Mark A. Brockman, Associate Professor
B.A., Beloit College
Phone: (778) 782-3341
Research InterestThe research in our laboratory aims to use molecular approaches to investigate key questions at the interface of virology, pathogenesis, and the human cellular immune response to human immunodeficiency virus (HIV) infection. Current studies focus on understanding the impact of viral immune escape mutations on cytotoxic T lymphocyte (CTL) recognition and on HIV protein function, measuring the ability of T cell receptors (TCR) to recognize and kill HIV-infected cells, and assessing the relevance of viral tropism and cellular compartments on disease progression. We have developed recombination strategies to generate large panels of viral variants that encode patient-derived HIV sequences. Replication capacity of these variants is being measured to define codon-specific associations in the viral Gag and Pol genes with fitness and to identify potential relationships with immune selection pressure. Similar work assesses the impact of immune escape on function of viral accessory proteins, such as Nef and Vif. The host CTL response to HIV is determined in large part by interactions between TCR and MHC class I/viral peptide complexes. We are cloning and expressing full-length TCR from virus-specific CTL in order to examine the activity of TCR variants in greater detail. Finally, changes in viral tropism and related cell death may contribute to disease progression and AIDS. We are using virion immunocapture strategies to examine viral compartmentalization in plasma in order to determine the cellular sources of HIV in infected individuals over time.
- Brockman MA , Kwon DS, Tighe DP, Pavlik DF, Rosato PC, Sela J, Porichis F, Legall S, Waring MT, Moss K, Jessen H, Pereyra F, Kavanagh DG, Walker BD, and Kaufmann DE. 2009. IL-10 is upregulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells. Blood 114:346-56.
- Chen H, Piechocka-Trocha A, Miura T, Brockman MA, Julg BD, Baker BM, Rothchild AC, Block BL, Schneidewind A, Koibuchi T, Pereyra F, Allen TM, Walker BD. 2009. Differential neutralization of HIV replication in autologous CD4 T cells by HIV-specific CTL. Journal of Virology 83:3138-49.
- Miura T, Brockman MA, Brumme ZL, Brumme CJ, Pereyra F, Trocha A, Block BL, Schneidewind A, Allen TM, Heckerman D, and Walker BD. 2009. HLA-associated alterations in replication capacity of chimeric NL4-3 viruses carrying gag-protease from elite controllers of human immunodeficiency virus type 1. Journal of Virology 83:140-9.
- Brockman MA , Schneidewind A, Lahaie M, Schmidt A, Miura T, Desouza I, Ryvkin F, Derdeyn CA, Allen S, Hunter E, Mulenga J, Goepfert PA, Walker BD, and Allen TM. 2007. Escape and compensation from early HLA-B57-mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A. Journal of Virology 81:12608-18.
- Brockman MA , Tanzi GO, Walker BD, and Allen TM. 2006. Use of a novel GFP reporter cell line to examine replication capacity of CXCR4- and CCR5-tropic HIV-1 by flow cytometry. Journal of Virological Methods 131:134-42.