Biology subjects

Pradeep, D.

Publications and source records attributed to Pradeep, D..

3 recordsLinked to original sources

bioRxiv2026

Loss of Mast cells and histaminergic signaling link diet to platelet-mediated NETosis and mammary cancer recurrence

Breast cancer recurrence remains a clinical challenge. The period after the treatment of the primary tumor while cancer cells that evaded initial treatment lay dormant, provides a unique window of opportunity for interventions to prevent recurrence. Specific modifiable factors such as consumption of high fat diets or elevated circulating cholesterol are associated with decreased time to recurrence. Mechanistically, oxidized cholesterol and lipid species have been implicated in the regulation of the tumor microenvironment. This suggests that consumption of food prepared under oxidizing conditions such as pan-frying, may be an underappreciated risk. Using murine models of mammary cancer dormancy, we found that a diet enriched with fat from fried, cured bacon (cfBF) decreased dormancy latency times. Resulting lesions had fewer mast cells (MCs). Loss of MCs alone resulted in reemergence from dormancy. Elevated expression of a MC gene signature in breast tumors was associated with improved progression free and overall survival, highlighting the human relevance of these findings. MCs are a major source of tissue histamine, and lesions from mice fed cfBF had decreased concentrations. Importantly, antagonists of the histamine receptor 2 (H2R) sparked reemergence from dormancy. H2R antagonists are over-the-counter drugs are taken to alleviate gastroesophageal reflux disease. Chronic treatment of mice with H2R-antagonists sensitized platelets towards activation and crosstalk with neutrophils, and subsequent formation of neutrophil extracellular traps (NETs). The loss of platelet or NETosis activity mitigated the H2R-antagonist stimulated reemergence from dormancy. Therefore, we establish a novel metastatic axis which links diet to recurrence via MCs, histaminergic signaling and NETosis: Diet -- MC -- H2R -- (decreased) Platelet Activity -- (decreased) Neutrophil-NETosis -- (decreased) Reemergence from Dormancy. Our data reveal several potential intervention strategies: lifestyle, MC stabilization, histaminergic signaling, and neutrophil and platelet activity.

cancer biology↗

bioRxiv2025

The JAW-TCP-FUL genetic axis triggers an early reorientation of cell anisotropy to initiate and drive fertilization-dependent fruit elongation in Arabidopsis

In angiosperms, the ovary grows and develops into a fruit after fertilization, and the seeds are formed within to ensure reproductive success. Although genetic regulators suppressing fertilization-independent fruit growth or parthenocarpy have been identified in the Brassicaceae model Arabidopsis thaliana, the fertilization-dependent activator of fruit growth has not been elucidated. Here, we show that the miR319-regulated TCP transcription factors (JAW-TCPs) directly activate the transcription of the FRUITFULL (FUL) gene and promote fruit morphogenesis. By activating FUL, JAW-TCPs indirectly repress the four valve-margin specifying genes SHATTERPROOF1, SHATTERPROOF2, INDEHISCENT and ALCATRAZ in the valves. Mutating these genes suppresses defects caused by the combined loss of JAW-TCPs and FUL. Through extensive confocal imaging studies, we deciphered the cellular basis of JAW-TCP function revealing that JAW-TCPs promote fruit elongation by triggering the reorientation of cell anisotropy along the length axis at an early growth stage after fertilization. Our study uncovers a fertilization-dependent genetic module driving fruit elongation and sets the stage to identify other genetic regulators in this pathway.

plant biology↗

bioRxiv2025

Cholesterol efflux protein, ABCA1, supports anti-cancer functions of myeloid immune cells

Although immune therapy has seen significant advances, the majority of breast and other solid tumors do not respond or quickly develop de novo resistance. One factor driving resistance is highly immune suppressive myeloid cells (MCs) such as macrophages. Previous work has established clinical links between cholesterol and cancer outcome, and that MC function can be regulated through disruption in cholesterol metabolism. Thus, we screened for proteins that were expressed in MCs, involved in cholesterol homeostasis and whose expression was associated with survival; we identify the cholesterol efflux protein ABCA1. Preclinical studies revealed that ABCA1 activity resulted in increased anti-cancer functions of macrophages: enhanced tumor infiltration, decreased angiogenic potential, reduced efferocytosis, and improved support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K dependent and independent mechanisms. Assessment of human blood and breast tumors revealed correlations between ABCA1 in macrophages and angiogenic potential, VEGFA, and CD8 T cell abundance and activity, highlighting the clinical relevance of our findings. The culmination of the effects of ABCA1 on MC function were demonstrated through increased tumor growth and metastasis in mice with MC specific knockout of ABCA1. Therefore, modulating ABCA1 activity within MCs may represent a novel approach to immune therapy.

cancer biology↗