Biology subjects

Pandell, N.

Publications and source records attributed to Pandell, N..

3 recordsLinked to original sources

bioRxiv2026

X-CODE: a dual RNA barcoding system for multi-platform clonal tracking and spatial phenotyping

Experimental dissection of clonal dynamics in complex tissues requires barcoding systems that are scalable, compatible with different analytical platforms, providing phenotypic and spatial resolution. Here we introduce X-CODE, a dual-expressed RNA barcoding system designed to enable high-complexity clonal tracking across sequencing-based, cytometric, and spatial imaging modalities within a unified experimental framework. X-CODE combines a combinatorial, probe-detectable long RNA barcode with a matched short sequencing barcode, enabling seamless integration of probe-based readouts with sequencing and barcode-guided clonal retrieval. We demonstrate robust X-CODE detection by mass cytometry and imaging-based platforms, including spatial RNA barcode readout using via a repurposed Akoya PhenoCycler-Fusion protocol. In addition, we show compatibility with MALDI mass spectrometry imaging for co-registration of clonal and metabolic information. We further demonstrate the feasibility of X-CODE detection within probe-based spatial transcriptomics using the 10x Genomics Xenium platform. Applied to an in vivo model of androgen deprivation in prostate cancer, X-CODE reveals clonal architecture, selection and clone-specific phenotypic and metabolic plasticity underlying castration resistance. Together, X-CODE provides a flexible and broadly accessible platform for integrated clonal analysis across spatial, phenotypic, and molecular dimensions.

cancer biology↗

bioRxiv2025

ProMPt: A modular preclinical platform for functional modelling of prostate cancer heterogeneity and therapeutic vulnerabilities

Prostate cancer progression is driven by heterogenous genetic, phenotypic, and microenvironmental programs that remain challenging to model experimentally. Existing systems such as genetically engineered mouse models, xenografts, and patient-derived organoids have each advanced mechanistic insight but are limited by genetic scope, scalability, or lack of immune context. To overcome these constraints we developed ProMPt, a genetically-defined syngeneic mouse modelling platform that captures combinations of the most recurrent clinical prostate cancer genomic alterations to enable scalable in vitro and in vivo interrogation of prostate cancer evolution. Tumours derived from ProMPt organoids recapitulate the histologic and molecular diversity of human disease. Cross - species transcriptomic integration and multivariate single-cell analysis under defined culture permutations revealed conserved phenoscapes, highlighting a central role for MYC in disease progression and therapy resistance. Guided by these insights, preclinical intervention studies demonstrated that combined MAPK inhibition and blockade of protein translation synergistically suppressed tumour growth in castration-resistant models. This combination not only suppressed proliferation but also remodelled the tumour immune landscape, underscoring its dual epithelial and microenvironmental effects. Together, these findings establish ProMPt as a versatile framework for linking genotype, lineage plasticity, and therapeutic vulnerability in prostate cancer.

cancer biology↗

bioRxiv2019

Pancreatic tumor organoids for modeling in vivo drug response and discovering clinically-actionable biomarkers

Patient-derived models are transforming translational cancer research. It is not clear if the emergence of patient-derived organoid (PDO) models can extend the utility of the widely used patient-derived xenograft (PDX). In addition, the utility of PDO models for serum biomarker discovery is not known. Here, we demonstrate that PDO models recapitulate the genomics, cell biology, glycomics and drug responses observed in PDX models. Furthermore, we demonstrate the applicability of PDO models for identification of N-glycans that are enriched in the glycome of pancreatic ductal adenocarcinoma (PDAC). Surprisingly, among all the glycans observed in PDX and PDOs, a core set of 57 N-glycans represent 50-94% of the relative abundance of all N-glycans detected, suggesting that only a subset of glycans dominate the cell surface landscape in PDAC. In addition, we outline a tumor organoid-based pipeline to identify surface proteins in extracellular vesicles (EV) from media supernatant of PDO cultures. When combined with the affinity-based validation platform, the EV surface proteins discovered in PDOs are effective in differentiating patients with PDAC from those with benign pancreatitis in the clinic, identifying PDO as powerful discovery platform for serum biomarkers. Thus, PDOs extend the utility of the archival collections of PDX models for translational research and function as a powerful platform for identification of clinically-actionable biomarkers in patients blood. Significance statementTumor organoids extend the utility of PDX models as platforms for investigating drug response, glycosylation changes and function as new platforms for discovering blood-based biomarkers

cancer biology↗