About

Yue Fan is an Associate Professor in the Department of Mechanical Engineering at the University of Michigan. His research focuses on defects behaviors and microstructural evolution in structural materials, deformation mechanisms, and the mechanical properties of amorphous solids, utilizing long time scale atomistic simulation. His work includes exploring the stability of metallic glasses through machine learning techniques and understanding the fundamental factors that influence amorphous materials, which have applications ranging from biomedical implants to industrial tools. Fan has received several awards and recognitions for his contributions to the field, including the NSF CAREER Award, the MPMD Young Leaders Professional Development Award from the Minerals, Metals, and Materials Society, and the ASME Haythornthwaite Young Investigator Award. His research has been published in prominent journals such as Physical Review Materials and Physical Review Letters, and he has been involved in studies that advance the understanding of dislocation-obstacle interactions and the mechanical behavior of nanocrystalline alloys. Since joining the faculty at Michigan in 2016, Yue Fan has established himself as a notable researcher in mechanics and materials, contributing to the advancement of knowledge in the behavior of complex materials.

Research topics

• Computer Science
• Biology
• Bioinformatics
• Computational biology
• Medicine
• Internal medicine
• Biochemistry
• Cell biology
• Genetics
• Pharmacology
• Chemistry

Selected publications

• Novel gene regulatory networks identified in response to nitro-conjugated linoleic acid in human endothelial cells

  Zenodo (CERN European Organization for Nuclear Research) · 2025-09-30

  datasetOpen access1st authorCorresponding

  A distinct transcriptome regulated by NO_2-CLA was revealed in primary human coronary artery endothelial cells (HCAECs) through RNA sequencing.

  PublisherDOI

• A clinical practice review: management strategies and emerging approaches for anastomotic leakage following radical surgery for esophageal cancer

  Annals of Palliative Medicine · 2025-09-01

  articleOpen access

  Radical esophagectomy remains the cornerstone of curative treatment for esophageal cancer, but is frequently complicated by postoperative events, most notably anastomotic leakage. Anastomotic leakage, occurring in up to 30% of cases, is multifactorial in origin and significantly increases morbidity and mortality. This review aims to summarize current management strategies, highlight emerging therapies, and identify persistent clinical challenges related to this complication. Relevant studies were identified through targeted literature searches of articles focusing on clinical management, therapeutic innovation, and reported outcomes related to anastomotic leakage, with an emphasis on recent and high-impact publications. This review synthesizes current strategies for the detection, prevention, and management of anastomotic leakage and evaluates emerging interventions. Early diagnosis through contrast-enhanced computed tomography (CT) and esophagography is critical for improving outcomes. Conservative measures such as broad-spectrum antibiotics, nutritional support, and image-guided drainage remain the first-line approach, while surgical revision and endoscopic techniques like stenting and vacuum therapy are increasingly employed in complex cases. Novel therapies, including tissue-engineered constructs and biodegradable stents, are under development but lack large-scale clinical validation. Despite these advancements, major clinical challenges persist, including limited predictive tools for risk stratification, variability in treatment algorithms across institutions, and unclear long-term efficacy of newer interventions. Furthermore, most novel strategies are supported by small cohort studies or preclinical data, limiting their immediate clinical application. Therefore, improved multidisciplinary collaboration, standardized treatment protocols, and integration of predictive diagnostics are essential for optimizing outcomes. Future research should focus on validating emerging therapies through randomized clinical trials and developing personalized management algorithms based on patient-specific risk factors and leak characteristics.

  PublisherDOI

• Endothelial Transcription Factor EB Protects Against Doxorubicin-Induced Endothelial Toxicity and Cardiac Dysfunction

