Welcome to the Dr. Lin Xu Lab.
My lab advances medical AI by developing large language models, virtual cells, and digital twins that integrate bulk, single-cell, and spatial multi-omics data, as well as imaging and Electronic Health Record (EHR) patient data, to uncover disease mechanisms, identify therapeutic targets, and guide precision medicine. Since establishing my laboratory at UT Southwestern in 2022, I had published 134 peer-reviewed articles, including 21 for which I am a corresponding author. As of August 2026, these research papers had received 5,489 citations and an h-index of 41. The lab’s research has been published in a series of high-impact journals, including Nature (2022, 2025), Science (2023, 2026), Cell (2024, 2026), Cancer Cell (2022, 2023), Nature Medicine, Elife, PNAS, Nature Machine Intelligence, Nature Immunology, Nature Metabolism, Nature Communications, Science Translational Medicine, Science Advance, Molecular Cell, Genes & Development, Cell Reports, Journal of Clinical Investigation, Circulation, Circulation Research, and Developmental Cell.
My lab has received support from federal agencies, state funds, and private foundations. I have served as PI or MPI on 12 NIH, CPRIT, and foundation grants with combined total costs exceeding $10 million, including PI/MPI role of three active NIH R01 awards and two NCI R21 awards. Since 2022, I have also served as a co-investigator on 16 NIH R01 awards funded by NIDDK, NICHD, NCI, NINDS, NHLBI, NHGRI, and NIAMS, as well as 11 other research grants from the U.S. Department of Defense, the Cancer Prevention and Research Institute of Texas (CPRIT), and private foundations. In recognition of my research in AI-enabled biomarker discovery and drug design, I was named a Hyundai Hope Scholar in 2024 and a Sam Day Foundation Scholar in 2025.
My trainees have earned competitive national awards and advanced to independent academic careers. Two of my co-mentored postdoctoral fellows have received NIH K99 Pathway to Independence Awards in 2024 and 2026, respectively. My graduate student also received a National Science Foundation Graduate Research Fellowship in 2023, and three of my postdoc and staff trainees was appointed as tenure-track Assistant Professors in the past five years.
Developing medical AI methods, including AI agents and large language models, to discover disease mechanisms
Develop machine learning and deep learning algorithms to study single-cell and spatial multi-omics data
Develop integrated multi-omics analysis to identify new biomarkers and therapeutic targets in human disease
Develop epigenomics-focused deep learning and bioinformatics algorithms
Abdullah KG, et al. (2026) Gliomas phenocopy an inborn error of metabolism to drive neuronal activity and tumor growth. Cell S0092-8674(26)01010-X. doi: 10.1016/j.cell.2026.08.037. PMID: 42743926
Sternisha AC, et al. (2026) A transcriptional biosensor reveals mechanisms of α-ketoglutarate signaling to chromatin. Science 393(6808):eadx8675.
Shi DD, et al. (2026) Vorasidenib improves response to subsequent chemoradiation in a genetically engineered mouse model of IDH-mutant glioma. Science Translational Medicine 18(861):eaee5876.
Wang S, .. Lin Xu* (co-corresponding Author), Xiao G*, Xie Y*. (2026) MicNet: integrating spatially resolved transcriptomes and pathology images by contrastive deep neural network. Genome Biology 27(1):263.
Jiang X, Guo Y, Guo L, Zhong L, Wang J, Xiao G, Li Q, Lin Xu* (co-corresponding Author) (2026) SpaFun: discovering domain-specific spatial expression patterns and new disease-relevant genes using functional principal component analysis. Briefings in Bioinformatics. 27(2):bbag150.
He Y, et al. (2026) Claudins interact with LILRB immune inhibitory receptors to promote myeloid immunosuppression in cancer. Science Immunology 11(118):eadt7832. Beachum AH, Xiao X, Zhou Y, Li Q, Xiao G, Lin Xu* (co-corresponding Author) (2026) Advances in predicting omics profiles from imaging data. Briefings in Bioinformatics. 27(2):bbag090.
Huang HC, et al (2026). Kras G12C- and G12D-driven lung cancers differ in oncogenic potency, immunogenicity, and relapse after Kras inhibition in mouse models. Science Translational Medicine 18(835):eadq6647.
Tang C, Zhou Y, Xiao X, Dong L, Yu L, Li Q, Xiao G, Lin Xu* (Corresponding Author). (2026) 3D reconstruction of spatial transcriptomics with spatial pattern enhanced graph convolutional neural network. Briefings in Bioinformatics. 27(1):bbag060.
Caravia XM, et al. (2025). Precise gene editing of pathogenic Lamin A mutations corrects cardiac disease. Proceedings of the National Academy of Sciences USA 122(43):e2515267122.
Gan P, et al. (2025) Engineering a serum response factor superactivator of smooth muscle gene expression with a condensate-forming domain. Proceedings of the National Academy of Sciences USA 122(38):e2514363122.
Yang X, et al. (2025). Secretogranin 2 binds LILRB4 resulting in immunosuppression. Nature Immunology 26(9):1567-1580.
Zhou J, et al. (2025). SWI/SNF ATPase silenced HLF potentiates lung metastasis in solid cancers. Nature Communications. 16(1):5226.
