A5100698888- Immune cells in cancer
- Chemokine receptors and signaling
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Inflammation biomarkers and pathways
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Vasculitis and related conditions
- Ubiquitin and proteasome pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Cytomegalovirus and herpesvirus research
- Cell Adhesion Molecules Research
- Renal Diseases and Glomerulopathies
- Virus-based gene therapy research
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- SARS-CoV-2 and COVID-19 Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Herpesvirus Infections and Treatments
- Cancer, Hypoxia, and Metabolism
The Ohio State University
2021-2025
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2021-2025
Versiti Blood Center of Wisconsin
2015-2024
Comprehensive Blood & Cancer Center
2024
Ningbo University
2024
Changzhou Institute of Technology
2024
The Ohio State University Wexner Medical Center
2022-2023
Ohio University
2023
Ningxia University
2022
Medical College of Wisconsin
2019
Abstract Single-cell multi-omics (scMulti-omics) allows the quantification of multiple modalities simultaneously to capture intricacy complex molecular mechanisms and cellular heterogeneity. Existing tools cannot effectively infer active biological networks in diverse cell types response these external stimuli. Here we present DeepMAPS for network inference from scMulti-omics. It models scMulti-omics a heterogeneous graph learns relations among cells genes within both local global contexts...
Robust and effective T cell immune surveillance cancer immunotherapy require proper allocation of metabolic resources to sustain energetically costly processes, including growth cytokine production. Here, we show that asparagine (Asn) restriction on CD8
Abstract Rare cell populations are key in neoplastic progression and therapeutic response, offering potential intervention targets. However, their computational identification analysis often lag behind major types. To fill this gap, we introduce MarsGT: Multi-omics Analysis for population inference using a Single-cell Graph Transformer. It identifies rare probability-based heterogeneous graph transformer on single-cell multi-omics data. MarsGT outperforms existing tools identifying cells...
Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the cell response; however, molecular pathways which sustains immunity remain unclear. We demonstrate that causes phenotypic switch transcription factor expression during infection characterized sustained BATF expression. Importantly, both required for optimal persistence and anti-viral effector function sufficient to rescue "unhelped"...
Abstract Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4 + T follicular helper (Tfh) cells main subset regulating autoreactive B cells. Here we report a CXCR5 PD1 Tfh CD8 whose development and function negatively modulated Stat5. These regulate germinal center cell response control autoantibody production, as deficiency Stat5 in leads to an increase cells, resulting breakdown tolerance concomitant production. share similar gene...
Effective T cell-mediated immune responses require the proper allocation of metabolic resources to sustain growth, proliferation, and cytokine production. Epigenetic control genome also governs cell transcriptome lineage commitment maintenance. Cellular programs interact with epigenetic regulation by providing substrates for covalent modifications chromatin. By using complementary genetic, epigenetic, approaches, we revealed that tricarboxylic acid (TCA) cycle flux fueled biosynthetic...
Mycobacterium tuberculosis (Mtb) and SARS-CoV-2 (CoV2) are the leading causes of death due to infectious disease. Although Mtb CoV2 both cause serious sometimes fatal respiratory infections, effect infection its associated immune response on secondary with is unknown. To address this question we applied two mouse models COVID19, using mice which were chronically infected Mtb. In model systems, Mtb-infected resistant pathological consequences infection, did not affect burdens. Single cell RNA...
Optimal activation of CD8+ T cells is crucial for immunity-mediated destruction cancer, requiring a substantial amount proteins involved in metabolism, proliferation, and effector function. Despite extensive studies emphasizing the role transcriptional regulation this process, paired transcriptomic proteomic analyses reveal that RNA profile poorly correlated with protein levels. This discrepancy underscores importance post-translational modifications (PTMs) controlling abundance during...
Abstract During chronic viral infection, the inflammatory function of CD4 T-cells becomes gradually attenuated. Concurrently, Th1 cells progressively acquire capacity to secrete cytokine IL-10, a potent suppressor antiviral T cell responses. To determine transcriptional changes that underlie this adaption process, we applied single-cell RNA-sequencing approach and assessed heterogeneity IL-10-expressing during infection. Here show an IL-10-producing population with robust Tfh-signature....
There is a strong correlation between myeloid-derived suppressor cells (MDSC) and resistance to immune checkpoint blockade (ICB), but the detailed mechanisms underlying this are largely unknown. Using single-cell RNA sequencing analysis in bilateral tumor model, we found that immunosuppressive myeloid with characteristics of fatty acid oxidative metabolism dominate immune-cell landscape ICB-resistant subjects. In addition, uncovered previously underappreciated role serine/threonine kinase,...
Single-cell multi-omics (scMulti-omics) has brought transformative insights into immuno-oncology, demonstrating success in describing novel immune subsets and defining important regulators of antitumor immunity. Here, we give examples how scMulti-omics been used specific tumor studies discuss this may develop the future.
Abstract During intracellular infection, T follicular helper (T FH ) and 1 H 1) cells promote humoral cell-mediated responses, respectively. Another subset, CD4-cytotoxic lymphocytes (CD4-CTLs), eliminate infected via functions typically associated with CD8 + cells. The mechanisms underlying differentiation of these populations are incompletely understood. Here, we identify the transcription factor Aiolos as a reciprocal regulator CD4-CTL programming. We find that deficiency results in...
Abstract Introduction As one of the major components tumor microenvironment, tumor-associated macrophages (TAMs) possess profound inhibitory activity against T cells and facilitate escape from immune checkpoint blockade therapy. Converting this pro-tumorigenic toward anti-tumorigenic phenotype thus is an important strategy for enhancing adaptive immunity cancer. However, a plethora mechanisms have been described differentiation in cancer, metabolic switches to program property TAMs are...
Intratumoral regulatory T cells (Tregs) are key mediators of cancer immunotherapy resistance, including anti-PD-(L)1 immune checkpoint blockade (ICB). The mechanisms driving Treg infiltration into the tumor microenvironment (TME) and consequence on CD8+ cell exhaustion remains elusive. Herein, we report that heat shock protein gp96 (GRP94) is indispensable for infiltration, primarily through gp96's roles in chaperoning integrins. Among various gp96-dependent integrins, found only LFA-1 (αL...
The O -GlcNAc transferase (OGT) is an essential enzyme that mediates protein -GlcNAcylation, a unique form of posttranslational modification many nuclear and cytosolic proteins. Recent studies observed increased OGT -GlcNAcylation levels in broad range human cancer tissues compared to adjacent normal tissues, indicating universal effect promoting tumorigenesis. Here, we show for tumor growth immunocompetent mice by repressing the cyclic GMP-AMP synthase (cGAS)-dependent DNA sensing pathway....
Patients with anti-glomerular basement membrane (GBM) disease were predominantly reported in Caucasian population and reports from Chinese lacking. The general picture of patients anti-GBM was still unclear. This study is to investigate the characteristics prognosis disease.Data 105 diagnosed our hospital, between 1997 2002, analyzed retrospectively. All sera screened by enzyme-linked immunosorbent assay (ELISA) using highly purified bovine alpha(IV)NC1 as solid phase ligands. Clinical...
In cancer, CD8+ T cells enter a dysfunctional state which prevents them from effectively targeting and killing tumor cells. Tumor-infiltrating consist of heterogeneous population memory-like progenitor, effector, terminally exhausted that exhibit differing functional self-renewal capacities. Our recently published work has shown interleukin (IL)-21-producing CD4+ help to generate effector within the tumor, results in enhanced control. However, molecular mechanisms by helper regulate...