Sheng Li

Dr. Sheng Li’s lab develops AI-driven multi-omics approaches to investigate how aging and somatic mutations reshape hematopoietic stem cells, driving clonal hematopoiesis and leukemia.By integrating single-cell, spatial, and long-read sequencing, we uncover how epigenetic and transcriptional programs influence stem-cell aging and cancer evolution.Our interdisciplinary team combines computational biology and translational genomics to transform large-scale data into actionable insights that advance precision medicine and improve human health.

• Leukemia & Lymphoma Society: Career Development Program Scholar Award, 2024-2029
• American Association for Cancer Research: NextGen Star, 2020-2021
• National Institute of General Medical Sciences: Maximizing Investigators’ Research Award, 2019-2024
• Leukemia Research Foundation: New Investigator Award, 2017-2018

• Advancing biological understanding of cellular senescence with computational multiomics. Nat Genet. 2025 Oct; 57(10):2381-2394.. View in PubMed
• NANOME: A Nextflow pipeline for haplotype-aware allele-specific consensus DNA methylation detection by nanopore long-read sequencing. bioRxiv. 2025 Jul 04.. View in PubMed
• Inferring single-cell spatial gene expression with tissue morphology via explainable deep learning. bioRxiv. 2025 Jun 02.. View in PubMed
• MorPhiC Consortium: towards functional characterization of all human genes. Nature. 2025 Feb; 638(8050):351-359.. View in PubMed
• Deciphering Aging, Genetic, and Epigenetic Heterogeneity in Cancer Evolution: Toward Personalized Precision Preventative Medicine. Aging and Cancer. 2025; 6(1):19-29.
• Quantifying interpretation reproducibility in Vision Transformer models with TAVAC. Sci Adv. 2024 12 20; 10(51):eabg0264.. View in PubMed
• Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function. Cell Metab. 2024 Aug 06; 36(8):1795-1805.e6.. View in PubMed
• Causal network perturbation analysis identifies known and novel type-2 diabetes driver genes. bioRxiv. 2024 May 26.. View in PubMed
• Data-driven modeling of core gene regulatory network underlying leukemogenesis in IDH mutant AML. NPJ Syst Biol Appl. 2024 Apr 09; 10(1):38.. View in PubMed
• Challenges and opportunities for modeling aging and cancer. Cancer Cell. 2023 04 10; 41(4):641-645.. View in PubMed
• Inferring the Cancer Cellular Epigenome Heterogeneity via DNA Methylation Patterns. Cancer Treat Res. 2023; 190:375-393.. View in PubMed
• NetAct: a computational platform to construct core transcription factor regulatory networks using gene activity. Genome Biol. 2022 12 27; 23(1):270.. View in PubMed
• Interchromosomal interaction of homologous Stat92E alleles regulates transcriptional switch during stem-cell differentiation. Nat Commun. 2022 07 09; 13(1):3981.. View in PubMed
• DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation. Genome Biol. 2021 10 18; 22(1):295.. View in PubMed
• Network Topology of Biological Aging and Geroscience-Guided Approaches to COVID-19. Front Aging. 2021 Jul; 2.. View in PubMed
• epihet for intra-tumoral epigenetic heterogeneity analysis and visualization. Sci Rep. 2021 01 11; 11(1):376.. View in PubMed
• Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development. Cell Rep. 2020 12 08; 33(10):108448.. View in PubMed
• Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML. Cancer Discov. 2020 12; 10(12):1934-1949.. View in PubMed
• CUP-AI-Dx: A tool for inferring cancer tissue of origin and molecular subtype using RNA gene-expression data and artificial intelligence. EBioMedicine. 2020 Nov; 61:103030.. View in PubMed
• Lung mesenchymal cells elicit lipid storage in neutrophils that fuel breast cancer lung metastasis. Nat Immunol. 2020 11; 21(11):1444-1455.. View in PubMed
• HBA-DEALS: accurate and simultaneous identification of differential expression and splicing using hierarchical Bayesian analysis. Genome Biol. 2020 07 13; 21(1):171.. View in PubMed
• ChIA-PIPE: A fully automated pipeline for comprehensive ChIA-PET data analysis and visualization. Sci Adv. 2020 07; 6(28):eaay2078.. View in PubMed
• CRISPR artificial splicing factors. Nat Commun. 2020 06 12; 11(1):2973.. View in PubMed
• TET2 deficiency reprograms the germinal center B cell epigenome and silences genes linked to lymphomagenesis. Sci Adv. 2020 06; 6(25):eaay5872.. View in PubMed
• Loss of CHD1 Promotes Heterogeneous Mechanisms of Resistance to AR-Targeted Therapy via Chromatin Dysregulation. Cancer Cell. 2020 04 13; 37(4):584-598.e11.. View in PubMed
• Graph embedding and unsupervised learning predict genomic sub-compartments from HiC chromatin interaction data. Nat Commun. 2020 03 03; 11(1):1173.. View in PubMed
