Biology subjects

Elsamanoudi, S.

Publications and source records attributed to Elsamanoudi, S..

3 recordsLinked to original sources

bioRxiv2026

Spatial epigenomics reveals ancestry-associated regulatory states linked to aggressive prostate cancer biology

Prostate cancer (PCa) exhibits substantial biological heterogeneity, including population associated differences in tumor aggressiveness and clinical outcomes. Although socioeconomic and environmental factors contribute to these disparities, intrinsic tumor regulatory programs may also influence disease behavior. Here, we investigated whether differences in chromatin regulation contribute to distinct tumor states in Black and White men with localized PCa. We performed spatial chromatin accessibility profiling (ATAC-seq) of prostatectomy specimens from Black and White patients receiving equal healthcare access at the Center for Prostate Disease Research (USUHS) and Walter Reed National Military Medical Center. Tumors showed distinct chromatin accessibility landscapes between the two populations, with tumors from Black patients exhibiting reduced accessibility of motifs associated with the chromatin architectural regulator CTCF and enrichment of motifs linked to epithelial-mesenchymal transition and inflammatory programs. Reduced CTCF expression was independently validated by immunohistochemistry in 99 prostatectomy specimens. These findings identify population-associated differences in chromatin regulation in localized PCa and suggest that altered CTCF-associated regulation, inflammatory signaling, and epithelial plasticity may contribute to the biological heterogeneity underlying ancestry-dependent PCa disparities.

cancer biology↗

bioRxiv2026

Stage-Specific Regulation of DNA Damage Repair by the Circadian Regulator, CRY1, in Prostate Cancer

Circadian dysregulation is increasingly linked to prostate cancer (PCa) progression, yet its role in directing DNA damage response (DDR) pathway selection remains poorly understood. Here, we identify circadian cryptochrome 1 (CRY1), a core circadian regulator, as a stage-specific determinant of DDR dependencies. Integrated transcriptomic and CRISPR-based analyses reveal that CRY1 promotes non-homologous end joining (NHEJ) and base excision repair (BER)-associated programs in hormone-sensitive disease (HTS), while driving a switch toward homologous recombination (HR) dependency in castration-resistant prostate cancer (CRPC). Mechanistically, CRY1 couples proliferative signaling to genome maintenance, enabling tumor cells to tolerate genotoxic stress and sustain progression. Notably, loss of CRY1 exposes distinct, context-dependent DDR vulnerabilities, revealing repair plasticity as a targetable actionable feature of disease evolution. These findings position CRY1 as a central regulator of DDR rewiring and support CRY1-directed combination strategies with DDR inhibitors as a rationale to delay or prevent progression to advanced, treatment-resistant PCa.

cancer biology↗

bioRxiv2025

Integrated proteogenomics uncovers ancestry-specific and shared molecular drivers in localized prostate cancer

Our integrative proteogenomics (genome, proteome and phosphoproteome) of localized prostate cancer (PCa) in an equal-access Military Health System patient cohort (57 Black and 55 White) revealed significant ancestry-associated differences. Somatic and germline regulatory differences converged on androgen, metabolic, PI3K/AKT/mTOR, and DNA damage response (DDR) pathways, with ancestry-specific immune- and stromal-associated signals. Black patients displayed greater genomic variability, enhanced androgen response, fatty-acid metabolism, and epithelial-mesenchymal transition, while White patients showed prevalent DDRG alterations, activated oncogenic signaling (MYC, E2F, mTORC1), and cell cycle regulation. Phosphoproteomics highlighted distinct kinase activities and candidate druggable dependencies. Multiomics integration revealed three exploratory tumor subtypes whose distinct biological programs were reproducibly validated. Ancestry-associated eQTLs supported inherited regulation of the proteome independent of CNAs. Ancestry-specific CNA and protein panels improved progression risk prediction beyond PSA and pathology models. These findings provide a framework for ancestry-informed prognostic models and generate testable hypotheses for precision therapies to reduce outcome disparities.

cancer biology↗