Biology subjects

Mohammad, I. A.

Publications and source records attributed to Mohammad, I. A..

3 recordsLinked to original sources

bioRxiv2025

LabOS: The AI Co-Scientist That Sees and Works With Humans

Modern science advances fastest when thought meets action. LabOS represents the first AI co-scientist that unites computational reasoning with physical experimentation through multimodal perception, self-evolving agents, and XR-enabled, embodied human-AI collaboration. To empower agentic AI with embodied intelligence, we built LabSuperVision, the first vision-language-model (VLM) benchmark spanning biomedical and materials science laboratories, designed to evaluate scientific perception and reasoning. This endowed LabOS with visual reasoning capabilities that surpass those of general-purpose models on laboratory-specific tasks. By connecting multi-model AI agents, smart glasses, and human-AI-robot collaboration, LabOS allows AI to see what scientists see, understand experimental context, and participate in real-time execution through immersive XR interaction and robotic autonomation. Across applications-from cancer immunotherapy target discovery to cell engineering-LabOS shows that AI can move beyond computational design to participation, turning the laboratory into an intelligent, collaborative environment where human and machine discovery evolve together.

bioengineering↗

bioRxiv2025

Surfaceome CRISPR activation screening uncovers ligands regulating tumor sensitivity to NK cell killing

Natural killer (NK) cell-based immunotherapies represent a promising avenue for cancer treatment due to their ability to eliminate cancer cells independently of antigen presentation and potential for "off-the-shelf" use. However, the molecular determinants governing tumor cell susceptibility to NK cell-mediated cytotoxicity remain incompletely understood. Here we employed CRISPR activation (CRISPRa) screening to systematically identify cancer cell surface regulators of NK cell killing across multiple cancer types. Using a comprehensive surfaceome-focused library, we screened human and murine cancer cell lines co-cultured with NK cells, identifying both known and novel ligands that modulate NK cell cytotoxicity. Our screens revealed established factors including CD43 (encoded by SPN), while uncovering previously uncharacterized regulators such as CD44, PDPN, and Siglec-1/CD169. Validation through complementary cDNA overexpression and genetic knockout approaches confirmed that disruption of CD43, CD44, PDPN, and Siglec-1 significantly altered cancer cell susceptibility to NK killing both in vitro and in humanized mouse models. Analysis of clinical datasets show that expression of identified factors correlates with patient survival outcomes in an NK-context dependent manner supporting their therapeutic relevance. Most notably, our mechanistic studies demonstrate that CD43-mediated NK cell resistance operates independently of its previously proposed interaction with Siglec-7 on NK cells. Furthermore, we find that targeting CD43 on either NK cells or engineered T cells substantially enhances their cytotoxic activity against leukemia cell lines. These results establish gain-of-function screening as a powerful approach for discovering immunoregulatory surface proteins and identify multiple promising targets for enhancing NK cell-based cancer immunotherapies.

immunology↗

bioRxiv2025

ACTL6A regulates the Warburg effect through coordinated activation of AP-1 signaling in head and neck squamous cell carcinoma

ACTL6a is an essential component of SWI/SNF and expressed on the chromosome 3q26 cytoband, which is amplified in head and neck squamous cell carcinomas (HNSCC). While ACTL6A is emerging as an oncogene, its role as a treatment target and mechanisms of transcription factor induction remain unknown. Here, we show that ACTL6A expression is a mediator of the Warburg effect, with ACTL6A knockdown inducing mitochondrial dependency and significantly decreasing levels of aerobic glycolysis. These effects lead to near complete attenuation of hypoxic cell growth by blunting induction of HIF1 and HIF2 protein expression. They also sensitize treatment resistant HNSCC cells to the tumor killing effects of the complex I inhibitor IACS-010759 in vivo. Using ATAC-seq, we identify ACTL6A as a mediator of chromatin accessibility of AP-1 transcription factor sites and find that it regulates upstream MAPK signaling through induction of Ras and Galectin-1. These effects sensitize ACTL6A over-expressing cells to inhibition of glycolysis by MEK inhibitors. Our results link SWI/SNF subunit amplification with potentiation of MAPK signaling in HNSCC and provide a novel mechanism by which cancer cells drive aerobic glycolysis and reduce mitochondrial dependency. We leverage these findings to propose treatment strategies for hypoxic tumors with SWI/SNF subunit amplifications.

cancer biology↗