Cell

Identifying existing drugs that reverse disease-associated gene expression has been widely explored for drug repurposing, but can we identify entirely new drugs that can do this? ⁠ ⁠ Xing et al. developed a deep-learning-based drug discovery platform ("GPS"), guided by transcriptomic features, that screens large compound libraries and optimizes lead molecules. They developed a model that captures transcriptomic perturbation signatures solely from chemical structures, then deployed it on large libraries of compounds. By incorporating structure-gene-activity relationships, they can uncover drug mechanisms from transcriptomic data. GPS was demonstrated across multiple diseases. They uncovered several compounds relevant for hepatocellular carcinoma and idiopathic pulmonary fibrosis that were subsequently validated.⁠ ⁠ ⁠Read more by clicking on this image in our link in bio 👉 @cell_journal ⁠ ⁠⁠ 📷: Xing et al. "Deep-learning-based de novo discovery and design of therapeutics that reverse disease-associated transcriptional phenotypes"⁠ /cell/fulltext/S0092-8674(26)00223-0⁠ ⁠ #Cell #CellPress #science #research #⁠drug #pharma #therapeutics #AI #deeplearning #drugdiscovery⁠ ⁠

New issue alert! Featuring a Review on the biology and clinical progress of antibody-drug conjugates, as well as research articles on the multiomics profiles across ethinicity, geography and age, the targeting of uPAR for solid tumor therapy, and the resistance mechanisms undermining the efficacy of RAS-targeting molecular glues and how to bypass them. ⁠ ⁠ On the cover: In this issue of Cell, Scharping et al. demonstrate that exhausted tumor-infiltrating lymphocytes undergo a breakdown of proteostasis, characterized by the accumulation of unfolded proteins. Inspired by Yayoi Kusama's hypnotic, proliferating forms, the cover artwork evokes this process through sprawling, tendril-like weeds that represent unfolded proteins accumulating within cells in the tumor microenvironment. ⁠ ⁠ ⁠To read more from our new issue, click on this image in our link in bio 👉️@cell_journal ⁠ ⁠ 📷️ credit: Yun Hsuan Elena Lin, PhD.⁠ /cell/current⁠ ⁠ #Cell #CellPress #CoverArt #ScientificIllustration #JournalCover science research InstaScience ⁠

When an asteroid as big as Mount Everest struck Earth 66 million years ago, it wiped out all non-avian dinosaurs and roughly a third of life on the planet. This is how the plants survived. 🌱🌿 In new research from @cell_journal , scientists analyzed the genomes of 470 flowering plants and compared the data with 44 plant fossils to see which blocks of genes persisted in plants over time. They found that these consistent genes tended to originate during major periods of environmental upheaval—such as the Cretaceous–Paleogene asteroid mass extinction that killed off the dinosaurs—as a result of whole-genome duplications, natural phenomena that can give plants an additional set of chromosomes. These duplication events likely helped many plants survive several of the most extreme environmental shake-ups in Earth’s history and could help today's plants tolerate climate change. “Whole-genome duplication is often seen as an evolutionary dead end in stable environments,” says author Yves Van de Peer of @ugent . “But in harsh situations, it can provide unexpected advantages.” To learn more, check out our link in bio 👉 @cellpress Cell, Chen et al., “The rise of polyploids during environmental upheaval” #plants #KPgExtinction #GenomeDuplication #research

The latest on hantavirus from Cell.⁠ ⁠ As the world has learned from the recent hantavirus outbreak on a cruise ship, hantaviruses, specifically the strain known as the Andes virus, can cause frequently fatal hantavirus cardiopulmonary syndrome in humans, and human-to-human transmission through close contact has been documented. Despite the public health threat posed by the Andes virus, there are no approved vaccines or therapeutics.⁠ ⁠ Glycoproteins on the surface of hantavirus virions are the primary targets of neutralizing antibody therapeutics. Here, Guo et al. determined the high resolution (2.35 Å) structure of the Andes virus glycoprotein tetramer and its interactions with neutralizing antibody ADI-65534. These structures are important for designing effective vaccines and treatments for Andes virus and other hantaviruses.⁠ ⁠ 📹️ : Hinge motion of two Andes virus tetramers⁠ ⁠ Read more by clicking on this image in our link in bio 👉 @cell_journal ⁠ ⁠⁠ "High-resolution in situ structures of hantavirus glycoprotein tetramers"⁠ /cell/fulltext/S0092-8674(26)00117-0⁠ ⁠ #Cell #CellPress #science #research #hantavirus #andesvirus #structure #cryoem #virus

