About

Mingyao Li, Ph.D., is a Professor of Biostatistics in the Department of Biostatistics and Epidemiology at the University of Pennsylvania Perelman School of Medicine. She is also a Senior Scholar at the Center for Clinical Epidemiology and Biostatistics, Director of Biostatistics in the Gene Therapy Program, and Director of the Statistical Center for Single-Cell and Spatial Genomics. Her main research area is statistical genetics and genomics, with a focus on using statistical and machine learning approaches to understand cellular heterogeneity in human disease-relevant tissues, characterizing gene expression diversity across cell types, and studying cell state transitions and crosstalk using single-cell transcriptomics data. Dr. Li collaborates with researchers to identify complex disease susceptibility genes, contributing to studies on cardiometabolic diseases, age-related macular degeneration, Alzheimer's disease, chronic kidney disease, type 1 diabetes, and cancer. Her work aims to facilitate cell-specific functional studies, in vivo modeling, and the development of precision therapeutic strategies. She actively serves the scientific community as an Associate Editor of Statistics in Biosciences and has participated in NIH review committees.

Research topics

• Medicine
• Biology
• Genetics
• Computational biology
• Pathology
• Cell biology
• Internal medicine
• Cancer research

Selected publications

• Perk Is Dispensable for Smooth Muscle Cell Phenotype Switching in Atherosclerosis

  Arteriosclerosis Thrombosis and Vascular Biology · 2026-05-14

  article

  BACKGROUND: Smooth muscle cell (SMC) derived cells form the bulk of cells in atherosclerotic lesions and modulate lesion stability and cardiovascular disease outcomes. Unfolded protein response (UPR) markers, thin fibrous caps, and inflammation correlate with human lesion instability and rupture. In mice, UPR drives macrophage and endothelial apoptosis and inflammation, but its impact on lesion stability through SMC modulation is debated. The UPR protein Perk (protein kinase RNA-like ER kinase) was recently shown to drive SMC modulation in vivo, suggesting that depletion of SMC Perk may regulate lesion stability. METHODS: hypercholesterolemic mice. Lesions were scored for features of lesion stability and analyzed for differential expression at the single-cell level. Perk knockdown in primary murine SMCs was used to study Perk's effect on SMC modulation in vitro. UPR marker expression in human carotid lesions was assessed for UPR markers through scRNA-seq, bulk RNA-seq, and Xenium spatial transcriptomics. RESULTS: SMC Perk deletion in adult atherogenic mice did not affect weight gain or serum cholesterol levels. Lesions from Perk knockout mice resembled Perk WT counterparts with similar progression, lesion stability features, and cell populations. Scoring of UPR activity and differential expression analysis found little UPR activity in SMC and smooth muscle-derived cell populations. Perk was not required for in vitro SMC modulation in atherogenic conditions. No correlation was found between UPR markers and lesion stability or symptomatic clinical presentation in human carotid lesions, and UPR markers were expressed primarily in infiltrating leukocytes rather than in SMCs and stromal cells. CONCLUSIONS: SMC Perk UPR does not play a significant role in atherosclerotic SMC modulation, disease progression, or features of lesion stability in mice. Similarly, expression of markers of the Perk UPR pathway in humans does not correlate with human carotid lesion stability or clinical presentation.

  PublisherDOI

• High-resolution H&E images from the HistoSweep study across multiple tissues and diseases

  Zenodo (CERN European Organization for Nuclear Research) · 2026-01-05

  datasetOpen access

  his dataset contains eight high-resolution hematoxylin and eosin (H&E) stained tissue images used in the study HistoSweep enables cellular-resolution tissue quality control for gigapixel images in digital pathology and spatial omics. The images have been pre-processed by scaling and padding to ensure consistency across samples and compatibility with digital pathology workflows. Contents Lung atypical adenomatous hyperplasia (AAH) (contributed by K. Human laboratory) Lung_AAH.zip Atherosclerosis (three samples, contributed by L. Maegdefessel laboratory): Three samples: post Xenium profiling, post CODEX profiling, multi-sample tissue post CODEX profiling Artery_Atherosclerosis.zip Lymph node from melanoma patient (contributed by A. Huang laboratory) LymphNode_Melanoma.zip Kidney with renal cell carcinoma (RCC) (contributed by A. Huang laboratory) Kidney_RCC.zip Kidney tissues processed with CosMx (contributed by K. Susztak laboratory): One image containing two normal samples One image containing a normal and a type 2 diabetes (T2D) sample Kidney_MultiSample_T2D.zip PurposeThese images provide a diverse set of gigapixel H&E slides spanning multiple tissue types and disease contexts. They serve as a resource for reproducing, validating, and extending the analyses performed with HistoSweep, as well as for general use in histopathology and spatial omics research.

