Biology subjects

Datta, K. K.

Publications and source records attributed to Datta, K. K..

5 recordsLinked to original sources

bioRxiv2026

Sex differences in cardiomyocyte proteomic responses to the cardiotoxic chemotherapy drug doxorubicin

Anthracyclines, including doxorubicin, are widely used chemotherapeutic agents, but dose-dependent cardiotoxicity limits their clinical utility and increases the risk of heart failure in cancer survivors. In paediatric patients, female sex is a significant risk factor for anthracycline-associated cardiotoxicity, yet pre-clinical studies rarely investigate sex differences in immature hearts. Here, we provide a proteomic dataset from primary cardiomyocytes, isolated from postnatal day 2 rat hearts and treated with a clinically relevant concentration of doxorubicin. Analysis of proteins present in all samples identified candidates previously shown to be regulated by doxorubicin in adult hearts, as well as candidates that may be specifically regulated in young hearts. This dataset provides a resource for generating hypotheses on molecular mechanisms contributing to sex differences in juvenile doxorubicin-induced cardiotoxicity.

molecular biology↗

bioRxiv2025

Uncovering Shared and Tissue-Specific Molecular Adaptations to Intermittent Fasting in Liver, Brain, and Muscle

Intermittent fasting (IF) has emerged as a powerful dietary intervention with profound metabolic benefits, yet the tissue-specific molecular mechanisms underlying these effects remain poorly understood. In this study, we employed comprehensive proteomics and transcriptomics analysis to investigate the systemic and organ-specific adaptations to IF in male C57BL/6 mice. Following a 16-hour daily fasting regimen (IF16) over four months, IF reduced blood glucose, HbA1c, and cholesterol levels while increasing ketone bodies, indicative of enhanced metabolic flexibility. Proteomic profiling of the liver, skeletal muscle, and cerebral cortex revealed tissue-specific responses, with the liver exhibiting the most pronounced changes, including upregulation of pathways involved in fatty acid oxidation, ketogenesis, and glycan degradation, and downregulation of steroid hormone and cholesterol metabolism. In muscle, IF enhanced pyruvate metabolism, fatty acid biosynthesis, and AMPK signaling, while suppressing oxidative phosphorylation and thermogenesis. The cerebral cortex displayed unique adaptations, with upregulation of autophagy, PPAR signaling, and metabolic pathways, and downregulation of TGF-beta and p53 signaling, suggesting a shift toward energy conservation and stress resilience. Notably, Serpin A1c emerged as the only protein commonly upregulated across all three tissues, highlighting its potential role in systemic adaptation to IF. Integrative transcriptomic and proteomic analyses revealed partial concordance between mRNA and protein expression, underscoring the complexity of post-transcriptional regulation. Shared biological signaling processes were identified across tissues, suggesting unifying mechanisms linking metabolic changes to cellular communication. Our findings reveal both conserved and tissue-specific responses by which IF may optimize energy utilization, enhance metabolic flexibility, and promote cellular resilience.

molecular biology↗

bioRxiv2025

EPHA2-dependent Ephrin-B1 signaling supports self-renewal ability and recurrence of oral cancer

