About

Wenbao Yu, PhD, is a Research Assistant Professor of Pediatrics (Oncology) at the Children's Hospital of Philadelphia, affiliated with the Department of Pediatrics at the Perelman School of Medicine, University of Pennsylvania. His research expertise includes computational biology, single-cell multi-omics, cancer genomics, and 3D genome organization. Dr. Yu's work focuses on applying advanced computational methods to understand complex biological systems, particularly in the context of cancer and tumor microenvironments. His contributions include developing tools for single-cell chromatin accessibility sequencing data analysis and investigating the developmental trajectories of hematopoietic stem cell formation, as well as exploring tumor microenvironment rewiring in high-risk neuroblastoma. Dr. Yu has co-authored multiple publications in high-impact journals, emphasizing his role in advancing the understanding of cancer biology through innovative multi-omics approaches.

Research topics

• Computational biology
• Biology
• Computer Science
• Genetics
• Bioinformatics
• Pathology
• World Wide Web
• Medicine

Selected publications

• Abstract 4026: Spatial T-cell receptor profiling uncovers barriers to T-cell engagement and shared tumor-reactive clonotypes in high-risk neuroblastoma

  Cancer Research · 2026-04-03

  article

  Abstract Background: Survival for patients with high-risk neuroblastoma (NB) is ∼50%. While T-cell infiltration correlates with improved outcomes in some pediatric cancers, T-cell diversity, spatial organization, and antigen specificity remain poorly characterized. We integrated bulk T-cell receptor (TCR) sequencing, spatial transcriptomics, and spatial TCR profiling in NB patients from the Children's Oncology Group phase 3 trial ANBL1531, which evaluated 131I-metaiodobenzylguanidine therapy during frontline induction. Methods: We applied hybrid-capture TCR sequencing to paired biopsy and resection FFPE tumors (10 samples from 5 patients), longitudinal PBMCs (84 samples from 33 patients), and cfDNA (14 samples from 12 patients). Using shared TCRs across sample types and timepoints, we designed a Xenium panel with 377 genes and 100 TCRα/β/γ/δs, enabling spatial mapping across 1.90 million cells (median 138,742, range 17,175-715,510 cells per tumor). We predicted TCR specificity using MixTCRpred, and inferred sequence convergence using GLIPH2 against a database of reference TCRs (4,146 known specificities, 595,689 controls, 16,888 NB from the Precision oncology for young people cohort). Results: PBMC TCR repertoires showed biphasic dynamics, with diversity contracting mid-therapy (Shannon mean 476→151) then recovery post-therapy (413; p=0.0006, linear mixed-effects model), likely corresponding to chemotherapy-driven lymphopenia. In tumors, TCR diversity declined between biopsy and resection while hyperexpanded clonotypes increased (mean 30→59%), indicating potential selective clonal enrichment. Spatial profiling of the 10 tumors revealed immune-tumor compartmentalization, with macrophage-enriched barriers segregating immune cells from clusters of tumor cells. Spatial TCR profiling enabled in situ α/β chain pairing, identifying four TCRα/β clonotypes (all CD8+ effector memory) not resolvable by bulk sequencing. One clonotype with predicted NY-ESO-1 specificity expanded from biopsy to resection (2.22→4.92% of all T cells), suggesting antigen-driven clonal proliferation. Despite this expansion, clonotype spatial positioning remained unchanged, indicating that microenvironmental architecture constrains T-cell localization. GLIPH2 identified 8 NB-restricted TCR sequence motifs shared across 3-7 NB patients. These motifs occurred in individuals with convergent MHC alleles, suggesting recognition of common NB-associated antigens. Conclusions: Integrated TCR and spatial profiling revealed macrophage-mediated compartmentalization and restricted T-cell localization. Clonotypes predicted to be tumor-reactive also expanded during therapy. Shared NB-specific TCR motifs suggest convergent antigen recognition and targets for immunotherapy. Citation Format: Yiyue (January) Jiang, Wenbao Yu, Stephanie Pedersen, Jenna Eagles, Anusha Thadi, Arlene Naranjo, Natalie Bucheimer Collins, Steven DuBois, Rochelle Bagatell, Brian D. Crompton, Kai Tan, Trevor J. Pugh. Spatial T-cell receptor profiling uncovers barriers to T-cell engagement and shared tumor-reactive clonotypes in high-risk neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4026.

  PublisherDOI

• Unbiased weighing matrices of weight $9$

  ArXiv.org · 2025-01-26

  preprintOpen accessSenior author

  We investigate unbiased weighing matrices of weight $9$ and provide a construction method using mutually suitable Latin squares. For $n \le 16$, we determine the maximum size among sets of mutually unbiased weighing matrices of order $n$ and weight $9$. Notably, our findings reveal that $13$ is the smallest order where such pairs exist, and $16$ is the first order for which a maximum class of unbiased weighing matrices is found.

