Dr. David Brooks’ laboratory is focused on understanding the mechanisms of viral pathogenesis and immunity that lead to effective virus clearance versus viral persistence. In particular, they are interested in the interplay between the myriad of signals and factors that program T-cell immunity and how they culminate in distinct functional outcomes.
Current projects in the laboratory include identifying the regulatory factors that program productive versus abortive T-cell responses, defining the factors that sustain T-cell immunity during periods of viral persistence and imaging immune cells and the immunosuppressive interactions that lead to viral persistence in vivo. Brooks’ laboratory is additionally interested in molecularly defining CD4 T-cell help and exploring the precise mechanisms of CD4 T-cell help that program functional memory T-cell differentiation following an acute infection and that sustain antiviral T-cell activity to control persistent viral infection. Ultimately, Brooks’ hope is that the elucidation of these mechanisms will aid in the development of novel targeted-vaccine strategies that enhance immunity, prevent infection and therapeutically correct immune dysfunction to control persistent viral infections.
Selected Cancer-Related Publications:
Elsaesser H, Sauer K, Brooks DG. IL-21 is required to control chronic viral infection. Science. 2009 Jun 19;324(5934):1569-72. Epub 2009 May 7.
Garidou L, Heydari S, Truong P, Brooks DG, McGavern DB. Therapeutic memory T cells require costimulation for effective clearance of a persistent viral infection. J Virol. 2009 Sep;83(17):8905-15. Epub 2009 Jun 24.
Brooks DG, Ha SJ, Elsaesser H, Sharpe AH, Freeman GJ, Oldstone MB. IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection. Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20428-33. Epub 2008 Dec 15.
Brooks DG, Lee AM, Elsaesser H, McGavern DB, Oldstone MB. IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection. J Exp Med. 2008 Mar 17;205(3):533-41. Epub 2008 Mar 10.
Brooks DG, Trifilo MJ, Edelmann KH, Teyton L, McGavern DB, Oldstone MB. Interleukin-10 determines viral clearance or persistence in vivo. Nat Med. 2006 Nov;12(11):1301-9. Epub 2006 Oct 15.