• Molecular Biology and Evolution of Cancer: From Discovery to Action. Mol Biol Evol. 2020 02 01; 37(2):320-326.. View in PubMed
• The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing. Nat Cancer. 2020; 1:653-664.. View in PubMed
• Enhanced CRISPR-based DNA demethylation by Casilio-ME-mediated RNA-guided coupling of methylcytosine oxidation and DNA repair pathways. Nat Commun. 2019 Sep 20; 10(1):4296.. View in PubMed
• Ontogeny and Biology of Human Small Airway Epithelial Club Cells. Am J Respir Crit Care Med. 2018 12 01; 198(11):1375-1388.. View in PubMed
• TET2 Deficiency Causes Germinal Center Hyperplasia, Impairs Plasma Cell Differentiation, and Promotes B-cell Lymphomagenesis. Cancer Discov. 2018 12; 8(12):1632-1653.. View in PubMed
• Extracellular vesicles in DLBCL provide abundant clues to aberrant transcriptional programming and genomic alterations. Blood. 2018 08 16; 132(7):e13-e23.. View in PubMed
• Jak1 Integrates Cytokine Sensing to Regulate Hematopoietic Stem Cell Function and Stress Hematopoiesis. Cell Stem Cell. 2017 10 05; 21(4):489-501.e7.. View in PubMed
• Genetic and epigenetic heterogeneity and the impact on cancer relapse. Exp Hematol. 2017 10; 54:26-30.. View in PubMed
• Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nat Med. 2016 07; 22(7):792-9.. View in PubMed
• A benchmark for RNA-seq quantification pipelines. Genome Biol. 2016 Apr 23; 17:74.. View in PubMed
• Genetic and epigenetic heterogeneity in acute myeloid leukemia. Curr Opin Genet Dev. 2016 02; 36:100-6.. View in PubMed
• Clinical Genomics: Challenges and Opportunities. Crit Rev Eukaryot Gene Expr. 2016; 26(2):97-113.. View in PubMed
• Correction: Tissue elasticity regulated tumor gene expression: implication for diagnostic biomarkers of primitive neuroectodermal tumor. PLoS One. 2015; 10(5):e0128504.. View in PubMed
• Dynamic evolution of clonal epialleles revealed by methclone. Genome Biol. 2014 Sep 27; 15(9):472.. View in PubMed
• Assessing technical performance in differential gene expression experiments with external spike-in RNA control ratio mixtures. Nat Commun. 2014 Sep 25; 5:5125.. View in PubMed
• Multi-platform assessment of transcriptome profiling using RNA-seq in the ABRF next-generation sequencing study. Nat Biotechnol. 2014 Sep; 32(9):915-925.. View in PubMed
• Detecting and correcting systematic variation in large-scale RNA sequencing data. Nat Biotechnol. 2014 Sep; 32(9):888-95.. View in PubMed
• The pivotal regulatory landscape of RNA modifications. Annu Rev Genomics Hum Genet. 2014; 15:127-50.. View in PubMed
• Identification of kinase fusion oncogenes in post-Chernobyl radiation-induced thyroid cancers. J Clin Invest. 2013 Nov; 123(11):4935-44.. View in PubMed
• Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia. Nat Genet. 2013 Mar; 45(3):290-4.. View in PubMed
• Mandarin fish caveolin 1 interaction with major capsid protein of infectious spleen and kidney necrosis virus and its role in early stages of infection. J Virol. 2013 Mar; 87(6):3027-38.. View in PubMed
• An optimized algorithm for detecting and annotating regional differential methylation. BMC Bioinformatics. 2013; 14 Suppl 5:S10.. View in PubMed
• methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biol. 2012 Oct 03; 13(10):R87.. View in PubMed
• Tyrosine phosphorylation modulates store-operated calcium entry in cultured rat epididymal basal cells. J Cell Physiol. 2011 Apr; 226(4):1069-73.. View in PubMed
• Sodium coupled bicarbonate influx regulates intracellular and apical pH in cultured rat caput epididymal epithelium. PLoS One. 2011; 6(8):e22283.. View in PubMed
• Functional studies of acid transporter in cultured rat epididymal cell. Fertil Steril. 2010 May 15; 93(8):2744-9.. View in PubMed
• Stimulating effects of dopamine on chloride transport across the rat caudal epididymal epithelium in culture. Biol Reprod. 2009 Jan; 80(1):13-23.. View in PubMed
• Outreach clinic experiment extends care with paramedics. Hospitals. 1977 Jan 01; 51(1):77-80.. View in PubMed
• Delineation of the intimate details of the backbone conformation of pyridine nucleotide coenzymes in aqueous solution. Biochem Biophys Res Commun. 1975 Oct 27; 66(4):1173-9.. View in PubMed
• Digitoxin metabolism by rat liver microsomes. Biochem Pharmacol. 1975 Sep 01; 24(17):1639-41.. View in PubMed
• The amino acid sequence of Neurospora NADP-specific glutamate dehydrogenase. Peptic and chymotryptic peptides and the complete sequence. Biochem J. 1975 Sep; 149(3):757-73.. View in PubMed

• Alonzo, Todd
• Wiemels, Joseph
• Liang, Gangning
• Breton, Carrie
• Farnham, Peggy
• Alachkar, Houda
• Shibata, Darryl
• Siegmund, Kimberly
• Lenz, Heinz-Josef
• Peters, Anne