  PublisherOA PDFDOI

• Restraint of TGFβ family signaling by SMAD7 is necessary for hematopoietic stem cell maturation in the embryo

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-28

  preprintOpen access

  Abstract Hematopoietic stem cells (HSCs), defined as cells that can engraft an adult when transplanted, mature from precursors (pre-HSCs) that differentiate from hemogenic endothelial cells (HECs) in the embryo. Many signaling pathways required to generate the first hematopoietic stem and progenitor cells in the embryo are well-characterized, but how HSCs mature from pre-HSCs is poorly understood. Here we show that “mothers against decapentaplegic homolog 7” (SMAD7), a negative regulator of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) signaling, is required for pre-HSC to HSC maturation. Deletion of Smad7 in endothelial cells allows the formation of pre-HSCs from HECs but impairs their maturation into HSCs. The data indicate that although TGFβ and BMP signaling are required for the generation of HECs and for HECs to undergo an endothelial-to-hematopoietic transition to generate pre-HSCs, one or both pathways must be subsequently down-regulated for effective pre-HSC to HSC maturation.

  PublisherOA PDFDOI

• Exploring the Impact of Citric Acid on Mitigating Sweet Potato Soft Rot and Enhancing Postharvest Quality

  Agriculture · 2025-01-19 · 3 citations

  articleOpen access

  Citric acid (CAC) is a ubiquitous, odorless, and non-toxic food additive. Soft rot, caused by the pathogen Rhizopus stolonifer, is a major postharvest disease affecting sweet potato (Ipomoea batatas (L.) Lam). The main theme of this study is to determine the CAC inhibitory mechanism against Rhizopus stolonifer, the causative agent of sweet potato soft rot. To ascertain the practical applicability of CAC, both in vitro and in vivo methodologies were employed. The aim of the in vitro experiments in this study was to delineate the effects of a 0.5% (w/v) CAC solution on the growth inhibition of Rhizopus stolonifer, encompassing mycelial morphology and colony expansion. In vivo experiments were carried out using “Xinxiang” sweet potato varieties and the application of a 0.5% (w/v) CAC solution as a pretreatment. Specifically, the tissue treated with 0.5% CAC maintained better appearance quality and texture characteristics; peroxidase, β-1,3-glucanase, chitinase, and phenylalanine ammonia-lyase activities were enhanced. Conversely, the same treatment resulted in a downregulation of polyphenol oxidase, catalase, ascorbate peroxidase, cellulase, and polygalactosidase activities. Moreover, CAC treatment was found to maintain elevated levels of total phenolics and flavonoids within the sweet potato tissues. In summary, the study demonstrates that 0.5% CAC fortifies the resistance of sweet potato to soft rot by activating defense-related enzymes, suppressing the activity of cell wall-degrading enzymes, and promoting the accumulation of antimicrobial compounds. These results advocate for the utilization of CAC as a postharvest treatment to mitigate the incidence of sweet potato soft rot.

  PublisherOA PDFDOI

• Targeting senescent stemlike subpopulations in Philadelphia chromosome–like acute lymphoblastic leukemia

  Blood · 2025-01-07 · 9 citations

  articleOpen access

  ABSTRACT: Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) is driven by genetic alterations that induce constitutive kinase signaling and is associated with chemoresistance and high relapse risk in children and adults. Preclinical studies in the most common CRLF2-rearranged/JAK pathway-activated Ph-like ALL subtype have revealed variable responses to JAK inhibitor-based therapies, suggesting incomplete oncogene addiction and highlighting a need to elucidate alternative biologic dependencies and therapeutic vulnerabilities, whereas the ABL-class Ph-like ALL subtype seems preferentially sensitive to SRC/ABL- or PDGFRB-targeting inhibitors. Which patients may be responsive vs resistant to tyrosine kinase inhibitor (TKI)-based precision medicine approaches remains a critical knowledge gap. Using bulk and single-cell multiomics analyses, we profiled residual cells from CRLF2-rearranged or ABL1-rearranged Ph-like ALL patient-derived xenograft models treated in vivo with targeted inhibitors to identify TKI-resistant subpopulations and potential mechanisms of therapeutic escape. We detected a specific MYC dependency in Ph-like ALL cells and defined a new leukemia cell subpopulation with senescence-associated stem cell-like features regulated by AP-1 transcription factors. This dormant ALL subpopulation was effectively eradicated by dual pharmacologic inhibition of BCL-2 and JAK/STAT or SRC/ABL pathways, a clinically relevant therapeutic strategy. Single cell-derived molecular signatures of this senescence and stem/progenitor-like subpopulation further predicted poor clinical outcomes associated with other high-risk genetic subtypes of childhood B-ALL and thus may have broader prognostic applicability beyond Ph-like ALL.

