Dibra Lab
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About
Our laboratory investigates how tumor-initiating genetic alterations, particularly mutant p53, reprogram tumor cells to evade immune surveillance in breast cancer and MASH-associated hepatocellular carcinoma. We integrate genetically engineered mouse models, single-cell and spatial profiling, and immunopeptidomic analyses to define the mechanisms by which oncogenic p53 shapes the tumor–immune microenvironment and drives resistance to T cell–based therapies. Our goal is to translate mechanistic insight into rational, immune-based combinatorial strategies for p53-mutant cancers.
Key Research Areas
Triple-Negative Breast Cancer (TNBC): We study how TP53 missense mutations drive immune escape in triple-negative breast cancer. Mutant p53 rewires transcriptional and inflammatory programs, suppresses antigen presentation, and promotes immunosuppressive microenvironments that impair CD4⁺ and CD8⁺ T cell function. Using conditional and transgenic models alongside spatial and single-cell technologies, we define how mutant p53 governs resistance to immunotherapy and identify actionable vulnerabilities that can be harnessed to improve outcomes in TNBC patients harboring TP53 mutations.
MASH-Associated Hepatocellular Carcinoma (MASH-HCC): We examine how hepatocyte-specific p53 alteration cooperates with metabolic inflammation to drive immune dysfunction and tumor progression in MASH-HCC. Our work focuses on how p53-driven programs reshape antigen presentation, hepatocyte–immune interactions, and the spatial organization of T cells during disease progression. Through physiologic diet-induced models and mechanistic perturbation studies, we aim to uncover strategies to restore effective anti-tumor immunity in liver cancer arising in the context of metabolic injury.
Current Projects
Advanced Genetic Toolkits: Integration of in vivo genetic screening platforms with spatially resolved perturbation approaches to interrogate tumor–immune interactions.
Single-Cell and Spatial Omics Technologies: Application of scRNA-seq and spatial transcriptomics to define cellular heterogeneity, lineage states, and immune niche architecture within tumors.
Oncogene-Driven Immune Evasion: Dissection of oncogene-mediated mechanisms that promote both innate and adaptive immune escape.
Immunopeptidomics: Systematic characterization of the MHC-associated immunopeptidome to identify tumor-specific antigen presentation dynamics in vivo.
Genetically Engineered Mouse Models: Use of conditional and transgenic breast cancer and MASH-HCC models to functionally test tumor–immune regulatory mechanisms in vivo.
Team
Mirza Arsalan, MS, Research TechnicianI
Tyler Owens, Lab, Research Associate II
Recent Publications
Dibra D, Xiong S, Moyer SM, El-Naggar AK, Qi Y, Su X, Kong EK, Korkut A, Lozano G. Mutant p53 protects triple-negative breast adenocarcinomas from ferroptosis in vivo. Sci Adv. 2024 Feb 16;10(7):eadk1835. doi: 10.1126/sciadv.adk1835. Epub 2024 Feb 14. PubMed PMID: 38354236; PubMed Central PMCID: PMC10866549.
Dibra D, Xiong S, Moyer SM, El-Naggar AK, Qi Y, Su X, Kong EK, Korkut A, Lozano G. Mutant p53 protects triple-negative breast adenocarcinomas from ferroptosis in vivo. Sci Adv. 2024 Feb 16;10(7):eadk1835. doi: 10.1126/sciadv.adk1835. Epub 2024 Feb 14. PubMed PMID: 38354236; PubMed Central PMCID: PMC10866549.
Dibra D, Moyer SM, El-Naggar AK, Qi Y, Su X, Lozano G. Triple-negative breast tumors are dependent on mutant p53 for growth and survival. Proc Natl Acad Sci U S A. 2023 Aug 22;120(34):e2308807120. doi: 10.1073/pnas.2308807120. Epub 2023 Aug 14. PubMed PMID: 37579145; PubMed Central PMCID: PMC10450424.
Dibra D, Mitra A, Newman M, Xia X, Cutrera JJ, Gagea M, Kleinerman ES, Lozano G, Li S. Lack of Immunomodulatory Interleukin-27 Enhances Oncogenic Properties of Mutant p53 In Vivo. Clin Cancer Res. 2016 Aug 1;22(15):3876-83. doi: 10.1158/1078-0432.CCR-15-2052. Epub 2016 Mar 15. PubMed PMID: 26979394; PubMed Central PMCID: PMC4970873.
Dibra D, Xia X, Mitra A, Cutrera JJ, Lozano G, Li S. Mutant p53 in concert with an interleukin-27 receptor alpha deficiency causes spontaneous liver inflammation, fibrosis, and steatosis in mice. Hepatology. 2016 Mar;63(3):1000-12. doi: 10.1002/hep.28379. Epub 2016 Jan 21. PubMed PMID: 26637970; PubMed Central PMCID: PMC4764463.
A more complete listing of my publications can be found here.