Biology subjects

Rusan, N.

Publications and source records attributed to Rusan, N..

4 recordsLinked to original sources

bioRxiv2026

Tumor-Associated Macrophages Promote Brain Metastasis

Brain metastasis affects 20-40% of cancer patients and remains largely incurable, yet how metastatic cells engage and remodel brain-barrier interfaces is poorly understood. This gap stems in large part from the scarcity of genetically tractable in vivo systems that can resolve tumor-host interactions in their native context. Although tumor-associated macrophages (TAMs) dominate the brain metastatic microenvironment, their causal contribution to colonization has been difficult to establish. Here, we develop the adult Drosophila brain as a platform to address these questions, using allograft transplantation of lgl-/- neural stem cell-derived tumors. We find that tumors colonize the brain surface and deform it through collective, sheet-like invasion, recapitulating features of human leptomeningeal disease without parenchymal infiltration. While tumors compromise both functional and structural integrity of blood-brain barrier, they fail to breach the basement membrane (BM), which we identify as the principal barrier restricting invasion. Critically, tumors recruit TAMs to the metastasized tumor, and genetic depletion of TAMs markedly reduces brain metastasis without affecting initial dissemination. This establishes a causal role for macrophages in brain colonization, potentially through BM remodeling. Together, these findings reveal a conserved, macrophage-dependent mechanism of brain metastasis and provide a genetically accessible model that fills a critical gap in the field.

Cancer Biology↗

bioRxiv2025

An intrinsically disordered region of Drosha selectively promotes miRNA biogenesis, independent of tissue-specific Microprocessor condensates

Precise control of miRNA biogenesis is of extreme importance, since mis-regulation of miRNAs underlies or exacerbates many disease states. The Microprocessor complex, composed of DROSHA and DGCR8, carries out the first cleavage step in canonical miRNA biogenesis. Despite recent advances in understanding the molecular mechanism of Microprocessor, the N-terminal region of DROSHA is less characterized due its high intrinsic disorder. Here we demonstrate that Microprocessor forms condensates with properties consistent with liquid-liquid phase separation (LLPS) in select tissues in C. elegans. While DRSH-1/Drosha recruitment to granules is only partially dependent on its intrinsically disordered regions (IDRs), one of these N-terminal IDRs is crucial for biogenesis of a subset of miRNAs and normal development. A cis region of IDR-dependent miRNAs confers IDR-dependence to another miRNA, suggesting that the IDR recognizes sequences or structures in the miRNA primary transcript. Future studies will further elucidate the specificity of this interaction and the putative role of Microprocessor condensates.

molecular biology↗

bioRxiv2024

A deficiency screen identifies genomic regions critical for sperm head-tail connection

A stable connection between the sperm head and tail is critical for fertility in species with flagellated sperm. The head-tail coupling apparatus (HTCA) serves as the critical link between the nucleus (head) and the axoneme (tail) via the centriole. To identify regions of the Drosophila melanogaster genome that contain genetic elements that influence HTCA formation, we undertook a two part screen using the Drosophila deficiency (Df) kit. For this screen, we utilized a sensitized genetic background that overexpresses the pericentriolar material regulatory protein Pericentrin-Like Protein (PLP). We had previously shown that PLP overexpression (PLPOE) disrupts the head-tail connection in some spermatids, but not to a degree sufficient to reduce fertility. In the first step of the screen we tested for Dfs that in combination with PLPOE cause a reduction in fertility. We ultimately identified 11 regions of the genome that showed an enhanced fertility defect when combined with PLP overexpression. In the second step of the screen we tested these Dfs for their ability to enhance the HTCA defect caused by PLPOE, finding six. We then tested smaller Dfs to narrow the region of the genome that contained these enhancers. To further analyze the regions of the genome removed by these Dfs, we examined the expression patterns of the genes within these Dfs in publicly available datasets of RNAseq of Drosophila tissues and snRNAseq of Drosophila testes. In total, our analysis suggests that some of these Dfs may contain a single gene that might influence HTCA formation and / or fertility, while others appear to be regions of the genome especially rich in testis-expressed genes that might affect the HTCA because of complex, multi-gene interactions. Article SummaryWe perform a genetic enhancer deficiency screen to uncover genomic regions required for proper sperm head-tail connection. We identified 6 regions and provide insight into these regions using publicly available RNA sequence data. Our data reveal that these regions are exceptionally rich in testes specific genes. Further analysis using small deficiencies resulted in two classes of enhancers: one class likely enhances head-tail connection by disrupting multiple genes, while the second class might house a single gene responsible for the reduction in fertility.

genetics↗

bioRxiv2020

Host autophagy mediates organ wasting and nutrient mobilization for tumor growth

During tumor growth - when nutrient and anabolic demands are high - autophagy supports tumor metabolism and growth through lysosomal organelle turnover and nutrient recycling1. Ras-driven tumors additionally invoke non-autonomous autophagy in the microenvironment to support tumor growth, in part through transfer of amino acids2-4. Here we uncover a third critical role of autophagy in mediating systemic organ wasting and nutrient mobilization for tumor growth using a well-characterized malignant tumor model in Drosophila melanogaster. Micro-computed X-ray tomography and metabolic profiling reveal that RasV12; scrib-/- tumors grow 10-fold in volume, while systemic organ wasting unfolds with progressive muscle atrophy, loss of body mass, -motility, -feeding and eventually death. Tissue wasting is found to be mediated by autophagy and results in host mobilization of amino acids and sugars into circulation. Natural abundance Carbon 13 tracing demonstrates that tumor biomass is increasingly derived from host tissues as a nutrient source as wasting progresses. We conclude that host autophagy mediates organ wasting and nutrient mobilization that is utilized for tumor growth.

cell biology↗