  PublisherDOI

• High-resolution H&E images from the HistoSweep study across multiple tissues and diseases

  Zenodo (CERN European Organization for Nuclear Research) · 2026-01-06

  datasetOpen access

  This dataset contains eleven high-resolution hematoxylin and eosin (H&E) stained tissue images used in the study HistoSweep enables cellular-resolution tissue quality control for gigapixel images in digital pathology and spatial omics. The images have been pre-processed by scaling and padding to ensure consistency across samples and compatibility with digital pathology workflows. Contents Lung atypical adenomatous hyperplasia (AAH) and lung adenocarcinoma samples (contributed by H. Kadara laboratory): Lung_AAH.zip (1 H&E slide) Lung_AD.zip (3 H&E slides) Atherosclerosis (contributed by L. Maegdefessel laboratory): (1) Post Xenium profiling, (2) post CODEX profiling, (3) multi-sample tissue post CODEX profiling Artery_Atherosclerosis.zip (3 H&E slides) Lymph node from melanoma patient (contributed by A. Huang laboratory) LymphNode_Melanoma.zip (1 H&E slide) Kidney with renal cell carcinoma (RCC) (contributed by A. Huang laboratory) Kidney_RCC.zip (1 H&E slide) Kidney tissues processed with CosMx (contributed by K. Susztak laboratory): (1) One image containing two normal kidney samples, (2) One image containing a normal and a type 2 diabetes (T2D) kidney sample Kidney_MultiSample_T2D.zip (2 H&E slides) PurposeThese images provide a diverse set of gigapixel H&E slides spanning multiple tissue types and disease contexts. They serve as a resource for reproducing, validating, and extending the analyses performed with HistoSweep, as well as for general use in histopathology and spatial omics research.

  PublisherDOI

• Challenges and Pathways of Process-Oriented Assessment in High School English Teaching

  Education and Social Work · 2025-06-13

  articleOpen access1st authorCorresponding

  This paper examines the challenges and implementation strategies of pro-cess-oriented assessment (POA) in high school English teaching within ex-am-driven educational systems. Focusing on the Chinese context, it identifies key barriers including institutional constraints, teacher capacity gaps, and technological limitations, while proposing practical solutions such as hybrid assessment models, teacher training programs, and technology-enhanced feed-back systems. The study highlights the potential of POA to transform lan-guage education by balancing formative and summative evaluation, ultimately foster-ing holistic competency development.

  PublisherDOI

• Single cell spatial transcriptomics integration deciphers the morphological heterogeneity of atherosclerotic carotid arteries

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-16 · 4 citations

  preprintOpen access

  Abstract The process of arterial atherosclerosis is characterised by accumulation of lipids and fibrous material with accompanying inflammation. As plaques progress, they restrict blood flow and cause rupture, which results in life threatening organ ischemia and dysfunction. Although extensively studied, a clear understanding of plaque heterogeneity and mechanisms that trigger their destabilization remains elusive. Our study reveals the molecular microarchitecture of human carotid artery plaques, using bulk and single-cell RNA sequencing combined with single cell spatial transcriptomics, for which we present optimized cell segmentation algorithms. We identified distinct plaque morphologies linked to different cell type compositions, impacting early and advanced lesion formation, as well as destabilization. Spatial transcriptomics enabled us further to determine an inflammatory smooth muscle cell subtype, localize regions of neovascularization, and assign hotspots for macrophage activity within distinct cellular neighbourhoods across lesions. For different macrophage substates, we propose gradual and locally contained transdifferentiation of subluminal inflammatory HMOX1 + macrophages into a lipid-handling TREM2 + phenotype within border zones of the fibrous cap and necrotic core. Our findings provide insight into the complex heterogeneity of human atherosclerosis by unravelling location and proximity of different mural and immune cell substates involved in plaque progression and vulnerability.

