Recent Publications
Scharping, N.E., Ge, X., Matias, M.I., Jiang, F., Cafferata, A., Heeg, M., Monell, A., Galletti, G., Cheung, K.P., Rock, A., Thao, N., Shuttleworth, S.L., Bauer, M.A., Takehara, K.K., Ferry, A., Quon, S., Koss, B., Myers, S.A., Bennett, E.J., Goldrath, A. Proteostasis sustains T cell differentiation potential and tumor-infiltrating lymphocyte function. Cell, 189(10), 2857-2874 (2026).
Edmondson, J. L., Reed, M. R., Fil, D., Heflin, B., McKinnon, A., Bauer, M. A., Morehead, L. C., Avaritt, N. L., Phillips, M., Taverna, S. D., Tackett, A. J., Koss, B. EZH2 loss during metabolic stress drives restoration of MHC Class I machinery in melanoma. iScience, 2025; 28.
This study demonstrates that loss of EZH2 under conditions of metabolic stress leads to restored expression of MHC Class I antigen presentation machinery in melanoma cells. These findings reveal a previously unrecognized link between epigenetic regulation and immune control of tumors under nutrient-limited conditions.
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
Rainwater RR, Azevedo-Pouly AC, Waldrip ZJ, Hicks BH, Callais NA, Koss B, Storey AJ, Burdine L, Burdine MS. DNA-PKcs controls the cytotoxic T cell response to cancer and transplant allograft through regulating LAT-dependent signaling. Cell Rep. 2026;45(1):116796.
Xia J, Zhao H, Edmondson JL, Koss B, Zhan F. Role of NEK2 in tumorigenesis and tumor progression. Trends Mol Med. 2025;31(1):79-93.
Kelliher JL, Folkerts ML, Shen KV, Song W, Tengler K, Stiefel CM, Lee SO, Dray E, Zhao W, Koss B, Pannunzio NR, Leung JW. Evolved histone tail regulates 53BP1 recruitment at damaged chromatin. Nat Commun. 2024;15(1):4634.
Frett B, Stephens KE, Koss B, Melnyk S, Farrar J, Saha D, Roy Choudhury S. Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia. Cancer Sci. 2024;115(3):963-973.
Morehead LC, Koss B, Fil D, Heflin B, Garg S, Wallis KF, Tackett AJ, Miousse IR. Resveratrol induces major histocompatibility complex class I antigen presentation in a STING-dependent and independent manner in melanoma. Mol Immunol. 2023 Nov;163:188-195.
Azevedo-Pouly AC, Appell LE, Burdine L, Rogers LJ, Morehead LC, Fil D, Barker M, Rainwater RR, Waldrip ZJ, Koss B, Burdine MS. Chemical inhibition of DNA-PKcs impairs the activation and cytotoxicity of CD4+ helper and CD8+ effector T cells. Immunol Cell Biol. 2023;101(7):663-671.
Guzman G, Reed MR, Bielamowicz K, Koss B, Rodriguez A. CAR-T Therapies in Solid Tumors: Opportunities and Challenges. Curr Oncol Rep. 2023;25(5):479-489.
Roy Choudhury S, Heflin B, Taylor E, Koss B, Avaritt NL, Tackett AJ. CRISPR/dCas9-KRAB-Mediated Suppression of S100b Restores p53-Mediated Apoptosis in Melanoma Cells. Cells. 2023;12(5):730.
Koss B, Shields BD, Taylor EM, Storey AJ, Byrum SD, Gies AJ, Washam CL, Choudhury SR, Hyun Ahn J, Uryu H, Williams JB, Krager KJ, Chiang TC, Mackintosh SG, Edmondson RD, Aykin-Burns N, Gajewski TF, Wang GG, Tackett AJ. Epigenetic Control of Cdkn2a.Arf Protects Tumor-Infiltrating Lymphocytes from Metabolic Exhaustion. Cancer Res. 2020;80(21):4707-4719.
Trentzsch M, Nyamugenda E, Miles TK, Griffin H, Russell S, Koss B, Cooney KA, Phelan KD, Tackett AJ, 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 Discov. 2020;6:8.
Taylor EM, Koss B, Davis LE, Tackett AJ. Histone Modifications as Biomarkers for Immunotherapy. Methods Mol Biol. 2020;2055:213-228.