  Circulation · 2025-12-18 · 1 citations

  articleOpen accessSenior author

  BACKGROUND: Doxorubicin (DOX), an effective chemotherapeutic drug for various cancers, has been demonstrated to induce cardiovascular toxicity in cancer survivors. Endothelial cell (EC) dysfunction is recognized to play a critical role in the onset and severity of cardiotoxicity associated with DOX. TFEB (transcription factor EB), a master regulator of autophagy and lysosome biogenesis, regulates cardiovascular homeostasis. In the present study, we aimed to test whether endothelial TFEB protects against EC damage and alleviates cardiac dysfunction induced by DOX treatment. METHODS: EC-specific TFEB transgenic mice, EC-specific TFEB knockout mice, and their corresponding littermate controls were administered DOX intravenously. Survival curves were generated, and cardiac functions were measured in mice. The effects of TFEB on mitochondrial reactive oxygen species production, autophagic flux, and apoptosis were evaluated in human and mouse cardiac microvascular ECs treated with DOX. RNA sequencing, single-cell RNA sequencing, and chromatin immunoprecipitation with quantitative polymerase chain reaction (ChIP-qPCR) was performed to dissect molecular mechanisms in DOX-treated ECs in vitro and in vivo. Mice with endothelium-specific deficiency of Dab2 gene (Disabled homolog 2) were subjected to measurement of cardiac function and fibrosarcoma growth under DOX treatment. RESULTS: EC-specific TFEB transgenic mice showed significantly reduced mortality and improved cardiac function, together with attenuation of perivascular fibrosis after DOX treatment. By contrast, EC-specific TFEB knockout exacerbated DOX-induced cardiac dysfunction in mice. Furthermore, we observed that TFEB enhanced autophagy and reduced oxidative stress in cardiac microvascular ECs treated with DOX. In addition, TFEB preserved EC barrier integrity, alleviated proinflammatory cytokine release from cardiac microvascular ECs, and maintained the EC–cardiomyocyte communication, contributing to the protective effects of EC TFEB on cardiomyocyte function. Mechanistically, DAB2, a clathrin- and cargo-binding endocytic adaptor protein, was identified as a TFEB target gene in ECs. Accordingly, DAB2 knockdown attenuated the inhibitory effects of TFEB on apoptosis and the secretion of proinflammatory cytokines from cardiac microvascular ECs. In vivo, EC-specific Dab2 deficiency abolished the protective effect of EC TFEB on DOX-induced cardiac dysfunction. CONCLUSIONS: Taken together, endothelial TFEB protects against EC damage and cardiac dysfunction, constituting a potential target for treating cardiotoxicity induced by DOX. Our study provides new mechanistic insights into cardiotoxicity associated with chemotherapy.

  PublisherOA PDFDOI

• Atg5 in microglia regulates sex-specific effects on postnatal neurogenesis in Alzheimer’s disease

  npj Aging · 2025-03-16

  articleOpen access

  Female Alzheimer's disease (AD) patients display greater cognitive deficits and worse AD pathology as compared to male AD patients. In this study, we found that conditional knockout (cKO) of Atg5 in female microglia failed to obtain disease-associated microglia (DAM) gene signatures in familiar AD mouse model (5xFAD). Next, we analyzed the maintenance and neurogenesis of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ) from 5xFAD mice with Atg5 cKO. Our data indicated that Atg5 cKO reduced the NSC number in hippocampus of female but not male 5xFAD mice. However, in the SVZ, Atg5 cKO only impaired NSCs in male 5xFAD mice. Interestingly, female 5xFAD;Fip200 cKO mice and 5xFAD;Atg14 cKO mice did not show NSC defects. These autophagy genes cKO 5xFAD mice exhibited a higher neurogenesis activity in their SVZ. Together, our data indicate a sex-specific role for microglial Atg5 in postnatal neurogenesis in AD mice.

  PublisherOA PDFDOI

• Novel gene regulatory networks identified in response to nitro-conjugated linoleic acid in human endothelial cells

  Zenodo (CERN European Organization for Nuclear Research) · 2025-09-30

  datasetOpen access1st authorCorresponding

  A distinct transcriptome regulated by NO_2-CLA was revealed in primary human coronary artery endothelial cells (HCAECs) through RNA sequencing.