Eph-Ephrin pathway that drives a bidirectional signaling regulates a plethora of biological activities with its varied level of complexity. While the canonical trans-interaction of the ligand and receptor on neighboring cells initiates forward signaling that brings about biological activities, their cis-interaction on the same cell attenuates the forward signaling, modulating the biological effects. Yet, non-canonical cis-interactions with heterotypic surface proteins and kinases regulate certain biological effects. In cancer, the canonical signaling is believed to be tumor suppressive, while the ligand-independent non-canonical signaling drives tumor progression and poor prognosis. Self-renewal ability of cancer cells is a major underlying cause of recurrence and poor prognosis of cancer. Using SILAC-based proteomics, we identified Ephrin-B1 signaling as a crucial regulator of oral cancer self-renewal. Though Ephrin-B1 is known to regulate normal stem cells, its role in cancer remains underexplored. Our biochemical analyses show that Ephrin-B1 binds to a nonconventional receptor EPHA2, which is known to regulate cancer stem cells (CSCs), though the mechanism is less explored. Contrary to the belief that the cis-interaction of receptors and ligands is a means to block functional signaling, our immunoprecipitation, FRET facilitated photoswitching analysis, proximity ligation assay, and in vitro kinase assay provide evidence for the Ephrin-B1-EPHA2 cis-interaction leading to the phosphorylation of EphrinB1 at Y324/329 and Y317. Extreme limiting dilution assay in vitro and in vivo confirmed that this cis-interaction promotes CSC enrichment. Substantiating our in vitro results, mouse orthotopic models showed that Ephrin-B1/EPHA2 interaction regulates prognosis. The clinical relevance of the finding was validated using a TCGA data set and immunohistochemical analysis of tissue microarray using samples from oral cancer patients with recurrence in comparison to patients, who showed disease-free survival. Given that Ephrin-B interacts with EphB for normal stem cell homeostasis, this unconventional EPHA2/Ephrin-B1 cis-interaction, specifically manifested in CSC niches, might serve as an attractive target for therapy, warranting further validation.

cancer biology↗

bioRxiv2019

Marizomib suppresses triple-negative breast cancer via proteasome and oxidative phosphorylation inhibition

Lacking effective targeted therapies, triple-negative breast cancer (TNBCs) is highly aggressive with development of metastasis especially brain, and remains clinically challenging breast cancer subtype to treat. Despite the survival dependency on the proteasome pathway genes, FDA-approved proteasome inhibitors induced minimal clinical response in breast cancer patients due to weak proteasome inhibition. Here, we show that a potent proteasome inhibitor Marizomib (Mzb) inhibits multiple proteasome catalytic activities and induces a better anti-tumor response in TNBC cell lines and patient-derived xenografts alone and in combination with the standard-of-care chemotherapy. Mechanistically, Mzb inhibits oxidative phosphorylation (OXPHOS) via PGC-1 suppression in conjunction with proteasome inhibition in TNBC cells. Mzb reduces lung and brain metastases by reducing the number of circulating tumor cells and the expression of multiple genes involved in the epithelial-to-mesenchymal transition. Furthermore, Mzb-induced OXPHOS inhibition upregulates glycolysis to meet the energetic demands of TNBC cells and, hence, combined inhibition of glycolysis with Mzb exposure leads to a synergistic anti-cancer activity. Collectively, our data provide a strong rationale for a clinical evaluation of Mzb in primary and metastatic TNBC patients.\n\nOne Sentence SummaryMarizomib inhibits primary tumor growth, and also reduces lung and brain metastases in pre-clinical models of triple-negative breast cancer.

cancer biology↗

bioRxiv2019

Proteome-wide characterization and biomarker identification of intracranial aneurysm

The scientific basis of intracranial aneurysm (IA) formation, its rupture and further development of cerebral vasospasm remains incompletely understood. Deciphering the molecular mechanisms underlying these events will lead to identification of early detection biomarkers and in turn, improved treatment outcomes. Aberrant protein expression may drive structural alterations of vasculature found in IA. To unravel these aberrations, we performed untargeted, global, quantitative proteomic analysis of aneurysm tissue and serum from patients with IA. Samples were derived from patients of three clinical sub groups- 1) unruptured aneurysm 2) ruptured aneurysm without vasospasm 3) ruptured aneurysm who developed vasospasm. A total of 937 and 294 proteins were identified in aneurysm tissue and serum samples respectively. Several proteins that are known to maintain the structural integrity of vasculature were found to be dysregulated. ORM1, a glycoprotein, was significantly upregulated in both the aneurysm tissue and serum samples of unruptured IA patients. We employed a larger cohort of patients and validated ORM1 as a potential biomarker for screening of unruptured aneurysm using ELISA. Samples from ruptured aneurysm with vasospasm showed significant upregulation of MMP9 as compared to ruptured aneurysm without vasospasm. Using a cohort of ruptured aneurysm patients with and without vasospasm, we validated MMP9 as a potential biomarker for vasospasm. This study reveals pathophysiology underlying different clinical sub groups of IA and also suggests potential biomarkers.

neuroscience↗