Chiang TC, Koss B, Su LJ, Washam CL, Byrum SD, Storey A, Tackett AJ. Effect of Sulforaphane and 5-Aza-2'-Deoxycytidine on Melanoma Cell Growth. Medicines (Basel). 2019 Jun 27;6(3):71.
Lee T, Christov PP, Shaw S, Tarr JC, Zhao B, Veerasamy N, Jeon KO, Mills JJ, Bian Z, Sensintaffar JL, Arnold AL, Fogarty SA, Perry E, Ramsey HE, Cook RS, Hollingshead M, Davis Millin M, Lee KM, Koss B, Budhraja A, Opferman JT, Kim K, Arteaga CL, Moore WJ, Olejniczak ET, Savona MR, Fesik SW. Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors That Demonstrate in Vivo Activity in Mouse Xenograft Models of Human Cancer. J Med Chem. 2019;62(8):3971-3988.
Ren Z, Ahn JH, Liu H, Tsai YH, Bhanu NV, Koss B, Allison DF, Ma A, Storey AJ, Wang P, Mackintosh SG, Edmondson RD, Groen RWJ, Martens AC, Garcia BA, Tackett AJ, Jin J, Cai L, Zheng D, Wang GG. PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation and broad H3K27me3 domain formation. Blood. 2019;134(14):1176-1189.
Shields BD, Koss B, Taylor EM, Storey AJ, West KL, Byrum SD, Mackintosh SG, Edmondson R, Mahmoud F, Shalin SC, Tackett AJ. Loss of E-Cadherin Inhibits CD103 Antitumor Activity and Reduces Checkpoint Blockade Responsiveness in Melanoma. Cancer Res. 2019;79(6):1113-1123.
Shields BD, Mahmoud F, Taylor EM, Byrum SD, Sengupta D, Koss B, Baldini G, Ransom S, Cline K, Mackintosh SG, Edmondson RD, Shalin S, Tackett AJ. Indicators of responsiveness to immune checkpoint inhibitors. Sci Rep. 2017 Apr 11;7(1):807.
Lee T, Bian Z, Zhao B, Hogdal LJ, Sensintaffar JL, Goodwin CM, Belmar J, Shaw S, Tarr JC, Veerasamy N, Matulis SM, Koss B, Fischer MA, Arnold AL, Camper DV, Browning CF, Rossanese OW, Budhraja A, Opferman J, Boise LH, Savona MR, Letai A, Olejniczak ET, Fesik SW. Discovery and biological characterization of potent myeloid cell leukemia-1 inhibitors. FEBS Lett. 2017;591(1):240-251.
Koss B, Ryan J, Budhraja A, Szarama K, Yang X, Bathina M, Cardone MH, Nikolovska-Coleska Z, Letai A, Opferman JT. Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines. Oncotarget. 2016;7(10):11500-11.
Haverkamp JM, Smith AM, Weinlich R, Dillon CP, Qualls JE, Neale G, Koss B, Kim Y, Bronte V, Herold MJ, Green DR, Opferman JT, Murray PJ. Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways. Immunity. 2014;41(6):947-59.
Koss B, Morrison J, Perciavalle RM, Singh H, Rehg JE, Williams RT, Opferman JT. Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia. Blood. 2013;122(9):1587-98.
Tripathi P, Koss B, Opferman JT, Hildeman DA. Mcl-1 antagonizes Bax/Bak to promote effector CD4(+) and CD8(+) T-cell responses. Cell Death Differ. 2013;20(8):998-1007.
Wang X, Bathina M, Lynch J, Koss B, Calabrese C, Frase S, Schuetz JD, Rehg JE, Opferman JT. Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction. Genes Dev. 2013;27(12):1351-64.
Cohen NA, Stewart ML, Gavathiotis E, Tepper JL, Bruekner SR, Koss B, Opferman JT, Walensky LD. A competitive stapled peptide screen identifies a selective small molecule that overcomes MCL-1-dependent leukemia cell survival. Chem Biol. 2012;19(9):1175-86.
Perciavalle RM, Stewart DP, Koss B, Lynch J, Milasta S, Bathina M, Temirov J, Cleland MM, Pelletier S, Schuetz JD, Youle RJ, Green DR, Opferman JT. Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nat Cell Biol. 2012;14(6):575-83.
Stewart DP, Koss B, Bathina M, Perciavalle RM, Bisanz K, Opferman JT. Ubiquitin-independent degradation of antiapoptotic MCL-1. Mol Cell Biol. 2010;30(12):3099-110.