About

Bo Zhang is an Assistant Professor of Instruction in the Department of Earth, Environmental, and Planetary Sciences at Northwestern University. He received his PhD in Geography from the University of Connecticut in 2021, with a background in environmental science and GIS. His research interests center on applying geospatial technologies to study physical environment change, with a focus on the development and application of Markov chain geostatistics. His previous work has investigated spatiotemporal patterns of aerosol particles, transit accessibility, and transportation network analysis. Bo Zhang has also worked as a GIS analyst for a project assessing service equity in Connecticut's large public transportation systems. He is involved in teaching courses such as First Year Seminar, Data Analysis for Earth & Environmental Sciences, Scientific Programming in Python, and GIS Level 1 and 2.

Research topics

• Biology
• Cancer research
• Medicine
• Internal medicine
• Immunology
• Genetics
• Bioinformatics
• Computational biology
• Cell biology

Selected publications

• Bi-specific T cell-engaging antibody triggers protective immune memory and glioma microenvironment remodeling in immune-competent preclinical models

  Journal for ImmunoTherapy of Cancer · 2025-10-01 · 2 citations

  articleOpen access

  BACKGROUND: Bispecific T cell-engagers (BTEs) are engineered antibodies that redirect T cells to target antigen-expressing tumors. BTEs targeting tumor-specific antigens such as interleukin 13 receptor alpha 2 (IL13RA2) and epidermal growth factor receptor variant III (EGFRvIII) have been developed for glioblastoma (GBM). However, there is limited mechanistic understanding of the action of BTE since prior studies were mostly conducted in immunocompromised animal models. To close this gap, the function of BTEs was assessed in the immunosuppressive tumor microenvironment (TME) of orthotopic and genetically engineered mouse models (GEMM) with intact immune systems. METHODS: A BTE that bridges CD3 epsilon on murine T cells to IL13RA2-positive GBM cells was developed, and the therapeutic mechanism was investigated in immunocompetent mouse models of GBM. Multicolor flow cytometry, single-cell RNA sequencing (scRNA-seq), multiplex immunofluorescence, and multiparametric MRI across multiple preclinical models of GBM were used to evaluate the mechanism of action and response. RESULTS: BTE-mediated interactions between murine T cells and GBM cells triggered T cell activation and antigen-dependent killing of GBM cells. BTE treatment significantly extended the survival of mice bearing IL13RA2-expressing orthotopic glioma and de novo forming GBM in the GEMM. Quantified parametric MRI validated the survival data, showing a reduction in glioma volume and decreased glioma viability. Flow cytometric and scRNA-seq analyses of the TME revealed robust increases in activated and memory T cells and decreases in immunosuppressive myeloid cells within the brains of mice following BTE treatment. CONCLUSIONS: Our data demonstrate that the survival benefits of BTEs in preclinical models of glioma are due to the ability to engage the host immune system in direct killing, induction of immunological memory, and modulation of the TME. These findings provide a deeper insight into the mechanism of BTE actions in GBM.

  PublisherOA PDFDOI

• SATB1 is a key regulator of quiescence in stem-like CD8+ T cells

  Nature Immunology · 2025-08-22 · 12 citations

  articleOpen access
  PublisherOA PDFDOI

• DNA methylation predicts adverse outcomes of coronary artery disease

  Nature Communications · 2025-12-12 · 2 citations

  articleOpen access

  Adverse outcomes including myocardial infarction (MI) and stroke render coronary artery disease (CAD) a leading cause of death worldwide. DNA methylation markers may alert such adversity ahead of the events. We profiled DNA methylation of blood leukocytes in 933 Chinese CAD patients with up-to-13-year follow-up from three centers, identifying 70 differentially methylated sites (DMPs) associated with future death. These DMPs correlated with inflammation markers, left ventricular functions and high-density lipoprotein cholesterol, and impacted gene expression in immune response and cellular scenesence. Notably, cg25563198 and cg25114611 were discovered to regulate FKBP5, whose upregulation persisted during MI and stroke. Fkbp5 knockout in male mice partially rescued MI by reducing infarct size and improving heart function, confirming its critical function. Finally, our prognostic model of 10 methylation sites and 5 clinical features outperformed clinical models. Our study highlights the value of DNA methylation in predicting prognosis in CAD and provides tools for clinical translation.

