A5062735403- Immune Cell Function and Interaction
- Immune cells in cancer
- Hematopoietic Stem Cell Transplantation
- Atherosclerosis and Cardiovascular Diseases
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Complement system in diseases
- Pulmonary Hypertension Research and Treatments
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Inflammation biomarkers and pathways
- Cardiovascular Function and Risk Factors
- Computational Fluid Dynamics and Aerodynamics
- Advanced Numerical Methods in Computational Mathematics
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiovascular Disease and Adiposity
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Apelin-related biomedical research
- Electromagnetic Simulation and Numerical Methods
- Liver Disease and Transplantation
- Multiple Sclerosis Research Studies
University of Minnesota
2022-2024
National Institutes of Health
2017-2023
Center for Cancer Research
2017-2023
Bipar
2023
National Cancer Institute
2017-2023
University of Minnesota Medical Center
2022
Institute of Immunology
2021-2022
Mayo Clinic in Florida
2017-2018
WinnMed
2017
Hartford Financial Services (United States)
1990
Posttransplantation cyclophosphamide (PTCy) recently has had a marked impact on human allogeneic hematopoietic cell transplantation (HCT). Yet our understanding of how PTCy prevents graft-versus-host disease (GVHD) largely been extrapolated from MHC-matched murine skin-allografting models that were highly contextual in their efficacy. Herein, we developed T cell–replete, MHC-haploidentical, HCT model (B6C3F1→B6D2F1) to test the putative underlying mechanisms: alloreactive elimination,...
Abstract Atherosclerosis is driven by the expansion of cholesterol-loaded ‘foamy’ macrophages in arterial intima. Factors regulating foamy macrophage differentiation and survival plaque remain poorly understood. Here we show, using trajectory analysis integrated single-cell RNA sequencing data a genome-wide CRISPR screen, that triggering receptor expressed on myeloid cells 2 (Trem2) associated with specification. Loss Trem2 led to reduced ability take up oxidized low-density lipoprotein...
BACKGROUND: Trem2 (triggering receptor on myeloid cells 2), a surface lipid receptor, is expressed foamy macrophages within atherosclerotic lesions and regulates cell survival, proliferation, anti-inflammatory responses. Studies examining the role of in atherosclerosis have shown that deletion leads to impaired macrophage uptake, cholesterol efflux. Thus, we tested hypothesis administration agonist antibody (AL002a) atherogenic mice would enhance survival decrease necrotic core formation...
Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species generation, results in peroxidation ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation macrophage recruitment. In pulmonary arterial hypertension (PAH), endothelial cells exhibit cellular phenotypes promote Moreover, there ectopic deposition accumulation the vasculature. However, effects ferroptosis inhibition on these pathogenic...
Posttransplantation cyclophosphamide (PTCy), given on days +3 and +4, reduces graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), but its immunologic underpinnings are not fully understood. In a T-cell-replete, major histocompatibility complex-haploidentical murine HCT model (B6C3F1→B6D2F1), we previously showed that PTCy rapidly induces suppressive mechanisms sufficient to prevent GVHD induction by non-PTCy-exposed donor splenocytes infused day +5....
Pancreatic ductal adenocarcinoma (PDA) orchestrates a suppressive tumor microenvironment that fosters immunotherapy resistance. Tumor-associated macrophages (TAMs) are the principal immune cell infiltrating PDA and heterogeneous. Here, by employing macrophage fate-mapping approaches single-cell RNA sequencing, we show monocytes give rise to most subsets in PDA. Tumor-specific CD4, but not CD8, T cells promote monocyte differentiation into MHCIIhi anti-tumor macrophages. By conditional major...
Post-transplantation cyclophosphamide (PTCy) reduces the risks of severe acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Yet, standard clinical dose timing PTCy were partly extrapolated from MHC-matched skin allografting models empirical. Here we investigated impact differential dosing on its efficacy in preventing GVHD a murine MHC-haploidentical HCT model. Administration days +3/+4 was superior to administration +1/+2, +5/+6, or...
Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome, but predominant subset of HFpEF patients has metabolic syndrome (MetS). Mechanistically, systemic, nonresolving inflammation associated MetS might drive remodeling. Free fatty acid receptor 4 (Ffar4) GPCR for long-chain acids that attenuates dysfunction and resolves inflammation. Therefore, we hypothesized Ffar4 would attenuate remodeling in secondary to (HFpEF-MetS). To test this hypothesis, mice systemic...