  PublisherOA PDFDOI

• Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring

  Nature Genetics · 2025-04-14 · 23 citations

  articleOpen access1st authorCorresponding

  High-risk neuroblastoma, a leading cause of pediatric cancer mortality, exhibits substantial intratumoral heterogeneity, contributing to therapeutic resistance. To understand tumor microenvironment evolution during therapy, we longitudinally profiled 22 patients with high-risk neuroblastoma before and after induction chemotherapy using single-nucleus RNA and ATAC sequencing and whole-genome sequencing. This revealed profound shifts in tumor and immune cell subpopulations after therapy and identified enhancer-driven transcriptional regulators of neuroblastoma neoplastic states. Poor outcome correlated with proliferative and metabolically active neoplastic states, whereas more differentiated neuronal-like states predicted better prognosis. Proportions of mesenchymal neoplastic cells increased after therapy and a high proportion correlated with a poorer chemotherapy response. Macrophages significantly expanded towards pro-angiogenic, immunosuppressive and metabolic phenotypes. We identified paracrine signaling networks and validated the HB-EGF-ERBB4 axis between macrophage and neoplastic subsets, which promoted tumor growth through the induction of ERK signaling. These findings collectively reveal intrinsic and extrinsic regulators of therapy response in high-risk neuroblastoma.

  PublisherOA PDFDOI

• Restraint of TGF-β signaling by SMAD7 is necessary for the maturation of hematopoietic stem cells in the mouse embryo

  Blood · 2025-11-03

  article

  Abstract Hematopoietic stem and progenitor cells (HSPCs) in the mouse embryo arise from a subset of arterial hemogenic endothelial cells which bud into the lumen of the major vessels, forming intra-arterial hematopoietic cluster (IAHC) cells – a heterogenous population of non-HSC derived progenitors, the precursors of HSCs (pre-HSCs), and HSCs (Kissa and Herbomel 2010, Zhu, Gao et al. 2020). The first HSCs arise at embryonic day (E) 11.5 in the mouse embryo– almost 4 days after the onset of hematopoiesis and after hundreds of committed progenitors have already emerged (de Bruijn, Speck et al. 2000, Rybtsov, Sobiesiak et al. 2011, Gordon-Keylock, Sobiesiak et al. 2013, Rybtsov, Ivanovs et al. 2016). At E11.5, there are an estimated 65 pre-HSCs and 1 functional HSC (Rybtsov, Ivanovs et al. 2016). The rarity of these cells poses a significant challenge for identifying signals or genes required for their formation. We previously performed single-cell transcriptional profiling of endothelial cells, hemogenic endothelial cells, and HSPCs during hematopoietic development and found that a negative regulator of TGF-β signaling, Smad7, was specifically upregulated in pre-HSCs, suggesting that inhibition of TGF-β signaling may be necessary to generate pre-HSCs or HSCs. TGF-β signaling plays an essential role early in the specification of hemogenic endothelial cells, but how the restraint of TGF-β signaling affects the generation of pre-HSCs or their maturation into HSCs later in hematopoietic development is unknown. Deleting Smad7 at E9.5 using an endothelial-specific Cre (Smad7 KO) does not impact the number of IAHC cells or non-HSC-derived progenitors but results in a complete loss of functional adult-repopulating HSCs in the aorta-gonad-mesonephros region (AGM) in E11.5 Smad7 KOembryos. Limiting dilution transplants of E12.5 AGMs, which normally contain approximately 2-3 HSCs, revealed an 85% reduction in HSCs in Smad7 KOembryos compared to wild type embryos (0.52 HSCs/AGM Smad7 KO vs 2.56 HSCs/AGM WT, p=5.3e-6). HSPCs eventually migrate from the AGM to the fetal liver (FL). We observed a 60% reduction in HSCs in the E12.5 FL (11.0 HSCs/FL Smad7 KO vs 26.2 HSCs/FL WT, p=0.0167), suggesting that the reduction in HSCs in the AGM of Smad7 KO embryos is not the result of precocious migration of HSCs to the FL. Pre-HSCs are defined functionally as cells that cannot directly engraft an irradiated adult but can be matured ex vivo into adult repopulating cells. We performed a limiting dilution pre-HSC maturation assay by sorting IAHC cells from E11.5 embryos and found Smad7 KO IAHC cells had an 85% reduction in functional pre-HSCs (1:181 WT vs 1:1084 Smad7 KO, p=2.59e-5). We performed scRNA-seq profiling of wild type and Smad7 KO endothelial and IAHC cells at E11.5 to determine whether the generation of pre-HSCs was affected by loss of SMAD7. scRNA-seq revealed that the loss of SMAD7 increased the proportion of pre-HSCs relative to other hematopoietic cells by approximately 2-fold (p=0.003), indicating that pre-HSC formation was not affected and suggesting instead that pre-HSC to HSC maturation may be impaired. We directly examined the role of SMAD7 in pre-HSC maturation by deleting Smad7 with a ubiquitously expressed Rosa26CreERT after cells were sorted from E11.5 embryos. Ex vivo deletion of SMAD7 in pre-HSCs resulted in an 87% decrease in functional LT-HSCs (1:252 WT vs 1:1075 Smad7 KO, p=0.004), indicating that inhibiting TGF-β signaling is necessary for the proper maturation of pre-HSCs into HSCs but not their formation from endothelial cells. In summary, we identified the first signaling pathway in hematopoietic development that specifically promotes the maturation of HSCs from their embryonic precursors (pre-HSCs). Several groups have successfully demonstrated the ability to produce HSCs from iPSC cultures (Piau, Brunet-Manquat et al. 2023, Ng, Sarila et al. 2024). Understanding the signals required in the specification and maturation of HSCs in vivo during development, and when they should be applied and inhibited, will inform efforts to optimize HSC production from iPSCs.