  PublisherOA PDFDOI

• Imrecoxib attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway

  Frontiers in Bioengineering and Biotechnology · 2025-04-28 · 5 citations

  articleOpen access

  Introduction: Although biomaterials strategies have been regarded as a promising approach for the treatment of osteoarthritis (OA), identifying novel drugs to be delivered for modulate macrophage polarization is still unclear. As a commonly used non-steroidal anti-inflammatory drug for OA, Imrecoxib may be a novel drug to direct and sustain macrophage phenotype. However, the specific protective mechanism of Imrecoxib in OA remains unclear. This study aims to investigate whether Imrecoxib would treat OA by regulating synovial macrophage polarization. Methods: The research involves constructing mouse destabilization of medial meniscus (DMM) model to assess the changes in pain, bone destruction, cartilage degeneration, and synovial macrophage phenotypes following Imrecoxib treatment. Additionally, the effects of macrophage conditioned medium (CM) pretreated with Imrecoxib on the chondrocyte apoptosis, inflammation and degeneration-related factor expression were evaluated. The role of COX-2/PGE2 signaling pathway in the macrophage phenotype changes was further investigated. Results: experiments, Imrecoxib-CM protected chondrocyte by modulating macrophage polarization. Furthermore, Imrecoxib regulates macrophage polarization through the COX-2/PGE2 pathway. Conclusion: This study unravels that Imrecoxib protects joint cartilage and attenuates osteoarthritis by modulating synovial macrophage polarization through inactivating COX-2/PGE2 signaling pathway, providing new drug delivery strategy for the clinical treatment of OA.

  PublisherOA PDFDOI

• Low expression of CADPS predicts poor prognosis in pediatric acute lymphoblastic leukemia without fusion genes

  Biomolecules and Biomedicine · 2025-05-30 · 1 citations

  articleOpen access1st authorCorresponding

  Pediatric acute lymphoblastic leukemia (ALL) is among the most prevalent hematological malignancies in children. Despite an overall cure rate approaching 90%, a subset of patients still experiences relapse, even with advanced therapeutic interventions. Research into the molecular characteristics and prognostic markers of fusion gene-negative (FG-negative) pediatric ALL remains limited. To address this gap, we performed whole-exome sequencing (WES) and whole-transcriptome sequencing (RNA-seq) on 54 FG-negative ALL cases from our center. Our results indicated that neither specific mutations nor tumor mutational burden significantly influenced relapse risk. Notably, we identified a significant downregulation of CADPS in FG-negative pediatric ALL patients who relapsed. The expression levels and prognostic significance of CADPS were further validated using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) cohort, where lower CADPS expression was associated with reduced event-free survival (EFS) and overall survival (OS) (P < 0.001 for both). Cox regression analyses were subsequently employed to identify OS-related factors and to construct a prognostic prediction model. Notably, this model demonstrated a significant correlation with therapeutic targets. In conclusion, our findings support the potential of CADPS expression as a novel biomarker for prognostic stratification in FG-negative pediatric ALL patients.

  PublisherOA PDFDOI

• Genome-wide identification of selection signals in fat-tailed and thin-tailed sheep populations

  Frontiers in Genetics · 2025-10-17

  articleOpen access

  Introduction In the evolutionary context of sheep, the development of fat tails represents an adaptive survival mechanism in response to varying food availability. Despite food resource instability, sheep store energy by accumulating tail fat to survive periods of famine. This energy storage function remains present in domesticated sheep, serving as a key evolutionary reason for the formation of sheep tail fat. Methods Here, we conducted whole-genome resequencing of 555 sheep samples (30 samples were newly sequenced and 525 were retrieved from published data) globally to investigate selection signatures associated with fat-tailed traits using Fixation Index (F ST ), Nucleotide diversity (π), cross-population composite likelihood ratio (XP-CLR), and runs of homozygosity (ROH) methods. Result and discussion Our examination of selection signatures in Fat-tailed and Thin-tailed Sheep Populations identified 32 candidate genes, with 6 genes ( PDGFD , BMP2 , GLIS1 , LIPE , MSRB3 , and TBX15 ) implicated in fat accumulation and lipid metabolism. Notably, 8 significant Gene Ontology terms (mesenchymal cell differentiation, positive regulation of ERK1 and ERK2 cascades, hormone metabolic process, nucleocytoplasmic transport, regulation of hormone levels, response to growth factor, regulation of canonical Wnt signaling pathway, and tissue morphogenesis) may play a role in fat deposition and tail fat development. These results will provide molecular targets for low-fat sheep breeding and enhance economic returns in sheep farming. Conclusion This study will play a crucial role in environmental adaptation and product development, comprehensively driving the development of the sheep farming industry and enhancing economic benefits.

