Biology subjects

Maqsood, A.

Publications and source records attributed to Maqsood, A..

3 recordsLinked to original sources

bioRxiv2025

Aberrant NOTUM+ Program Induced in LGR5+ Crypt Base Columnar Cells Maintains an Immunosuppressive Niche in Colorectal Cancer

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with treatment failure largely driven by cancer stem-like cells that resist conventional chemoradiation and subsequently initiate tumor recurrence. While immune checkpoint blockade is effective in microsatellite instability-high (MSI-H) CRCs, the majority of CRCs are microsatellite stable (MSS) and exhibit immune exclusion, rendering them refractory to immunotherapy. Here, we identify a previously uncharacterized cancer cell subtype, which we term cancerous Crypt Base Columnar (canCBC) cells. These cells transcriptionally resemble normal LGR5+ CBC cells but activate an aberrant WNT/{beta}-catenin signalling inhibitory program, marked by NOTUM expression. We show that canCBC cells are specifically enriched in MSS tumors, where their presence correlates with reduced CD8 T cell infiltration, broader immune exclusion, and a propensity for regional lymphatic dissemination. Consistently, targeted ablation of canCBCs enhances the tumor-clearing potential of CD8 T cells. This study identifies a novel therapeutic target for overcoming immune exclusion and improving immunotherapy responses in MSS CRCs.

cancer biology↗

bioRxiv2024

A Functional Map of the Human Intrinsically Disordered Proteome

Intrinsically disordered regions (IDRs) represent at least one-third of the human proteome and defy the established structure-function paradigm. Because IDRs often have limited positional sequence conservation, the functional classification of IDRs using standard bioinformatics is generally not possible. Here, we show that evolutionarily conserved molecular features of the intrinsically disordered human proteome (IDR-ome), termed evolutionary signatures, enable classification and prediction of IDR functions. Hierarchical clustering of the human IDR-ome based on evolutionary signatures reveals strong enrichments for frequently studied functions of IDRs in transcription and RNA processing, as well as diverse, rarely studied functions, ranging from sub-cellular localization and biomolecular condensates to cellular signaling, transmembrane transport, and the constitution of the cytoskeleton. We exploit the information that is encoded within evolutionary conservation of molecular features to propose functional annotations for every IDR in the human proteome, inspect the conserved molecular features that correlate with different functions, and discover frequently co-occurring IDR functions on the proteome scale. Further, we identify patterns of evolutionary conserved molecular features of IDRs within proteins of unknown function and disease-risk genes for conditions such as cancer and developmental disorders. Our map of the human IDR-ome should be a valuable resource that aids in the discovery of new IDR biology.

bioinformatics↗

bioRxiv2023

Lights, Camera, Mirrors, Action! Toolbox for 3D Reconstruction and Analysis Using a Single Camera and Planar Mirrors

The advent of high-speed cameras being made available for commercial use has facilitated the discovery of intriguing animal behaviors. However, analyzing animal kinematics in three dimensions necessitates using several high-speed cameras, which are specialized equipment and come at a significant expense. In this study, we utilize a conventional methodology of capturing synchronized multiple views using a solitary camera and planar mirrors. We introduce a user-friendly software package that facilitates the calibration of this economical setup and enables the three-dimensional (3D) analysis of high-rate maneuvers. Within[~] 15 minutes, a single high-speed camera is calibrated and can be used to acquire 3D data. We accompany the toolbox with a detailed user guide and video tutorial (https://tinyurl.com/yckm9y6b) for ease of use. We accurately reconstruct the wing beats of multiple flies (dragonfly, butterfly).

animal behavior and cognition↗