The entire cell cycle on a simulation 🖥️ ⁠ ⁠ A whole-cell spatial and kinetic model simulates the entire cell cycle of the minimal bacterium JCVI-syn3, including expression of all 493 genes, kinetics of the entire metabolic network, ribosome biogenesis, chromosome dynamics (including DNA replication), and morphological changes during growth and divisions. ⁠ ⁠ This quantitative characterization of cells as a function of time and space is expanding our understanding of the rules governing cellular life.⁠ ⁠ 📹️ : Cell cycle of a simulated cell - the visualization includes the Brownian dynamics chromosomes, lattice membrane, ribosomes, and transmembrane sugar transporter PtsG.⁠ ⁠ Read more by clicking on this image in our link in bio 👉 @cell_journal ⁠ ⁠⁠ "Bringing the genetically minimal cell to life on a computer in 4D"⁠ /cell/fulltext/S0092-8674(26)00174-1⁠ ⁠ #Cell #CellPress #science #research #modeling simulation wholecell virtual cell cellcycle

The making of nicotine⁠ ⁠ Nicotine, a psychoactive alkaloid, has played complex roles in human society for thousands of years due to its addictive potential. For plants, however, nicotine represents one of the most potent constitutive and inducible chemical defenses. ⁠ ⁠ The final enzymatic steps of nicotine biosynthesis have long remain elusive. Here Chang et al. complete the biosynthetic pathway. A 5-component metabolon assembles at vacuolar membranes to channel both nicotine biosynthesis and its transport. This integrated biosynthetic and transport machinery is transferable to heterologous systems for efficient nicotine production and pest resistance.⁠ ⁠ ⁠Read more by clicking on this image in our link in bio 👉 @cell_journal ⁠ ⁠⁠ 📷: Chang et al. ⁠ ⁠ Chang et al. "Complete biosynthesis of nicotine"⁠ /cell/fulltext/S0092-8674(26)00335-1⁠ ⁠ #Cell #CellPress #science #research #plants #nicotine #biosynthesis. #metabolism⁠ ⁠

PLANeT: Plant genomes towards a sustainable future 🧬🌴⁠ ⁠ Land plants underpin civilization and planetary health, yet their genomic diversity remains largely uncharted. ⁠ ⁠ This Perspective introduces the PLANeT initiative - an international effort of around 100 labs to generate high-quality, standardized genomes across the plant tree of life. Integrating artificial intelligence (AI) with genomics, PLANeT will decode conserved principles to advance fundamental plant biology, biodiversity conservation, crop improvement, and natural product discovery. ⁠ ⁠ ⁠Read more by clicking on this image in our link in bio 👉 @cell_journal ⁠ ⁠⁠ 📷: Depicts how phylogenomics and pangenomes can be combined to identify constrained, adaptive, and deleterious sites in the genomes as potential targets for molecular breeding (Wang et al. Figure 4 / Cell).⁠ ⁠ Wang et al. "PLANeT: Understanding and leveraging the genome of land plants for a sustainable future"⁠ /cell/fulltext/S0092-8674(26)00113-3⁠ ⁠ #Cell #CellPress #science #research #Review #Biodiversity #Plant #Genomics #Evolution #crops #sustainability⁠ ⁠

The UCLA ATLAS links genetic data to EHRs in a diverse biobank⁠ ⁠ Linking genetic data with electronic health records in hospital biobanks promises to advance precision medicine, but limited ancestral diversity constrains discovery and generalizability. ⁠ ⁠ Haas et al., analyzed 93,936 participants from the UCLA ATLAS Community Health Initiative to inform disease prevalence and genetic risk across five continental and 36 fine-scale ancestry groups. They discovered numerous unreported gene-phenotype associations. Polygenic scores (PGS) robustly predicted common diseases, with effects markedly diminished in non-Europeans. Furthermore, they reduced the pronounced European bias in curated clinical variants using computational predictors, uncovering unreported disease-gene associations. Longitudinal data revealed that semaglutide efficacy varies across ancestries, is associated with PGS for type 2 diabetes, and is modulated by genetic variation in PTPRU. These findings illustrate how ancestrally diverse biobanks from a single health system yield robust disease associations and pharmacogenomic insights.⁠ ⁠ ⁠⁠Read more by clicking on this image in our link in bio 👉 @cell_journal ⁠ ⁠⁠ 📷 Credit: Haas et al., Cell⁠ ⁠ "Advancing precision health discovery in a genetically diverse health system"⁠ /cell/fulltext/S0092-8674(26)00274-6⁠ ⁠ #Cell #CellPress #science #research #biobank #electronichealthrecord #polygenicscore #ancestry ⁠ ⁠