  PublisherOA PDFDOI

• HMGB1 inhibits the IFN-γ–induced PD-L1 expression in NSCLC

  The Journal of Immunology · 2025-06-28 · 1 citations

  article

  T cells are the most important cytotoxic cells involved in antitumor immune responses. After recognizing the major histocompatibility complex (MHC)-peptide complex, cytokines including interferon-γ (IFN-γ) are released to kill tumor cells. However, IFN-γ can also induce tumor cells to express PD-L1. This molecule can bind to PD-1 on the surface of T cells to exert inhibitory functions. In response to stimuli, like chemoradiotherapy or immunotherapy, tumor cells release damage-associated molecular patterns, including high-mobility group protein B1 (HMGB1). Our previous studies revealed that HMGB1 can increase the antitumor activity of T cells and enhance the secretion of cytokines, including IFN-γ. However, the effect of HMGB1 on PD-L1 expression in non-small cell lung cancer remains unclear. Here, we examined the expression of HMGB1 and PD-L1 in tumor tissue slices of patients with non-small cell lung cancer with high expression of IFN-γ and observed that they exhibited a negative correlation, which was also verified by our analysis in The Cancer Genome Atlas. In vitro experiments demonstrated that HMGB1 could bind to RAGE (receptor for advanced glycation end products) and inhibit IFN-γ induction of PD-L1 by inhibiting the JAK1/STAT3 pathway. In vitro and in vivo experiments indicated that HMGB1 enhanced the antitumor effects of chimeric antigen receptor T cells and inhibited tumor growth. These results showed that HMGB1 inhibited IFN-γ-induced PD-L1 expression, thereby enhancing the antitumor effects of T cells, and confirmed the role of HMGB1 as a prognostic indicator for lung cancer treated with chimeric antigen receptor T cells.

  PublisherDOI

• Overcoming treatment resistance mediated by the bone marrow vascular niche in acute myeloid leukemia

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-24

  preprintOpen access

  Abstract Acute myeloid leukemia (AML) is a hematologic malignancy originating in the bone marrow, frequently progressing to extramedullary sites. Despite advances in molecularly targeted therapies and hematopoietic stem cell transplantation, clinical outcomes remain suboptimal. Tyrosine kinase inhibitors (TKIs) confer benefit in a subset of AML patients harboring FLT3-ITD mutations, yet relapse and resistance are common. These failures are driven by both intrinsic properties of leukemic stem cells (LSCs)—a quiescent, self-renewing population—and extrinsic cues from the tumor microenvironment. We previously demonstrated that arteriolar endothelial cells (ECs) produce miR-126, which is transferred to LSCs, promoting quiescence, treatment resistance, and niche retention. During disease progression, TNF-α secreted by expanding blasts suppresses EC miR-126 production, enabling LSCs and their progeny to proliferate. Following TKI administration, blast reduction lowers TNF-α levels, restoring EC miR-126 production and enabling LSCs to re-enter quiescence—thereby escaping therapy and facilitating relapse. To investigate this dynamic, we developed an agent-based computational model of the AML bone marrow microenvironment, parameterized with in vitro and in vivo data. The model captures vascular niche remodeling and the feedback between leukemic populations and endothelial signaling. Simulations reveal that LSC protection mediated by miR-126 can be overcome by combining TKIs with miRisten, a miR-126 inhibitor. When administered on a defined schedule, this combination disrupts the protective niche and enhances LSC eradication. These findings underscore the therapeutic potential of targeting microenvironmental feedback to overcome resistance and prevent AML relapse.