  PublisherDOI

• Autophagy in alzheimer disease pathogenesis and its therapeutic values

  Autophagy Reports · 2025-05-08 · 10 citations

  reviewOpen access

  Alzheimer disease (AD) is the most common form of dementia with hallmarks of β-amyloid deposits, neurofilament tangles, synaptic loss and neuronal death in the patient's brain. AD is a heavy burden in an ageing society as there are no effective therapies in treating the causes or slowing down its progression. Autophagy is a conserved process through formation of double membrane structure, namely autophagosome which is delivered to lysosome to digest cellular disposals. Autophagy maintains homoeostasis in the brain and is generally considered to protect brain functions against ageing. The first evidence of autophagy involvement in AD is that there is decreased expression of autophagy essential genes in post-mortem AD brains. Autophagy is also believed to be protective in neurodegeneration. However, the molecular and cellular mechanisms for dysfunction of autophagy in AD are not fully understood. Recent studies of autophagy regulation in AD cover the findings not only in neurons, but also from fast growing evidence for their importance in glia and brain vascular system. Thus, this review composes pertinent information regarding the involvement of autophagy in neurons, glias (including microglia, astrocyte, and oligodendrocyte), and brain vascular cells in AD, and their unique cellular mechanisms of this connection in AD pathology. We will provide effectual insights both in investigating autophagy in AD pathological mechanisms and in establishing a strategic approach for developing autophagy-based AD therapies.

  PublisherDOI

• Clinical characteristics and prognostic analysis of patients with SMARCA4-deficient lung cancer

  Technology and Health Care · 2024-11-25 · 3 citations

  articleSenior author

  BackgroundSMARCA4-deficient NSCLC is a rare type of tumor, accounting for approximately 10% of all NSCLC. It exhibits a weak response to conventional chemotherapy and has a poor prognosis, and lacks alterations in EGFR (epidermal growth factor receptor), ALK (anaplastic lymphoma kinase), and ROS1 (ROS proto-oncogene 1) genes Therefore, the mechanisms of SMARCA4 in NSCLC development urgently need to be explored to identify novel biomarkers and precise therapeutic strategies for this subtype.ObjectiveThe aim of this study was to understand the clinical characteristics of this special type of tumor and its response to different treatments.MethodsWe collected clinical data from 42 patients with SMARCA4-deficient NSCLC from July 2022 to January 2024, and analyzed their clinical features and survival state.ResultsThe study included a total of 42 patients diagnosed with NSCLC and harboring SMARCA4 mutation. The majority of these patients were male with a median age of 67 years. Most patients presented at stage IV upon diagnosis with highly aggressive tumors characterized by high Ki-67 proliferation index values resulting in poor overall prognosis. Genetic testing revealed TP53 gene mutations to be most prevalent (21%), followed by KRAS mutations (13%). Patients receiving immunotherapy exhibited significantly longer median overall survival compared to those treated solely with chemotherapy. Targeted drug therapy demonstrated favorable effects in some patients.ConclusionNSCLC patients harboring SMARCA4 deficiency exhibit poor overall survival rates with a median overall survival time of 5.4 months. Immunotherapy may provide benefits for NSCLC patients with SMARCA4 deficiency.

  PublisherDOI

• Current Advances and Future Directions of Pluripotent Stem Cells-Derived Engineered Heart Tissue for Treatment of Cardiovascular Diseases

  Cells · 2024-12-18 · 8 citations

  reviewOpen access

  Cardiovascular diseases resulting from myocardial infarction (MI) remain a leading cause of death worldwide, imposing a substantial burden on global health systems. Current MI treatments, primarily pharmacological and surgical, do not regenerate lost myocardium, leaving patients at high risk for heart failure. Engineered heart tissue (EHT) offers a promising solution for MI and related cardiac conditions by replenishing myocardial loss. However, challenges like immune rejection, inadequate vascularization, limited mechanical strength, and incomplete tissue maturation hinder clinical application. The discovery of human-induced pluripotent stem cells (hiPSCs) has transformed the EHT field, enabling new bioengineering innovations. This review explores recent advancements and future directions in hiPSC-derived EHTs, focusing on innovative materials and fabrication methods like bioprinting and decellularization, and assessing their therapeutic potential through preclinical and clinical studies. Achieving functional integration of EHTs in the heart remains challenging due to the need for synchronized contraction, sufficient vascularization, and mechanical compatibility. Solutions such as genome editing, personalized medicine, and AI technologies offer promising strategies to address these translational barriers. Beyond MI, EHTs also show potential in treating ischemic cardiomyopathy, heart valve engineering, and drug screening, underscoring their promise in cardiovascular regenerative medicine.