New issue alert 👉 cell.com/cell/current On the cover: Garg, Blume, et al. propose nutrigenomics to identify genetic diseases amenable to vitamin-based therapies. The approach nominates vitamin B3 as a therapy for NAXD deficiency. The cover depicts a tree bearing fruits that contain different vitamins branching from a trunk formed in the shape of DNA. It represents how our genes and nutrients intersect, resulting in the health of an organism. Image credit: Chiara Ricci-Tam Featured in the issue: PLANeT as a proposal for an international collaborative effort to generate high-quality, standardized genomes across the plant tree of life. PLANeT will engage around 100 labs to tackle pivotal questions for a sustainable future. /cell/fulltext/S0092-8674(26)00113-3 An anti-fibrotic drug selectively targeting vascular ROCK2 with potency in preclinical MASH models and clinical trials of human patients with liver fibrosis. /cell/fulltext/S0092-8674(26)00166-2 The complete biosynthesis pathway for nicotine and reconstitution of the metabolon in heterologous plant species with the aim of conferring pest resistance /cell/fulltext/S0092-8674(26)00335-1 Leveraging the UCLA ATLAS biobank to uncover ancestry-specific disease-gene links /cell/fulltext/S0092-8674(26)00274-6

Cell death in cancer 💀 Check out this new Review!⁠ ⁠ ⁠An ability to evade cell death is a hallmark of cancer cells. Restoring the body's ability to kill cancerous cells is an appealing anti-cancer strategy, but it requires a deep understanding of cell death programs. ⁠ ⁠ Cells can die via apoptosis, necroptosis, pyroptosis, ferroptosis, and other programs that we are just beginning to understand. This @cell_journal Review presents a unified framework for understanding the roles of major cell death programs in cancer development, progression, and treatment response, as well as addressing resistance to cancer cell death and immune suppression.⁠ ⁠ ⁠Read more by clicking on this image in our link in bio 👉 @cell_journal ⁠ ⁠⁠ 📷 Credit: Conrad et al. / Cell (Figure 4 and 6)⁠ ⁠ Conrad et al. "Cell death in cancer"⁠ /cell/fulltext/S0092-8674(26)00325-9⁠ ⁠ #Cell #CellPress #science #research #Review #Cancer #Tumor #celldeath #apoptosis #therapy #immunotherapy⁠ ⁠

Tumor angiogenesis and how to target it 🎯 ⁠ ⁠ Malignant cells recruit new blood vessels via angiogenesis to fuel tumor growth and progression. The abnormal structure and function of these vessels, resulting from an imbalance between pro- and anti-angiogenic signaling as well as from the physical forces, impair the delivery and efficacy of therapeutics. ⁠ ⁠ This @cell_journal Review synthesizes the evolving narrative of targeting angiogenesis from starving tumors to vascular normalization as a therapeutic principle and highlight recent spatial-omics revelations and the emerging role of neural, microbial, hormonal, and chronological factors. The authors elaborate on the molecular mechanisms of tumor vessel formation, how dysfunctional vessels cause an abnormal tumor microenvironmen and how vascular normalization enhances the delivery and efficacy of various therapies, including immunotherapies.⁠ ⁠ ⁠Read more by clicking on this image in our link in bio 👉 @cell_journal ⁠ ⁠⁠ 📷 Credit: Subudhi et al. / Cell (Figure 4)⁠ ⁠ Subudhi et al. "Targeting angiogenesis: Lessons from 25 years of normalizing tumor vasculature"⁠ /cell/fulltext/S0092-8674(26)00283-7⁠ ⁠ #Cell #CellPress #science #research #Review #Cancer #Tumor #Angiogenesis #vasculature #therapy #immunotherapy⁠ ⁠

Rising early-onset cancers challenge existing frameworks for understanding and managing cancer. ⁠ ⁠ Cancer in younger adults is rising globally and this epidemiological shift underscores the urgent need to accelerate the identification of novel causes and underlying biological networks, with the aim of translating these insights into prevention and interception strategies. ⁠ ⁠ This perspective outlines a roadmap for addressing this challenge by advancing the discovery of cancer causes, cancer risk assessment, and cancer preventability characterization. Shi et al., advocate for closer integration of epidemiologic and mechanistic studies and propose three interconnected frameworks that extend current epidemiologic approaches: a tissue ecosystem-anchored framework for cancer cause discovery, a biological state-based framework for precision cancer risk assessment, and a dynamic framework to characterize cancer preventability. ⁠ ⁠ This roadmap aims to stimulate conceptual, resource, and methodological advances to accelerate cancer etiology research and prevention in the era of rising early-onset cancers.⁠ ⁠ ⁠⁠Read more by clicking on this image in our link in bio 👉 @cell_journal ⁠ ⁠⁠ 📷 Credit: Shi et al., Cell⁠ ⁠ "Accelerating discovery of cancer causes for prevention in the era of rising early-onset cancers"⁠ /cell/fulltext/S0092-8674(26)00286-2⁠ ⁠ #Cell #CellPress #science #research #cancer #cancercauses #early-onsetcancer #epidemiology⁠ ⁠