  PublisherDOI

• Hemodynamic forces prevent myxomatous valve disease in mice through KLF2/4 signaling

  Journal of Clinical Investigation · 2025-06-15 · 2 citations

  articleOpen access

  Myxomatous valve disease (MVD) is the most common form of cardiac valve disease in the developed world. A small fraction of MVD is syndromic and arises in association with matrix protein defects such as those in Marfan syndrome, but most MVD is acquired later in life through an undefined pathogenesis. The KLF2/4 transcription factors mediate endothelial fluid shear responses, including those required to create cardiac valves during embryonic development. Here we test the role of hemodynamic shear forces and downstream endothelial KLF2/4 in mature cardiac valves. We find that loss of hemodynamic forces in heterotopically transplanted hearts or genetic deletion of KLF2/4 in cardiac valve endothelium confers valve cell proliferation and matrix deposition associated with valve thickening, findings also observed in mice expressing the mutant fibrillin-1 protein known to cause human MVD. Transcriptomic and histologic analysis reveals increased monocyte recruitment and TGF-β signaling in both fibrillin-1-mutant valves and valves lacking hemodynamic forces or endothelial KLF2/4 function, but only loss of TGF-β/SMAD signaling rescued myxomatous changes. We observed reduced KLF2/4 expression and augmented SMAD signaling in human MVD. These studies identify hemodynamic activation of endothelial KLF2/4 as an environmental homeostatic regulator of cardiac valves and suggest that non-syndromic MVD may arise in association with disturbed blood flow across the aging valve.

  PublisherDOI

• Unbiased weighing matrices of weight 9

  Designs Codes and Cryptography · 2025-06-28 · 1 citations

  articleOpen accessSenior author

  Abstract We investigate unbiased weighing matrices of weight 9 and provide a construction method using mutually suitable Latin squares. For $$n \le 16$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>n</mml:mi> <mml:mo>≤</mml:mo> <mml:mn>16</mml:mn> </mml:mrow> </mml:math> , we determine the maximum size among sets of mutually unbiased weighing matrices of order n and weight 9. Notably, our findings reveal that 13 is the smallest order where such pairs exist, and 16 is the first order for which a maximum class of unbiased weighing matrices is found.

  PublisherOA PDFDOI

• Constructions of Large m-Distance Sets on Triangular Lattice

  ArXiv.org · 2025-08-31

  preprintOpen accessSenior author

  An $m$-distance set is a collection of points such that the distances between any two points have $m$ possible values. We use two different methods to construct large $m$-distance sets on the triangular lattices. One is to use the first m smallest distances and find the largest cliques, and the other is using the notions of hexagons. Multiplicities of the distances were observed for comparison for the two methods.

  PublisherOA PDFDOI

Frequent coauthors

• Kai Tan

  Children's Hospital of Philadelphia

  70 shared

• Changya Chen

  Children's Hospital of Philadelphia

  29 shared

• Chia‐Hui Chen

  22 shared

• Yangyang Ding

  19 shared

• Kathrin M. Bernt

  Children's Hospital of Philadelphia

  18 shared

• Peng Gao

  18 shared

• Yasin Uzun

  Penn State Milton S. Hershey Medical Center

  17 shared

• Stephen P. Hunger

  15 shared

Labs

• Wenbao Yu LaboratoryPI

Education

• PhD, Statistics

  Chonnam National University

  2013

• Master, Mathematics

  University of Science and Technology of China

  2009

• Bachelor, Mathematics & Applied Mathematics

  Chongqing University

  2006