About

Wenli Yang, PhD, is a Research Assistant Professor of Medicine in Translational Medicine and Human Genetics at the University of Pennsylvania Perelman School of Medicine. He is a member of the Institute for Regenerative Medicine (IRM), the Institute for Translational Medicine and Therapeutics (ITMAT), and the Cardiovascular Institute (CVI). Dr. Yang is the Director of the iPSC Core Facility at the University of Pennsylvania School of Medicine and has over 15 years of experience in developing human cellular models of disease using induced pluripotent stem cells (iPSCs). His group has generated hiPSC lines from more than 150 normal and diseased human subjects and employs CRISPR/Cas9 technology for genetic modifications in PSCs, including gene reporters, knock-outs, and single base knock-ins. His research focuses on establishing robust protocols for differentiating PSCs into various cell lineages such as cardiomyocytes, hepatocytes, endothelial cells, adipocytes, skeletal muscle cells, and pancreatic beta cells. Dr. Yang played a key role in a NIH-funded project demonstrating that stem cell-derived hepatocyte-like cells are a powerful model for studying complex human diseases. His core collaborates extensively within Penn and externally to facilitate research in cardiomyocyte biology, lung regeneration, hepatocyte biology, muscle regeneration, and type 1 diabetes. His active research program aims to understand how type 2 diabetes risk variants and effector genes influence disease development, developing and validating human PSC-cell models of adipose, muscle, and liver tissues to establish functional assays of insulin action. His work links genotype to phenotype and investigates mechanisms of action of T2D-associated variants and pathways, particularly in skeletal muscle using human cell models.

Research topics

• Biology
• Cell biology
• Genetics
• Virology
• Medicine
• Immunology
• Biochemistry
• Pharmacology

Selected publications

• UCHL3 Promotes Triple-Negative Breast Cancer Metastatic Potential Through Enhancing Cell Migration and Invasion

  Applied Biochemistry and Biotechnology · 2026-04-07

  article
  PublisherDOI

• Osteoradionecrosis after mandibular reconstruction: a comparative cohort study on quality of life and complications

  Frontiers in Oncology · 2026-02-04

  articleOpen accessSenior author

  Objective: This study aimed to compare longitudinal quality of life (QoL) and surgical outcomes following segmental mandibulectomy and free fibula flap reconstruction among patients with osteoradionecrosis (ORN), malignant disease, and benign conditions. Methods: A comparative cohort study was conducted involving 245 patients: 45 with ORN, 160 with malignancy, and 40 with benign disease. Patient-reported QoL was assessed using the EORTC QLQ-C30 and QLQ-H&N35 questionnaires preoperatively and at 3, 6, and 12 months postoperatively. The primary outcomes were 12-month Global Health Status (QLQ-C30) and Pain scores (QLQ-H&N35), analyzed using multivariable linear regression. The secondary outcome was the incidence of major surgical complications (Clavien-Dindo ≥ III), analyzed using multivariable logistic regression. Results: At 12 months, the ORN cohort demonstrated significantly worse QoL outcomes compared to the benign cohort, with a -14.1-point lower Global Health Status (95% CI: -19.5 to -8.7, p<0.001) and a +21.5-point higher Pain score (95% CI: +15.2 to +27.8, p<0.001), after multivariable adjustment. The ORN cohort also had the highest rate of major complications (48.9% vs. 17.5% benign, p<0.001), which remained significant in multivariable analysis (aOR for benign vs. ORN: 0.26, p=0.006). Larger bony defect length and longer operative time were independent predictors of poorer QoL and higher complication risk, while the use of virtual surgical planning was associated with better Global Health Status. Conclusion: Despite successful reconstruction, patients with ORN experience profoundly poorer long-term QoL, persistent pain, and a significantly higher complication burden compared to patients with benign or malignant disease. These findings highlight the unique challenges in ORN management and underscore the need for specialized long-term supportive care.