  PublisherOA PDFDOI

• Correction: The 3D Revolution in Cancer Discovery

  Cancer Discovery · 2025-01-13

  erratumOpen access
  PublisherOA PDFDOI

• Corrective Feedback in High School EFL Writing: Challenges and Solutions

  International Journal of Educational Development · 2025-06-26

  articleOpen access1st authorCorresponding

  This paper examines the challenges and solutions of implementing corrective feedback (CF) in high school English as a Foreign Language (EFL) writing in-struction. Despite CF’ s recognized role in improving linguistic accuracy, its ef-fectiveness is hindered by practical constraints. Key challenges include in-con-sistent student engagement, lack of consensus on optimal strategies, and insuf-ficient teacher training. Proposed solutions encompass differentiated feedback approaches, technology-enhanced systems, process-oriented writing instruc-tion, and student feedback literacy development. The paper concludes that a balanced, adaptive implementation of CF—supported by institutional re-forms and teacher collaboration—can transform it into a powerful tool for writing development in EFL classrooms.

  PublisherDOI

• Abstract 763: Multimodal spatial-omics atlas of lung premalignancy and adenocarcinoma reveals tumor initiating interplay between alveolar progenitors and inflammation

  Cancer Research · 2025-04-21

  article

  Abstract Background: The events mediating the transition of normal-appearing tissue (NAT) to adenomatous premalignant lesions (aPMLs) and minimally or locally invasive lung adenocarcinoma (LUAD) are very poorly narrated. Methods: We analyzed matching NATs, aPMLs, and LUADs from 25 patients using integrative approaches including spatial transcriptomics (ST, n=56 tissues), single-cell RNA-sequencing of fixed cells (scFFPE-seq) from matched uninvolved NAT, aPMLs and LUADs (n = 75 tissues), and whole exome sequencing (WES, n=79). A subset of tissues was also analyzed by sequential immunofluorescence (seqIF, COMET) and subcellular spatial gene expression (Xenium, n=41). Results: We performed multimodal spatial omics analysis of lung tissues along the NAT-aPML-LUAD continuum. After quality control, we retained and analyzed 477, 283 spots by ST, 401, 636 cells by scFFPE-seq, and more than 1.75 million cells by Xenium. Paired aPMLs and LUADs showed distinct spatial transcriptional patterns, lineage plasticity, and cell states. We derived nine metaprograms using scFFPE-seq data of epithelial cells, which showed robust alignment with sub-cell type and states from the ST data. Integrative analysis of ST and scFFPE-seq demarked metaprograms that denote alveolar type 1 (AT1) and type 2 (AT2), alveolar intermediate cell (AIC), and tumor cells in the cellular path to aPML and LUAD. Both LUAD and aPML regions highly expressed signatures of KRT8+ AICs (KACs), which denoted transitionary states between NATs and aPMLs or LUADs. Trajectory analysis demonstrated two alveolar transition paths, namely AT2-AIC-AT1 and AT2-KAC-lung tumors. In contrast to LUADs, early aPMLs and KAC-rich NAT expressed proinflammatory metaprograms, suggesting that interplay between KAC and inflammation is contextual and likely involved in tumor initiation in the peripheral lung. Spatial single-cell neighborhood analysis by Xenium platform concordantly showed that KACs were proximal to proinflammatory macrophages and cancer-associated fibroblasts (CAFs). Specifically, IL-1B+ proinflammatory macrophages and inflammatory CAFs were observed to be enriched in the neighborhood of tumor cells in aPMLs. Multimodal analysis of a tobacco lung carcinogenesis mouse model showed that KACs displayed increased NF-kB signaling and expression of the Il1b receptor Il1r1. Importantly, treatment with IL-1b or macrophage co-culture enhanced growth of KAC-enriched organoids, and IL-1b neutralization in vivo led to KAC regression. Conclusions: We generated a multimodal spatial and single-cell atlas of the transition of normal tissue to aPML and LUAD. This comprehensive atlas uncovered critical interactions between tumor progenitors and inflammation that inspire initiation of lung lesions and inform of unique and targetable cellular states for early detection and interception of LUAD. Citation Format: Fuduan Peng, Ansam Sinjab, Sujuan Yang, Yibo Dai, Minyue Chen, Warapen Treekitkarnmongkol, Tieling Zhou, Alejandra G. Serrano, Jianlong Liao, GuangSheng Pei, Yunhe Liu, Yang Liu, Jiahui Jiang, Kyung Serk Cho, Yanshuo Chu, Kai Yu, Ruiping Wang, Jiping Feng, Zahraa Rahal, Lorena I. Gomez Bolanos, Guangchun Han, Naoe Jimbo, Takuo Hayashi, Satsuki Kishikawa, Kazuya Takamochi, Akshay Basi, Avrum Spira, Steven Dubinett, Tomokazu Itoh, Takashi Yao, Kenji Suzuki, Luisa M. Solis, Stephen Swisher, Mingyao Li, Junya Fujimoto, Ignacio I. Wistuba, Jared Burks, Kadir Akdemir, Jeffrey Myers, Linghua Wang, Humam Kadara. Multimodal spatial-omics atlas of lung premalignancy and adenocarcinoma reveals tumor initiating interplay between alveolar progenitors and inflammation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 763.

