David Brooks

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.
J Clin Invest. 2017 Jan 03;127(1):260-268
Zhen A, Rezek V, Youn C, Lam B, Chang N, Rick J, Carrillo M, Martin H, Kasparian S, Syed P, Rice N, Brooks DG, Kitchen SG
Cell Rep. 2016 Sep 20;16(12):3286-96
Snell LM, Osokine I, Yamada DH, De la Fuente JR, Elsaesser HJ, Brooks DG
PLoS Pathog. 2016 Jan;12(1):e1005356
Cunningham CR, Champhekar A, Tullius MV, Dillon BJ, Zhen A, de la Fuente JR, Herskovitz J, Elsaesser H, Snell LM, Wilson EB, de la Torre JC, Kitchen SG, Horwitz MA, Bensinger SJ, Smale ST, Brooks DG
Cell. 2015 Dec 17;163(7):1716-29
York AG, Williams KJ, Argus JP, Zhou QD, Brar G, Vergnes L, Gray EE, Zhen A, Wu NC, Yamada DH, Cunningham CR, Tarling EJ, Wilks MQ, Casero D, Gray DH, Yu AK, Wang ES, Brooks DG, Sun R, Kitchen SG, Wu TT, Reue K, Stetson DB, Bensinger SJ
EMBO Rep. 2015 Jun;16(6):753-68
Walsh NC, Waters LR, Fowler JA, Lin M, Cunningham CR, Brooks DG, Rehg JE, Morse HC, Teitell MA
Immunity. 2015 Feb 17;42(2):379-90
Yamada DH, Elsaesser H, Lux A, Timmerman JM, Morrison SL, de la Torre JC, Nimmerjahn F, Brooks DG
PLoS One. 2014;9(8):e103091
Boyle DS, McNerney R, Teng Low H, Leader BT, Pérez-Osorio AC, Meyer JC, O'Sullivan DM, Brooks DG, Piepenburg O, Forrest MS
Trends Microbiol. 2013 Dec;21(12):634-40
Wilson EB, Brooks DG
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):E4904-12
Gillespie EJ, Ho CL, Balaji K, Clemens DL, Deng G, Wang YE, Elsaesser HJ, Tamilselvam B, Gargi A, Dixon SD, France B, Chamberlain BT, Blanke SR, Cheng G, de la Torre JC, Brooks DG, Jung ME, Colicelli J, Damoiseaux R, Bradley KA

Pages


Associate Professor, Department of Immunology, University of Toronto