  PublisherOA PDFDOI

• Multispectral, omics, and structural analysis of crispy pork ribs: Effects of combined pretreatment with different proteases on multidimensional quality characteristics

  LWT · 2025-12-01

  articleOpen access

  This study combined multispectral analysis, microstructural characterization, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and untargeted metabolomics to investigate the effects of pretreatment with different protease combinations on the quality characteristics and compositions of crispy pork ribs and elucidate the corresponding mechanisms. The results indicate that crispy pork ribs pretreated with various enzyme combinations exhibited higher pH and moisture content, lower frying loss, and texture characteristic values. Endogenous fluorescence spectroscopy, ultraviolet–visible absorption spectroscopy, and secondary structural analysis of myofibrillar proteins (MPs) demonstrated that protease pretreatment promoted protein degradation and induced structural unfolding. SDS-PAGE results further confirm that protease pretreatment accelerated protein degradation, which led to considerably reduced and optical density values in high- and low-molecular-weight bands, respectively. Untargeted metabolomics findings show that pretreatment with different enzymes promoted a significant increase in the relative content of substance components that contributed positively to the taste of crispy pork ribs (such as 16-hydroxy hexadecanoic acid, nicotinic acid, glutaric acid, etc.). Comprehensive evaluation demonstrated that pretreatment with compound enzyme formulation (papain + bromelain + collagenase) yielded the most substantial improvement in the quality characteristics of crispy pork ribs. • Effects of enzyme combination pretreatment on crispy pork ribs quality were assessed. • Pretreatment with three enzyme combinations promoted protein degradation in pork ribs. • Pretreatment with enzyme combinations increased characteristic taste compounds in pork ribs. • The papain–bromelain–collagenase pretreatment resulted in the best improved quality of crispy pork ribs.

  PublisherDOI

• MGAT1-Guided complex N-Glycans on CD73 regulate immune evasion in triple-negative breast cancer

  Nature Communications · 2025-04-14 · 9 citations

  articleOpen access

  Abstract Despite the widespread application of immunotherapy, treating immune-cold tumors remains a significant challenge in cancer therapy. Using multiomic spatial analyses and experimental validation, we identify MGAT1, a glycosyltransferase, as a pivotal factor governing tumor immune response. Overexpression of MGAT1 leads to immune evasion due to aberrant elevation of CD73 membrane translocation, which suppresses CD8 + T cell function, especially in immune-cold triple-negative breast cancer (TNBC). Mechanistically, addition of N-acetylglucosamine to CD73 by MGAT1 enables the CD73 dimerization necessary for CD73 loading onto VAMP3, ensuring membrane fusion. We further show that THBS1 is an upstream etiological factor orchestrating the MGAT1-CD73-VAMP3-adenosine axis in suppressing CD8 + T cell antitumor activity. Spatial transcriptomic profiling reveals spatially resolved features of interacting malignant and immune cells pertaining to expression levels of MGAT1 and CD73. In preclinical models of TNBC, W-GTF01, an inhibitor specifically blocked the MGAT1-catalyzed CD73 glycosylation, sensitizing refractory tumors to anti-PD-L1 therapy via restoring capacity to elicit a CD8 + IFNγ-producing T cell response. Collectively, our findings uncover a strategy for targeting the immunosuppressive molecule CD73 by inhibiting MGAT1.

  PublisherDOI

Recent grants

• WEE1 inhibition and tumor immunity

  NIH · $2.2M · 2018–2024

• A deubiquitination module controls Treg adaptation to tumor microenvironment

  NIH · $2.8M · 2021–2026

• NIH Grant R01CA149669

  NIH · $1.7M · 2016

• The role of GPSM3 in tumor-promoting emergency myelopoiesis

  NIH · $1.8M · 2017–2023

Frequent coauthors

• Yi Zhang

  Shanghai Changzheng Hospital

  152 shared

• Siqi Chen

  Sun Yat-sen Memorial Hospital

  93 shared

• Jie Fan

  62 shared

• Dongli Yue

  First Affiliated Hospital of Zhengzhou University

  53 shared

• Donye Dominguez

  52 shared

• Xinfeng Chen

  47 shared

• Lei Qin

  45 shared

• Tyler J. Curiel

  38 shared

Labs

• Bo Zhang LabPI