  PublisherDOI

• Fostering Cultural Awareness in EFL Classrooms: Pedagogical Values and Implementation Approaches

  Literature Language and Cultural Studies · 2025-07-11

  articleOpen access1st authorCorresponding

  This study investigates the integration of cultural awareness in senior high school English Language Teaching (ELT), analyzing its pedagogical significance and implementation strategies. Grounded in English Curriculum Standards for Senior High Schools (Ministry of Education, PRC, 2017/2020 Revised Edition), the research identifies cultural awareness as a core competency encompassing intercultural knowledge, comparative analysis, and identity formation. The pa-per proposes a comprehensive framework featuring: (1) thematic cultural units, (2) authentic material utilization, (3) experiential learning activities, and (4) critical pedagogy approaches. Findings demonstrate that systematic cultural awareness cultivation enhances intercultural communication competence while reinforcing cultural confidence. The study highlights the necessity of teacher training and assessment reform for effective implementation. This research contributes to developing balanced ELT paradigms that harmonize linguistic proficiency with intercultural competence in globalized education contexts.

  PublisherDOI

• Scaling up spatial transcriptomics for large-sized tissues: uncovering cellular-level tissue architecture beyond conventional platforms with iSCALE

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-01 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Recent advances in spatial transcriptomics (ST) technologies have transformed our ability to profile gene expression while retaining the crucial spatial context within tissues. However, existing ST platforms suffer from high costs, long turnaround times, low resolution, limited gene coverage, and small tissue capture areas, which hinder their broad applications. Here we present iSCALE, a method that predicts super-resolution gene expression and automatically annotates cellular-level tissue architecture for large-sized tissues that exceed the capture areas of standard ST platforms. The accuracy of iSCALE were validated by comprehensive evaluations, involving benchmarking experiments, immunohistochemistry staining, and manual annotation by pathologists. When applied to multiple sclerosis human brain samples, iSCALE uncovered lesion associated cellular characteristics that were undetectable by conventional ST experiments. Our results demonstrate iSCALE's utility in analyzing large-sized tissues with automatic and unbiased tissue annotation, inferring cell type composition, and pinpointing regions of interest for features not discernible through human visual assessment.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HG005854

  NIH · $978k · 2015

• Elucidation of Tissue-Specific Transcriptomic Profiles in Cardio-metabolic Disease

  NIH · $6.8M · 2012–2024

• Computational and functional strategies to decipher lncRNAs in human atherosclerosis

  NIH · $2.7M · 2020–2025

• Statistical Methods for Transcriptome Profiling Using RNA Sequencing

  NIH · $1.2M · 2014–2020

• NIH Grant R01HG004517

  NIH · $1.9M · 2014

Frequent coauthors

• Muredach P. Reilly

  Columbia University Irving Medical Center

  271 shared

• Daniel J. Rader

  University of Pennsylvania

  189 shared

• Brendan J. Keating

  Miami Transplant Institute

  131 shared

• Jane F. Ferguson

  Vanderbilt University Medical Center

  130 shared

• Xuexia Wang

  101 shared

• Yan V. Sun

  Atlanta VA Health Care System

  100 shared

• Håkon Håkonarson

  University of Pennsylvania

  97 shared

• Alan R. Shuldiner

  Regeneron (United States)

  94 shared