Lu Z, Lin Xu* (co-corresponding Author), Wang X#. BIT: Bayesian Identification of Transcriptional regulators from epigenomics-based query region sets. Nature Communications. 16(1):4966.
Liao C, et al (2025). BBOX1 restrains TBK1-mTORC1 oncogenic signaling in clear cell renal cell carcinoma. Nature Communications. 16(1):1543.
Chen S, et al (2025). PGLYRP-1 mediated intracellular peptidoglycan detection promotes mucosal protection. Nature Communications. 16(1):1864.
Zhou Y, Xiao X, Dong L, Tang C, Xiao G#, Lin Xu* (co-corresponding Author), (2025) Cooperative integration of spatially resolved multi-omics data with COSMOS. Nature Communications. 1616(1):27.
IGVF Consortium (2024). Deciphering the impact of genomic variation on function. Nature 633(8028):47-57.
Lu Z, Xiao X, Zheng Q, Wang X*, Lin Xu* (Corresponding Author). (2024) Assessing next-generation sequencing-based computational methods for predicting transcriptional regulators with query gene sets. Briefings in Bioinformatics. 2024 Jul 25;25(5):bbae366. (impact factor 13.9)
Jiang X. …Lin Xu*, Guanghua Xiao*, Qiwei Li* (Corresponding Author). (2024) iIMPACT: integrating image and molecular profiles for spatial transcriptomics analysis. Genome Biology 25 (1), 1-25 (impact factor 12.3)
Venkateswaran N, et al. (2024) Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis. Nature Communications. 15(1):4266. doi: 10.1038/s41467-024-47868-3.
Lin CC. et al. (2024) PRMT5 is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer. Nature Communications 15 (1), 2287
Eglenen-Polat B. et al. (2024) A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer. Nature Communications 15 (1), 672
Tiburcio PDB, …Lin Xu*, Chen KS * (Corresponding Author). (2024) DROSHA Regulates Mesenchymal Gene Expression in Wilms Tumor. Xu L, Chen KS. Molecular Cancer Research 2024 Aug 2;22(8):711-720. (impact factor 6.3)
Vishlaghi N, et al. (2024) Vegfc-expressing cells form heterotopic bone after musculoskeletal injury. Cell Reports. 43(4):114049.
Gan P. et al (2024) Coactivator condensation drives cardiovascular cell lineage specification. Science Advances 10(11):eadk7160.
Hu L. et al. (2024) Kinome-wide siRNA screen identifies a DCLK2-TBK1 oncogenic signaling axis in clear cell renal cell carcinoma. Molecular Cell 84 (4), 776-790. e5
Hernandez KC. et al. (2024) CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway. Proceedings of the National Academy of Sciences USA 121 (4), e2315925121
Lebek S. et al. (2024) CRISPR-Cas9 base editing of pathogenic CaMKIIδ improves cardiac function in a humanized mouse model. The Journal of Clinical Investigation 134 (1)
Wei Y. et al. (2023) Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture. Cell 186 (26), 5859-5875. e24
He F. et al. (2023) Genomic profiling of subcutaneous patient-derived xenografts reveals immune constraints on tumor evolution in childhood solid cancer. Nature Communications 14 (1), 7600
Lin Xu* (Corresponding Author). et al. (2023) Integrated genomic analysis reveals aberrations in WNT signaling in germ cell tumors of childhood and adolescence. Nature Communications 14 (1), 2636
Rogojina A. …Peter J Houghton*, Lin Xu* (Corresponding Author). (2023) Comprehensive characterization of patient-derived xenograft models of pediatric leukemia. IScience 26 (11)
Zhu M. et al. (2023) Loss of p53 and mutational heterogeneity drives immune resistance in an autochthonous mouse lung cancer model with high tumor mutational burden. Cancer Cell 41 (10), 1731-1748. e8
Yu L. et al. (2023) Macrophage-to-endothelial cell crosstalk by the cholesterol metabolite 27HC promotes atherosclerosis in male mice. Nature Communications 14 (1), 4101
Dos Santos et al. (2023) Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution. Nature Communications 14 (1), 4333
Li Y, et al. (2023) Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation. Nature Communications 14 (1), 2610
Lee S. et al. (2023) Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice. Nature Cardiovascular Research 2 (5), 438-448.
Shah AM. et al. (2023) TWIST2-mediated chromatin remodeling promotes fusion-negative rhabdomyosarcoma. Science Advances 9 (17), eade8184
Chai AC. et al. (2023) Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice. Nature Medicine 29 (2), 401-411
Watson S. et al. (2023) VGLL2-NCOA2 leverages developmental programs for pediatric sarcomagenesis. Cell Reports 42 (1)
Lebek S. et al. (2023) Ablation of CaMKIIδ oxidation by CRISPR-Cas9 base editing as a therapy for cardiac disease. Science 379 (6628), 179-185
Nishiyama T. et al. (2022) Precise genomic editing of pathogenic mutations in RBM20 rescues dilated cardiomyopathy. Science Translational Medicine 14 (672), eade1633
Shi DD, et al. De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma. Cancer Cell. 2022 Aug 12; doi: 10.1016/j.ccell.2022.07.011.
Zhang Q, et al. Distinct functional properties of murine perinatal and adult adipose progenitor subpopulations. Nature Metabolism 2022 Aug 18; doi: 10.1038/s42255-022-00613-w.