David Brooks, PhD

Our laboratory is focused on understanding the mechanisms of viral pathogenesis and immunity that lead to effective virus clearance versus viral persistence. In particular, we are interested in the interplay between the myriad of signals and factors that program innate immunity and T cell responses to culminate in distinct functional outcomes. In order to understand the mechanisms that lead to divergent T cell responses, our laboratory uses the lymphocytic choriomeningitis virus (LCMV) model of murine infection. LCMV is an excellent model for exploratory studies in virus:host interactions and has served as a prototype for dissecting the success or failure of immune responses in acute and persistent infections. We have implemented this system to establish that host-mediated immunosuppressive mechanisms and chronic inflammatory signals are dually invoked by infection with persisting viruses leading to the loss of T cell function and the inability to clear infection. We have shown that therapeutic blockade of these immunosuppressive and inflammatory factors restores T cell activity eliminating persistent infection, suggesting a viable approach to enable long-term immune mediated control of persistent virus infections.

Many of the same inflammatory and immunosuppressive mechanisms that regulate antiviral immunity during persistent infection are also utilized to inhibit the immune response against cancer. Through our studies of immunity to persistent virus infection, our laboratory has begun to explore the mechanisms that limit anti-tumour responses and how to enhance the immune response to eliminate cancer. We believe that by comparing two disease states characterized by chronic inflammation and immunosuppression (i.e., persistent virus infection and cancer) that the conserved and most important mechanisms of immune inhibition can be identified, leading to the development of vaccine strategies and immunotherapies that will be effective against a broad range of chronic diseases.

Among the interests in the laboratory are to explore: (1) the mechanisms of immunosuppression that drive innate cell dysfunction and T cell exhaustion in persistent virus infection and cancer and how to reverse them to cure disease; (2) how chronic inflammation and type I interferon signaling alter immunity to persistent viruses and cancer; and (3) the mechanisms of B cell and antibody mediated immunity following vaccination, and acute and persistent virus infections. Overall, our goal is to use this information to develop novel and comprehensive immunotherapeutic strategies to fight persistent virus infections and cancer.
Front Oncol. 2019;9:415
Gadalla R, Noamani B, MacLeod BL, Dickson RJ, Guo M, Xu W, Lukhele S, Elsaesser HJ, Razak ARA, Hirano N, McGaha TL, Wang B, Butler M, Guidos CJ, Ohashi PS, Siu LL, Brooks DG
Semin Immunol. 2019 May 30;:101277
Lukhele S, Boukhaled GM, Brooks DG
J Immunol. 2019 Jul 01;203(1):293
Woo JS, Srikanth S, Kim KD, Elsaesser H, Lu J, Pellegrini M, Brooks DG, Sun Z, Gwack Y
JCI Insight. 2019 May 14;5:
Palchevskiy V, Xue YY, Kern R, Weigt SS, Gregson AL, Song SX, Fishbein MC, Hogaboam CM, Sayah DM, Lynch Iii JP, Keane MP, Brooks DG, Belperio JA
Cell. 2019 Apr 04;177(2):492-493
Rojas OL, Pröbstel AK, Porfilio EA, Wang AA, Charabati M, Sun T, Lee DSW, Galicia G, Ramaglia V, Ward LA, Leung LYT, Najafi G, Khaleghi K, Garcillán B, Li A, Besla R, Naouar I, Cao EY, Chiaranunt P, Burrows K, Robinson HG, Allanach JR, Yam J, Luck H,...
J Immunother Cancer. 2019 Mar 13;7(1):72
Clouthier DL, Lien SC, Yang SYC, Nguyen LT, Manem VSK, Gray D, Ryczko M, Razak ARA, Lewin J, Lheureux S, Colombo I, Bedard PL, Cescon D, Spreafico A, Butler MO, Hansen AR, Jang RW, Ghai S, Weinreb I, Sotov V, Gadalla R, Noamani B, Guo M, Elston S,...
Cell. 2018 Dec 21;:
Rojas OL, Pröbstel AK, Porfilio EA, Wang AA, Charabati M, Sun T, Lee DSW, Galicia G, Ramaglia V, Ward LA, Leung LYT, Najafi G, Khaleghi K, Garcillán B, Li A, Besla R, Naouar I, Cao EY, Chiaranunt P, Burrows K, Robinson HG, Allanach JR, Yam J, Luck H,...
Immunity. 2018 Oct 16;49(4):678-694.e5
Snell LM, MacLeod BL, Law JC, Osokine I, Elsaesser HJ, Hezaveh K, Dickson RJ, Gavin MA, Guidos CJ, McGaha TL, Brooks DG
J Immunol. 2018 Jul 09;:
Woo JS, Srikanth S, Kim KD, Elsaesser H, Lu J, Pellegrini M, Brooks DG, Sun Z, Gwack Y
Clin Microbiol Infect. 2018 Jun 12;:
Harding-Esch EM, Fuller SS, Christine Chow SL, Nori AV, Harrison MA, Parker M, Piepenburg O, Forrest MS, Brooks DG, Patel R, Hay P, Fearnley N, Pond MJ, Kevin Dunbar J, Butcher PD, Planche T, Lowndes CM, Tariq Sadiq S

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Associate Professor, Department of Immunology, University of Toronto