Glucocorticoid synthesis by adrenal glands (AGs) is regulated the hypothalamic-pituitary-adrenal axis to facilitate stress responses when host exposed stimuli. Recent studies implicate macrophages as potential steroidogenic regulators, but molecular mechanisms which AG exert such influence remain unclear. In this study, we investigated role of in response cold challenge or atherosclerotic inflammation physiologic models acute chronic stress. Using single-cell RNA sequencing, observed dynamic...
We investigate how myeloid subsets differentially shape immunity to pancreatic ductal adenocarcinoma (PDA). show that tumor antigenicity sculpts cell composition and functionality. Antigenicity promotes accumulation of type 1 dendritic cells (cDC1), which is driven by Xcr1 signaling, overcomes macrophage-mediated suppression. The therapeutic activity adoptive T therapy or programmed death ligand blockade required cDC1s, sustained splenic Klrg1+ cytotoxic antitumor functional intratumoral...
Aim: To evaluate the long-term safety and efficacy of ab-interno trabeculectomy with trabectome for treatment glaucoma.Materials methods: Data collected 339 eyes which included demographics, intraocular pressure (IOP) measurements using Goldmann applanation tonometry, best-corrected visual acuity (BCVA), field results, optic nerve status, gonioscopic findings, prior glaucoma procedures, number medications pain level.The main data points interest were preoperative IOP vs. postoperative BCVA,...
Abstract Background Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species (ROS) generation, results in peroxidation ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation macrophage recruitment. In pulmonary arterial hypertension (PAH), endothelial cells (PAEC) exhibit cellular phenotypes promote Moreover, there ectopic deposition accumulation the vasculature. However, effects ferroptosis...
Abstract Objective Trem2, a surface lipid receptor, is expressed on foamy macrophages within atherosclerotic lesions and regulates cell survival, proliferation, anti-inflammatory responses. Studies examining the role of Trem2 in atherosclerosis have shown that deletion leads to impaired macrophage uptake, cholesterol efflux. Thus, we tested hypothesis administration validated agonist antibody (AL002a) atherogenic mice could drive survival decrease necrotic core formation improve plaque...
Relapse limits the therapeutic efficacy both of chimeric antigen receptor (CAR) T cells and allogeneic hematopoietic cell transplantation (allo-HCT). Patients may undergo these therapies sequentially to prevent or treat relapsed malignancy. However, direct integration 2 has been avoided over concerns for potential induction graft-versus-host disease (GVHD) by CAR cells. We have shown in murine T-cell-replete MHC-haploidentical allo-HCT that suppressive mechanisms induced immediately after...
Abstract Atherosclerotic plaque formation is driven by the continued expansion of cholesterol loaded ‘foamy’ macrophages within arterial intima. Foamy are primarily derived from newly recruited monocytes, but factors regulating monocyte specification toward foamy macrophage differentiation and prolonged survival in remain poorly understood. We used trajectory analysis integrated single cell RNA-seq data, along with a genome-wide CRISPR screening approach to identify Triggering Receptor...
The purpose of this article is to evaluate the improved safety and efficacy transscleral cyclophotocoagulation (TSCPC) by performing it in operating room. This a retrospective review 17 eyes 16 patients who received TSCPC for uncontrolled glaucoma on maximum tolerated medication. Mean intraocular pressure (IOP) prior surgery was 30.85 ± 6.24 mm Hg reduced 14.48 3.53 after treatment an average reduction IOP 48.56% at final visit (P < .001). Visual acuity measured follow-up stable 13 (76.47%),...
Abstract Pancreatic ductal adenocarcinoma (PDA) is a particularly lethal malignancy that lacks effective therapeutic strategies. A promising modality can elicit transient antitumor responses in subset of metastatic PDAs chemotherapy + CD40 agonist +/- anti-PD-1. deeper understanding the cellular mechanisms mediate initial will inform new strategies to enhance durability this therapy. Our prior studies demonstrated tumor-specific CD4 T cells are critical for mitigating tumor growth syngeneic...
Recruited monocytes that subsequently differentiate into macrophages within atherosclerotic lesions are a primary driver of plaque progression and risk factor for rupture. Advances in single cell RNA sequencing have expanded our understanding macrophage diversity plaques. However, limited analysis has explored regulators monocyte lineage commitment spatial localization plaque. Examining scRNAseq gene expression data plaque-associated lineages, pseudotime trajectory predicted binary fate...
Atherosclerosis is an inflammatory disease of the arteries that a major cause cardiovascular (CVD). Atherosclerotic plaque progression driven by deposition low-density lipoprotein (LDL) within intima, which internalized macrophages, forming lipid-engorged foamy cells. Importantly, accumulation excess LDL macrophages cytotoxic, driving apoptosis, ultimately promotes necrotic core formation and increased potential for rupture. Recently, our lab identified lipid receptor Trem2 to be highly...