  PublisherOA PDFDOI

• Macrophage-enriched Sectm1a promotes efficient efferocytosis to attenuate ischemia/reperfusion-induced cardiac injury

  JCI Insight · 2024-03-08 · 17 citations

  articleOpen accessCorresponding

  Efficient clearance and degradation of apoptotic cardiomyocytes by macrophages (collectively termed efferocytosis) is critical for inflammation resolution and restoration of cardiac function after myocardial ischemia/reperfusion (I/R). Here, we define secreted and transmembrane protein 1a (Sectm1a), a cardiac macrophage-enriched gene, as a modulator of macrophage efferocytosis in I/R-injured hearts. Upon myocardial I/R, Sectm1a-KO mice exhibited impaired macrophage efferocytosis, leading to massive accumulation of apoptotic cardiomyocytes, cardiac inflammation, fibrosis, and consequently, exaggerated cardiac dysfunction. By contrast, therapeutic administration of recombinant SECTM1A protein significantly enhanced macrophage efferocytosis and improved cardiac function. Mechanistically, SECTM1A could elicit autocrine effects on the activation of glucocorticoid-induced TNF receptor (GITR) at the surface of macrophages, leading to the upregulation of liver X receptor α (LXRα) and its downstream efferocytosis-related genes and lysosomal enzyme genes. Our study suggests that Sectm1a-mediated activation of the Gitr/LXRα axis could be a promising approach to enhance macrophage efferocytosis for the treatment of myocardial I/R injury.

  PublisherOA PDFDOI

• BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-03-02 · 4 citations

  preprintOpen access

  The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence of pancreatic cancer stem-like cells (CSCs) that respond poorly to current chemotherapy regimens. By small molecule compound screening targeting 142 epigenetic enzymes, we identified that bromodomain-containing protein BRD9, a component of the BAF histone remodelling complex, is a key chromatin regulator to orchestrate the stemness of pancreatic CSCs via cooperating with the TGFβ/Activin-SMAD2/3 signalling pathway. Inhibition and genetic ablation of BDR9 block the self-renewal, cell cycle entry into G0 phase and invasiveness of CSCs, and improve the sensitivity of CSCs to gemcitabine treatment. In addition, pharmacological inhibition of BRD9 significantly reduced the tumorigenesis in patient-derived xenografts mouse models and eliminated CSCs in tumours from pancreatic cancer patients. Mechanistically, inhibition of BRD9 disrupts enhancer-promoter looping and transcription of stemness genes in CSCs. Collectively, the data suggest BRD9 as a novel therapeutic target for PDAC treatment via modulation of CSC stemness.

  PublisherOA PDFDOI

Recent grants

• Alleviation of chemotherapy-induced cardiovascular toxicity

  NIH · $1.4M · 2024–2028

• The role of TFEB in aortic aneurysms

  NIH · $2.2M · 2020–2025

• Transcription Factor-EB and Postischemic Angiogenesis

  NIH · $2.2M · 2020–2023

Frequent coauthors

• Jifeng Zhang

  University of Michigan–Ann Arbor

  100 shared

• Wei Wang

  Sun Yat-sen University

  96 shared

• Minerva T. Garcia-Barrio

  University of Michigan–Ann Arbor

  51 shared

• Tianqing Zhu

  City University of Macau

  48 shared

• Y. Eugene Chen

  Michigan Center for Translational Pathology

  48 shared

• Yanhong Guo

  University of Michigan–Ann Arbor

  44 shared

• Y. Eugene Chen

  University of Yamanashi

  41 shared

• Nanping Wang

  East China Normal University

  41 shared

Education

• Bachelor , Clinical Medicine

  Hebei Medical University

• Ph.D., Physiology

  Peking University

  2008

Awards & honors

• MPMD Young Leaders Professional Development Award (2021)
• Doctoral New Investigator grant from the American Chemical S…
• NSF CAREER Award (2020)
• Physical Review Materials publication
• Physical Review Letters publication