Thomas Griffith,  PhD

Thomas S. Griffith earned his Ph.D. from Washington University (St. Louis, MO) in 1996 examining the cellular and molecular mechanisms of ocular immune privilege. From 1997-1999, Dr. Griffith was a postdoctoral scientist at Immunex Corporation (Seattle, WA). While at Immunex, Dr. Griffith contributed to the initial characterization of TRAIL (TNF-related apoptosis-inducing ligand). Dr. Griffith moved to the Department of Urology at the University of Iowa in 1999, where he continued his evaluation of TRAIL as an antitumor therapeutic. Since August 2011, Dr. Griffith has been an Associate Professor in the Department of Urology at the University of Minnesota. Dr. Griffith is also a member of the Masonic Cancer Center, the Center for Immunology, and the Microbiology, Immunology, and Cancer Biology Graduate Program at the University of Minnesota.

Tumor immunology, apoptosis
The research in my laboratory studies the therapeutic potential of apoptotic cell death in the treatment of cancer. The tumor necrosis family member, TRAIL/Apo-2 ligand, is a potent inducer of tumor cell apoptosis, but is non-toxic against normal cell and tissues, suggesting that TRAIL might be administered as an antitumor therapeutic without the side effects seen with other TNF family members, namely TNF and Fas ligand, and traditional chemotherapeutics.

Employment of various gene delivery systems, such as non-replicative viral vectors, is making it possible to administer genes directly into tumors sites in situ. Using this technology, a recombinant, replication-deficient adenoviral vector encoding the full-length TRAIL cDNA (Ad-TRAIL) was developed in the laboratory as a way to induce tumor cell death. Current experiments are investigating the ability of Ad-TRAIL to activate systemic antitumor immunity.

Additional studies are investigating the ability of apoptotic cells to influence the immune response. For these studies, we use a number of experimental model of tolerance as well as an experimental model of sepsis.

• Hamilton SE, Griffith TS. A wild microbiome improves mouse modeling of the human immune response.Lab Anim (NY). 2019 Nov.
• Huggins MA, Sjaastad FV, Pierson M, Kucaba TA, Swanson W, Staley C, Weingarden AR, Jensen IJ, Danahy DB, Badovinac VP, Jameson SC, Vezys V, Masopust D, Khoruts A, Griffith TS, Hamilton SE. Microbial Exposure Enhances Immunity to Pathogens Recognized by TLR2 but Increases Susceptibility to Cytokine Storm through TLR4 Sensitization. Cell Rep. 2019 Aug 13
• Danahy DB, Kurup SP, Winborn CS, Jensen IJ, Harty JT, Griffith TS, Badovinac VP. Sepsis-Induced State of Immunoparalysis Is Defined by Diminished CD8 T Cell-Mediated Antitumor Immunity. J Immunol. 2019 Aug 
• Picarda G, Ghosh R, McDonald B, Verma S, Thiault N, El Morabiti R, Griffith TS, Benedict CA. Cytomegalovirus Evades TRAIL-Mediated Innate Lymphoid Cell 1 Defenses. J Virol. 2019 Jul 30.
• Danahy DB, Jensen IJ, Griffith TS, Badovinac VP. Cutting Edge: Polymicrobial Sepsis Has the Capacity to Reinvigorate Tumor-Infiltrating CD8 T Cells and Prolong Host Survival. J Immunol. 2019 May 15
• Kim H, Khanna V, Kucaba TA, Zhang W, Ferguson DM, Griffith TS, Panyam J. Combination of Sunitinib and PD-L1 Blockade Enhances Anticancer Efficacy of TLR7/8 Agonist-Based Nanovaccine. Mol Pharm. 2019 Mar 4.
• Kim H, Griffith TS, Panyam J. Poly(d,l-lactide-co-glycolide) Nanoparticles as Delivery Platforms for TLR7/8 Agonist-Based Cancer Vaccine. J Pharmacol Exp Ther. 2019 Sep.
• Sjaastad FV, Condotta SA, Kotov JA, Pape KA, Dail C, Danahy DB, Kucaba TA, Tygrett LT, Murphy KA, Cabrera-Perez J, Waldschmidt TJ, Badovinac VP, Griffith TS. Polymicrobial Sepsis Chronic Immunoparalysis Is Defined by Diminished Ag-Specific T Cell-Dependent B Cell Responses. Front Immunol. 2018 Oct 31
  
• EL Brincks, P Gurung, RA Langlois, EA Hemann, KL Legge, TS Griffith. 2011. The magnitude of the T cell response to a clinically-significant dose of influenza virus is regulated by TRAIL. Journal of Immunology. In press.