Papers
Koss, B., Shields, B. D., Taylor, E. M., Storey, A. J., Byrum, S. D., Gies, A. J., … Tackett, A. J. (2021). Epigenetic control of Cdkn2a.Arf protects tumor-infiltrating lymphocytes from metabolic exhaustion. Cancer Research, 80(21), 4707–4719.
This works utilizes a suite of techniques including proteomics, RNA sequencing, and ChIP-sequencing to explore the effect of EZH2 inhibition in T cells. EZH2 inhibition leads to a loss of mitochondrial respiration and increased sensitivity to glucose withdrawal. Further, we engineered tumor-specific T cells to express the EZH2Y641F gain-of-function mutant and these cells have a greater ability to control tumor growth in models of adoptive T cell therapy.
Shields BD, Koss B, Storey AJ, Taylor EM, et al. E-cadherin loss enables melanoma checkpoint blockade resistance by escape from CD103 immune responses. Cancer Research 79, 1113–1123 (2019).
We investigated the role of E-cadherin in checkpoint blockade and through genetic manipulation show that E-cadherin promotes checkpoint responsiveness in a CD103 dependent manor.
Additional Publications
Azevedo-Pouly A. C., Appell L. E., Burdine, L., Rogers, L. J., Morehead, L. C., Fil, D., Barker, M., Rainwater, R. R., Waldrip, Z. J., Koss, B., Burdine M. S., Chemical inhibition of DNA-PKcs impairs the activation and cytotoxicity of CD4+ helper and CD8+ effector T cells. Immunology & Cell Biology. (2023)
Guzman, G., Reed M. R., Bielamowicz, K., Koss, B., Rodriguez, A. CAR-T Therapies in solid tumors: Opportunities and challenges. Current Oncology Reports, 1-11 (2023)
Choudhury S. R., Heflin B., Taylor, E., Koss, B., Avaritt, N. L., Tackett, A. J. CRISPR/dCas9-KRAB-Mediated Suppression of S100b Restores p53-Mediated Apoptosis in Melanoma Cells. Cells 12 (5), 730 (2023)
Trentzsch, M.; Nyamugenda, E.; Miles, T. K.; Griffin, H.; Russell, S.; Koss, B.; Cooney, K. A.; Phelan, K. D.; Tackett A. J., Iyer, S.; Boysen, G.; Baldini, G. Delivery of phosphatidylethanolamine blunts stress in hepatoma cells exposed to elevated palmitate by targeting the endoplasmic reticulum. Cell Death Discovery 6:8 (2020).
Taylor, E.; Koss, B.; Davis L. E.; Tackett, A. J. Histone Modifications as Biomarkers for Immunotherapy. Methods in Molecular Biology 2055:213-228 (2019).
Chiang, T.; Koss, B.; Su, L. J.; Washam, C. L.; Byrum, S. D.; Storey, A.; Tackett, A. J. Effect of sulforaphane and 5-aza-2’-deoxycytidine on melanoma cell growth. Medicines 6, 71 (2019).
Lee, T.; Christov, P. P.; Shaw, S.; Tarr, J. C.; Zhao, B.; Veerasamy, N.; Jeon, K. O.; Mills, J. J.; Bian, Z.; Sensintaffar, J. L.; et. al. Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors That Demonstrate in Vivo Activity in Mouse Xenograft Models of Human Cancer. Journal of medicinal chemistry 62, 3971–3988 (2019).
Ren, Z.; Ahn, J. H.; Liu, H.; Tsai, Y.-H.; Bhanu, N. V; Koss, B.; Allison, D. F.; Ma, A.; Storey, A. J.; Wang, P. PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation. Blood blood-2019000578 (2019).
Shields, B. D.; Mahmoud, F.; Taylor, E. M.; Byrum, S. D.; Sengupta, D.; Koss, B.; Baldini, G.; Ransom, S.; Cline, K.; Mackintosh, S. G. Indicators of responsiveness to immune checkpoint inhibitors. Scientific Reports 7, 807 (2017).
Lee, T.; Bian, Z.; Zhao, B.; Hogdal, L. J.; Sensintaffar, J. L.; Goodwin, C. M.; Belmar, J.; Shaw, S.; Tarr, J. C.; Veerasamy, N.; Matulis, S. M.; Koss, B.; Fischer, M. A.; Arnold, A. L.; Camper, D. V.; Browning, C. F.; Rossanese, O. W.; Budhraja, A.; Opferman, J.; Boise, L. H.; Savona, M. R.; Letai, A.; Olejniczak, E. T.; Fesik, S. W. Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors. FEBS Letters 591, 240–251 (2017).
Koss, B.; Ryan, J.; Budhraja, A.; Szarama, K.; Yang, X.; Bathina, M.; Cardone, M. H.; Nikolovska-Coleska, Z.; Letai, A.; Opferman, J. T. Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines. Oncotarget 7, (2016).
Haverkamp, J. M.; Smith, A. M.; Weinlich, R.; Dillon, C. P.; Qualls, J. E.; Neale, G.; Koss, B.; Kim, Y.; Bronte, V.; Herold, M. J.; Green, D. R.; Opferman, J. T.; Murray, P. J. Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways. Immunity 41, 947–959 (2014).
Koss, B.; Morrison, J.; Perciavalle, R. M.; Singh, H.; Rehg, J. E.; Williams, R. T.; Opferman, J. T. Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia. Blood 122, 1587–1598 (2013).
Tripathi, P.; Koss, B.; Opferman, J. T.; Hildeman, D. A. Mcl-1 antagonizes Bax/Bak to promote effector CD4(+) and CD8(+) T-cell responses. Cell death and differentiation 20, 998–1007 (2013).
Wang, X.; Bathina, M.; Lynch, J.; Koss, B.; Calabrese, C.; Frase, S.; Schuetz, J. D.; Rehg, J. E.; Opferman, J. T. Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction. Genes and Development 27, 1351–1364 (2013).
Cohen, N. A.; Stewart, M. L.; Gavathiotis, E.; Tepper, J. L.; Bruekner, S. R.; Koss, B.; Opferman, J. T.; Walensky, L. D. A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival. Chemistry and Biology 19, 1175–1186 (2012).
Perciavalle, R. M.; Stewart, D. P.; Koss, B.; Lynch, J.; Milasta, S.; Bathina, M.; Temirov, J.; Cleland, M. M.; Pelletier, S.; Schuetz, J. D.; Youle, R. J.; Green, D. R.; Opferman, J. T. Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nature Cell Biology 14, 575–583 (2012).
Stewart, D. P.; Koss, B.; Bathina, M.; Perciavalle, R. M.; Bisanz, K.; Opferman, J. T. Ubiquitin-independent degradation of antiapoptotic MCL-1. Molecular and cellular biology 30, 3099–3110 (2010).