  PublisherOA PDFDOI

• The E3 ligase HECTD1 controls skeletal muscle sarcomere and mitochondrial integrity

  Research Square · 2026-03-08

  preprintOpen access
  PublisherOA PDFDOI

• The molecular prognostic scoring system for normal karyotype myelodysplastic syndromes

  Journal of Translational Medicine · 2025-01-16 · 1 citations

  articleOpen access

  BACKGROUND: Molecular-clinical prognostic models for Myelodysplastic syndromes (MDS) offer more accurate prognosis predictions, yet existing models often overlook the heterogeneity of mutational profiles against the cytogenetic background. Moreover, how to apply these models in regions where large panel NGS is unaffordable remains a significant challenge to be addressed. METHODS: A total of 237 NK MDS patients from our center were used as the training set to screen for key variables and develop a prognostic model with overall survival (OS) as the endpoint. The C-index was used as the main evaluation metric to assess the model's performance. The IWG-PM cohort (n = 691) was used as an external independent validation set to evaluate the generalizability of the model. RESULTS: We developed a seven-parameter molecular-clinical prognostic model, the Molecular Prognostic Scoring System for NK MDS (NK-PSS-M), which only incorporates three gene mutations as parameters. The NK-PSS-M can reliably predict OS and leukemia-free survival (LFS). The performance of NK-PSS-M was comparable to that of the Molecular International Prognostic Scoring System (IPSS-M), and it significantly outperformed the Revised International Prognostic Scoring System for MDS (IPSS-R). CONCLUSIONS: The NK-PSS-M model improved the risk stratification of non-molecular models and provided a reliable alternative to the IPSS-M. This strategy provides insights into how resource-scarce regions can apply molecular-clinical models.

  PublisherOA PDFDOI

• Role, mechanisms and effects of <i>Radix Bupleuri</i> in anti‑breast cancer (Review)

  Oncology Letters · 2025-01-30 · 3 citations

  reviewOpen accessSenior author

  The prevalence of breast cancer among women has led to a growing need for innovative anti‑breast cancer medications and an in‑depth investigation into their molecular mechanisms of action, both of which are essential tactics in clinical intervention. In the clinical practice of Traditional Chinese Medicine, <em>Radix Bupleuri</em> and its active components have shown promise as potential anti‑breast cancer agents due to their ability to target multiple pathways, exhibit synergistic effects and reduce toxicity. These compounds are considered to enhance the prognosis of patients with cancer, prolong survival and combat chemotherapy resistance. The present review aimed to delve into the anti‑breast cancer properties of <em>Radix Bupleuri</em> and its active ingredients, highlighting their mechanisms, such as inhibition of cell proliferation, promotion of apoptosis, metastasis prevention, microenvironment improvement and synergy with certain chemotherapeutic agents. These findings may provide a scientific rationale for combining <em>Radix Bupleuri</em> and its active components with traditional chemotherapy agents for the management of breast cancer.

  PublisherOA PDFDOI

• 3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility

  Genome biology · 2025-12-08 · 1 citations

  articleOpen access

  Abstract Background Insight into the genetic basis for many common autoimmune disorders has been uncovered by genome-wide association studies (GWAS), but this alone does not reveal causal variants, effector genes, or the cell types impacted by disease-associated variation. Results Here, we generate 3D genomic datasets consisting of promoter-focused Capture-C, Hi-C, ATAC-seq, and RNA-seq and integrate this data with GWAS of 16 autoimmune traits to physically map disease-associated variants to the effector genes they likely regulate in 57 human cell types. The majority of variants implicated by these cis-regulatory architectures are trait-specific, but nearly half of the target genes connected to these variants are shared across multiple autoimmune disorders in multiple cell types, leading to enrichment of similar biological networks. While this suggests a high level of genetic diversity and complexity that converges at the level of target gene and cell type, some trait-specific pathways representing potential areas for disease-specific intervention were identified. We pharmacologically validate squalene synthase, a cholesterol biosynthetic enzyme encoded by the FDFT1 gene implicated by our approach and supported by prior eQTL data in multiple sclerosis and systemic lupus erythematosus, as a novel immunomodulatory drug target controlling T cell inflammatory cytokine production and aiding B cell antibody production in a human lymphoid organoid model. Conclusions These data represent a comprehensive resource for basic discovery of gene cis-regulatory mechanisms, and the analyses reported reveal mechanisms by which autoimmune-associated variants act to regulate gene expression, function, and pathology across multiple, distinct tissues and cell types. Graphical Abstract

  PublisherDOI

• Safety and efficacy of selinexor sequential azacytidine in newly diagnosed patients with myelodysplastic syndromes EB1 or EB2: A single-center, single-arm, phase ib/II trial

