Biology subjects

Dinesh, R. K.

Publications and source records attributed to Dinesh, R. K..

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↗

bioRxiv2024

Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties

Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in homeostatic conditions, but the underlying mechanisms of cancer stem cell niche development are unclear. Here we report that Dickkopf-2 (DKK2) is essential for the generation of cancer cells with Paneth cell properties during colon cancer metastasis. Splenic injection of Dkk2-knockout (KO) cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases. Transcriptome analysis showed reduction of Paneth cell markers such as lysozymes in KO organoids. Single cell RNA sequencing analyses of murine metastasized colon cancer cells and patient samples identified the presence of lysozyme positive cells with Paneth cell properties including enhanced glycolysis. Further analyses of transcriptome and chromatin accessibility suggested Hepatocyte nuclear factor 4-alpha (HNF4A) as a downstream target of DKK2. Chromatin immunoprecipitation followed by sequencing analysis revealed that HNF4A binds to the promoter region of Sox9, a well-known transcription factor for Paneth cell differentiation. In the liver metastatic foci, DKK2 knockout rescued HNF4A protein levels followed by reduction of lysozyme positive cancer cells. Taken together, DKK2-mediated reduction of HNF4A protein promotes the generation of lysozyme positive cancer cells with Paneth cell properties in the metastasized colon cancers.

cancer biology↗