antitumor immunity.
- Metabolic reprogramming of exhausted antitumor CTLs
Tumors provide chronic TCR stimulation to tumor-specific cytotoxic lymphocytes, as well as stimulation through co-inhibitory receptors. This results in a dysfunctional T cell phenotype known as T cell exhaustion. We hypothesize that T cell exhaustion is a metabolic phenotype, and that metabolism can be reprogrammed in tumor-specific CTLs to enhance their function, resulting in heightened antitumor responses.
Dr. Delgoffe is currently accepting graduate students for rotations in the laboratory, as well as applications for postdoctoral fellows.
Cancer Immunology Journal Club - University of Pittsburgh Cancer Institute
Dr. Delgoffe runs a journal club that meets on the most Wednesdays of every month at 5:00pm in the Second Floor Conference Room at the Hillman Cancer Center. We discuss any interesting, cool, or novel papers in the broad field of immunology and inflammation related to cancer. If you are interested in attending or presenting at the journal club, please email Dr. Delgoffe (firstname.lastname@example.org) to be added to our weekly mailing list.
Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE, Watkins SC, Ferris RL, Delgoffe GM. “The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction.” Immunity. 2016 Aug 16;45(2):374-88.
Scharping NE*, Menk AV*, Whetstone RD, Zeng X, Delgoffe GM. "Efficacy of PD-1 blockade is potentiated by metformin-induced reduction of tumor hypoxia." Cancer Immunol Res. 2016 Dec 9.
Bengsch B, Johnson AL, Kurachi M, Odorizzi PM, Pauken KE, Attanasio J, Stelekati E, McLane LM, Paley MA, Delgoffe GM, Wherry EJ. “Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the Inhibitory Receptor PD-1 Are an Early Driver of CD8(+) T Cell Exhaustion.” Immunity. 2016 Aug 16;45(2):358-73.
Pollizzi KN, Sun IH, Patel CH, Lo YC, Oh MH, Waickman AT, Tam AJ, Blosser RL, Wen J, Delgoffe GM, Powell JD. “Asymmetric inheritance of mTORC1 kinase activity during division dictates CD8(+) T cell differentiation.” Nat Immunol. 2016 Jun;17(6):704-11.
Turnis ME, Sawant DV, Szymczak-Workman AL, Andrews LP, Delgoffe GM, Yano H, Beres AJ, Vogel P, Workman CJ, Vignali DA. “Interleukin-35 Limits Anti-Tumor Immunity.” Immunity. 2016 Feb 16;44(2):316-29.Delgoffe GM, Powell JD. “Feeding an army: The metabolism of T cells in activation, anergy, and exhaustion.” Mol Immunol. 2015 Dec;68(2 Pt C):492-
Pollizzi KN, Patel CH, Sun IH, Oh MH, Waickman AT, Wen J, Delgoffe GM, and Powell JD. "mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation." J Clin Invest. 2015 125(5):2090-108.
Delgoffe GM*, Woo SR*, Turnis ME, Guy CS, Gravano DM, Bettini ML, Finkelstein DF, Vogel P, Workman CJ and Vignali DA. “Stability and function of regulatory T cells is maintained by a neuropilin-1–semaphorin-4a axis.” Nature. 501 (7466) , pp. 252-256. 2013 Sep 12. doi:10.1038/nature12428
Collison LW*, Delgoffe GM*, Guy CS, Vignali KM, Chaturvedi V, Fairweather D, Satoskar AR, Garcia KC, Hunter CA, Drake CG, Murray PJ, Vignali DA. “The composition and signaling of the IL-35 receptor are unconventional.” Nat Immunol. 2012 Feb 5. doi: 10.1038/ni.2227.
Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ, Horton MR, Xiao B, Worley PF, and Powell JD. “The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2.” Nat Immunol. 2011 Feb 27.
Zheng Y*, Delgoffe GM*, Meyer CF*, Chan W, Powell JD. "Anergic T cells are metabolically anergic." J Immunol. 2009 Oct 19.
Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthew KL, Xiao B, Worley PF, Kozma SC, Powell JD. “The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment.” Immunity. 2009 Jun 19; 30(6):832-44.