  Blood · 2025-11-03

  article

  Abstract Background: Higher-risk MDS (HR-MDS), defined by the Revised International Prognostic Scoring System (IPSS-R) as intermediate, high, or very-high-risk disease, has a median overall survival of less than two years. HMAs yield low complete response (CR) rates and are associated with transient responses, often leading to disease progression or relapse. There is a critical unmet need for novel, well-tolerated, and more effective therapies for HR-MDS. Selinexor is an oral, first-in-class selective inhibitor of nuclear export compound that inhibits exportin 1 (XPO1). Our preclinical studies have shown that Azacytidine sequential Selinexor had strong synergetic effect in MDS both in vitro and in vivo. Methods: We conducted a single-center, single-arm, phase Ib/II trial in newly diagnosed patients with MDS-EB1 or EB2. The primary endpoints of phase Ib trial were to find the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of Selinexor. The primary endpoint of phase II trial was to access the overall response rate (ORR) including complete remission (CR), partial remission (PR), marrow complete remission (mCR), and hematological improvement (HI) according to International Working Group criteria (IWG) 2006. Secondary key endpoints of phase II trial included the followings: (1) safety and tolerability of Azacytidine sequential Selinexor; (2) cytogenetic response and molecular response. Results: Between Sept 6, 2022 and January 5, 2025, 12 patients were enrolled in phase Ib study and 27 patients were enrolled in phase II study. At Phase Ib, the following selinexor dosages were administered: 60mg biw (n=3), 60mg qw (n=3), 40mg biw (n=3) and 40mg qw (n=3). Two patients in the 60mg biw group discontinued treatment because of grade 3 nausea, vomiting and anorexia, which reached the MTD. One patient in the 60mg qw group discontinued treatment because of nausea, vomiting, fatigue and Herpes simplex virus infection. The most common grade 3 or 4 adverse events (AEs) of phase Ib study were hematologic toxicities: neutropenia (100%), thrombocytopenia (66.7%) and anemia (25.0%). The most common non-hematologic AEs were: fatigue (58.3%), anorexia (50.0%), nausea (41.6%), vomiting (41.6%), hypocalcemia (41.6%), dizziness (33.3%), hyponatremia (25.0%). Totally, 36 patients included in the phase Ib/II trial were evaluable for efficacy assessment. According to the IWG 2006 response criteria, ORR was 94.4%, including 14 CR (38.9%), 7 mCR+HI (19.4%) and 13 mCR (36.1%). For 17 patients with TP53 mutations, ORR was 100%, including 8 CR (47.1%), 4 mCR+HI (23.5%) and 5 mCR (29.4%). Patients with TP53 mutations achieved higher CR than patients with TP53 wildtype (47.1% vs. 31.6%), though is not significant (P=0.342). Interestingly, among 23 patients with abnormal karyotypes, eleven patients (47.8%) achieved complete cytogenetic response (cCyR) and six patient (26.1%) achieved partial cytogenetic response (pCyR). The overall cytogenetic response rate (CyR) was 73.9%. Among the 16 patients with complex karyotypes (14 concurrent with TP53 mutation), 7 patients (43.8%) achieved cCyR and 6 patients (37.5%) achieved pCyR. The overall cytogenetic response rate was 81.3%. Among the 15 patients achieved CR or mCR+HI and received more than two cycles of AS regimen, including 8 patients with TP53 mutations using a VAF cutoff of 5%, 7 (87.5%) patients achieved NGS negativity and 1 patient had an obvious VAF decrease. Additionally, the patients with U2AF1, NPM1, RUNX1, WT1, BCOR, CBL, SF3B1 and PTPN11 mutations also achieved NGS negativity. At a median follow-up time of 23.8 months, the median OS in all the patients was not reached and the median PFS was 24.2 months (11.0~NR). The 2-year OS and PFS for all 36 patients were 83.7% and 50.1%, respectively. The median OS between TP53 mutant and wild-typed patients was not significantly different (NR [95% CI, 10.8m to NR] vs. NR [95% CI, NR]; P=0.096). The median PFS between TP53 mutant and wild-typed patients was not significantly different, either (9.23 months [95% CI, 5.3m to NR] vs. 24.43 months [95% CI, 18.1m to NR]; P=0.074). Conclusion: Azacitidine sequential Selinexor regimen demonstrated a high response rate and was tolerable in newly diagnosed patients with MDS-EB1 or EB2. The patients with TP53 mutations had a higher CR rate and longer PFS and OS compared with literatures. The patients who achieved CR also obtained high cytogenetic and molecular biology response.

