Rama Khokha

Mapping lineage and functional diversity of the mammary epithelium in women at high risk of breast cancer

Matthew Waas, Bowen Zhang, Meinusha Govindarajan, Pirashaanthy Tharmapalan et autres

Breast cancer risk is shaped by the vast heterogeneity of mammary epithelial cells, comprising basal, luminal progenitor, and mature luminal populations. While transcriptional variation among these lineages has been extensively studied, protein-level features—particularly in high-risk women—remain underexplored, limiting insight into early cellular …

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Germline BRCA1 Mutation Deregulates Irradiation–Induced Cell Cycle Checkpoints in Human Mammary Luminal Progenitors

Abhijith Kuttanamkuzhi, Bowen Zhang, Kelvin Yeung, Matthew Waas et autres

Abstract Mammary ductal tree comprises two epithelial lineages, basal and luminal, which harbour stem and progenitor cell subsets essential to breast physiology and are cancer-initiating precursors. Dysregulated cellular stress response is an early event in tumorigenesis, yet lineage-rooted study of primary breast …

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Abstract 6019: Fatty acid exposure promotes age-related mammary tissue alterations with pro-tumorigenic potential

Mariana Bustamante Eduardo, Abul B.M.M.K. Islam, Curtis W. McCloskey, María Paula Zappia et autres

Abstract Introduction: Exposure of non-transformed breast cells and breast microstructures to the medium-chain (MC) fatty acid (FA) octanoic acid (OA) induces a metabolic shift toward the serine, one-carbon, glycine and methionine pathways (SOG/methionine), enhancing epigenetic plasticity, increasing reactive oxygen species (ROS), promoting …

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Pan-cancer N-glycoproteomic atlas of patient-derived xenografts uncovers FAT2 as an actionable surface target

Meinusha Govindarajan, Salvador Mejia-Guerrero, Shawn C. Chafe, Shahbaz Khan et autres

Cell surface proteins offer significant cancer therapeutic potential attributable to their accessible membrane localization and central roles in cellular signaling, yet their promise remains largely untapped due to technical challenges inherent to profiling them. Here, we employ N-glycoproteomics to analyze 85 patient-derived …

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Mapping lineage and functional diversity in the high-risk human mammary epithelium

Matthew Waas, Bowen Zhang, Meinusha Govindarajan, Pirashaanthy Tharmapalan et autres

Abstract Background Breast cancer risk is shaped by the vast heterogeneity of mammary epithelial cells, comprising basal, luminal progenitor, and mature luminal populations. While transcriptional variation among these lineages has been extensively studied, protein-level features - particularly in high-risk women - remain …

ca (code pays fourni par la source)

MassIVE MSV000101472 - Germline BRCA1 Mutation Deregulates DNA Damage Induced Cell Cycle Checkpoint Activation in Human Mammary Luminal Progenitors

Shane M. Harding, Dr. Thomas Kislinger, Rama Khokha

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Anti-progestin therapy targets hallmarks of breast cancer risk

Bruno M. Simões, Robert Pedley, Curtis W. McCloskey, Matthew Roberts et autres

Abstract Breast cancer is the leading cause of cancer-related death in women worldwide 1 . Here, in the Breast Cancer-Anti-Progestin Prevention Study 1 (BC-APPS1; NCT02408770 ), we assessed whether progesterone receptor antagonism with ulipristal acetate for 12 weeks reduces surrogate markers of …

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Estrogen Receptor α-Mediated Sex-Specific Immune Modulation and Tumor Regulation in Pancreatic Cancer

Niklas Krebs, Kazeera Aliar, Foram Fyas, Jillian R. Brown et autres

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Medium-Chain Fatty Acid exposure in non-transformed mammary glands leads to pro-tumorigenic alterations associated with aging

Mariana Bustamante Eduardo, Abul Bashar Mir Md. Khademul Islam, Curtis W. McCloskey, María Paula Zappia et autres

Abstract The local breast environment is a valuable research focus for identifying the etiological and biological factors that contribute to the development of breast cancer. Single-cell RNA sequencing shows that the increased availability of the medium-chain fatty acid octanoic acid induces changes …

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The histone lysine methyltransferase NSD3 drives osteosarcomagenesis by inactivating ARID3A

Jinchang Lu, Yang Shao, Sanjay Saw, Hui Fang et autres

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Tumour tissue: heterogeneous, but not disordered

Barbara T. Grünwald, Rama Khokha

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Abstract P1-05-02: Medium chain fatty acids shift metabolism towards the de novo serine pathway fostering epigenetic plasticity and oxidative DNA damage

Mariana Bustamante Eduardo, Curtis W. McCloskey, Gannon Cottone, Shiyu Liu et autres

Abstract Introduction: We have investigated the breast microenvironment to identify factors that promote Estrogen Receptor Negative Breast Cancer (ERneg BC) and that may be disrupted for prevention. To that end, we have identified a lipid metabolism gene signature associated with the risk …