  PublisherDOI

• Evidence summary of meaning in life intervention for cancer patients

  Frontiers in Oncology · 2025-07-30 · 1 citations

  reviewOpen access

  Objective: To evaluate and summarize evidence on intervention of the meaning of life of cancer patients, and provide evidence-based basis for clinical practice. Methods: According to the "6S" evidence model, The literature related to the life meaning intervention in cancer patients were systematically searched in domestic and foreign evidence-based resource databases,comprehensive databases and professional society websites from the inception of database to Oct 2023. Two researchers evaluated the quality of the literature, extracted and integrated evidence. Results: A total of 28 articles were included, including 2 the computer decisions, 4 guidelines, 7 systematic evaluations, 6 quasi-experimental studies, and 9 randomized controlled trials. A final total of 48 pieces of evidence were summarized, including 5 areas of organizational management, assessment, evaluation indicators, intervention programs for meaning of life, and intervention techniques. Conclusion: This study forms the evidence of intervention of the meaning of life of cancer patients, which can provide reference for clinical practice, Individualized treatment and nursing care should be provided according to the symptoms and actual needs of the patients, and relevant evidence should be updated in time.

  PublisherOA PDFDOI

• Dissecting Cellular Dynamics Following Radiation-Induced Lung Injury via Single-Cell RNA Sequencing

  International Journal of Radiation Oncology*Biology*Physics · 2025-09-01

  article1st authorCorresponding
  PublisherDOI

• Cyclodextrin Counteracts Coxsackievirus-Induced Cardiac Damage by Protecting Desmosome Integrity and Suppressing Proinflammatory Cytokine Expression

  Microorganisms · 2025-10-02

  articleOpen access

  Nuclear factor of activated T cells 5 (NFAT5), an osmosensitive transcription factor, has been shown to protect against coxsackievirus B3 (CVB3)-induced myocarditis but is susceptible to cleavage by viral proteases. Identifying agents that upregulate NFAT5 may offer a novel antiviral strategy. Cyclodextrins, cyclic oligosaccharides that influence cellular osmolality, are promising candidates. In this study, we demonstrate that NFAT5 is critical for maintaining desmosomal integrity in cardiomyocytes. Cardiac-specific Nfat5-knockout mice showed a significant reduction in desmosomes, as observed by transmission electron microscopy. Furthermore, we identified desmoplakin (DSP), a structural desmosomal protein, as a direct transcriptional target of NFAT5, with reduced expression in Nfat5-knockout mouse hearts and NFAT5-knockdown HeLa cells. Notably, treatment with 5 mM cyclodextrin significantly upregulated NFAT5 expression with minimal cytotoxicity, restored DSP expression, and suppressed CVB3 replication by inhibiting viral RNA transcription, protein synthesis, and virion production. Additionally, cyclodextrin reduced mRNA levels of proinflammatory cytokines interleukin-1 beta and interleukin-8, indicating its potential role as an alleviator of excessive cytokine production. These findings identify NFAT5 as a key regulator of desmoplakin expression and prove cyclodextrin as a dual-functioning agent in counteracting cardiac damage through NFAT5-DSP-mediated protection of desmosome integrity and suppressing proinflammatory cytokine expression in CVB3-induced myocarditis.

  PublisherOA PDFDOI

Recent grants

• Functional Interrogation of T2D-associated genes in human stem cell-derived models and mice

  NIH · $8.8M · 2020–2026

Frequent coauthors

• Edward E. Morrisey

  University of Pennsylvania

  61 shared

• Bruce M. Spiegelman

  Dana-Farber Cancer Institute

  59 shared

• Daniel J. Rader

  University of Pennsylvania

  39 shared

• Christoph Handschin

  University of Basel

  38 shared

• Julie St‐Pierre

  University of Ottawa

  35 shared

• Hongyan Tong

  Zhejiang University

  31 shared

• Rachel Truitt

  California University of Pennsylvania

  29 shared

• Jiandie D. Lin

  University of Michigan–Ann Arbor

  26 shared

Labs

• iPSC Core Facility, University of PennsylvaniaPI

Education

• PhD

  University of California Los Angeles

  2001