A5059994496- Liver Disease Diagnosis and Treatment
- Immune Cell Function and Interaction
- Pancreatitis Pathology and Treatment
- Sphingolipid Metabolism and Signaling
- Diabetes and associated disorders
- Immune cells in cancer
- Liver Diseases and Immunity
- Inflammation biomarkers and pathways
- Atherosclerosis and Cardiovascular Diseases
- IL-33, ST2, and ILC Pathways
- Cardiac Fibrosis and Remodeling
- Lipid metabolism and biosynthesis
- Apelin-related biomedical research
- Exercise and Physiological Responses
- Adipokines, Inflammation, and Metabolic Diseases
- Fibroblast Growth Factor Research
- Advanced battery technologies research
- Autophagy in Disease and Therapy
- Congenital heart defects research
- Pancreatic function and diabetes
- Asthma and respiratory diseases
- GDF15 and Related Biomarkers
- Tissue Engineering and Regenerative Medicine
- Neuroinflammation and Neurodegeneration Mechanisms
- Peptidase Inhibition and Analysis
University of Minnesota
2020-2024
University of Minnesota System
2023
University of Minnesota Medical Center
2021-2023
Health Net
2023
The initial hypertrophy response to cardiac pressure overload is considered compensatory, but with sustained stress, it eventually leads heart failure. Recently, a role for recruited macrophages in determining the transition from compensated decompensated has been established. However, whether resident immune cells influence early phase of development not established.To assess induced by transverse aortic constriction (TAC).We performed cytometry time-of-flight determine identity and...
Background and Aims Nonalcoholic steatohepatitis is rapidly becoming the leading cause of liver failure indication for transplantation. Hepatic inflammation a key feature NASH but immune pathways involved in this process are poorly understood. B lymphocytes cells adaptive system that critical regulators responses. However, role pathogenesis potential mechanisms to their activation unclear. Approach Results In study, we report livers accumulate with elevated pro‐inflammatory cytokine...
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...
Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of pathology ranging from simple to non-alcoholic steatohepatitis (NASH). Notably, immune cell-driven inflammation is key mechanism in the transition more serious NASH. Although exercise training effective ameliorating obesity-related diseases, underlying mechanisms beneficial effects remain unclear. It unknown whether there an optimal modality and intensity treat NAFLD. The objective this study was determine high-intensity...
For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating dysfunction-associated steatohepatitis (MASH). While the effects of surgeries been mainly attributed to nutrient restriction malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Using murine models, we report that VSG ameliorates MASH progression weight loss-independent manner. Single-cell RNA sequencing revealed...
Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid associated with nonalcoholic steatohepatitis (NASH). Immune cell-driven inflammation key determinant of NASH progression. Macrophages, monocytes, NK cells, T NKT and B cells variably express S1P receptors from repertoire 5 termed 1 – . We have previously demonstrated that non-specific receptor antagonism ameliorates attenuates hepatic macrophage accumulation. However, the effect on additional immune cell populations in remains...
ABSTRACT Inflammation is a significant risk factor and contributes to cardiovascular disease by driving both adaptive maladaptive processes. Macrophages are the most abundant immune cells in heart play an important role remodeling of cardiac tissue. We have previously shown overall protective function resident macrophages after pressure-overloaded injury. However, subpopulation also expresses high levels profibrotic CC motif chemokine ligand 24 (CCL24), suggesting dichotomous pressure...
Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of lipid droplets in hepatocytes. NAFLD development and progression associated with an increase hepatic cholesterol levels decreased autophagy lipophagy flux. Previous studies have shown that expression lysosomal acid lipase (LAL), encoded gene LIPA, which can hydrolyze both triglyceride cholesteryl esters, inversely correlated severity NAFLD. In addition, ablation LAL activity results profound Based on this, we...
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...
For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating dysfunction-associated steatohepatitis (MASH). While the effects of surgeries been mainly attributed to nutrient restriction malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Here we report that VSG ameliorates MASH progression weight loss-independent manner. Single-cell RNA sequencing revealed hepatic...
ABSTRACT Nonalcoholic steatohepatitis (NASH), characterized by hepatic inflammation and cellular damage, is the most severe form of nonalcoholic fatty liver disease fastest-growing indication for a transplant. The intestinal immune system central modulator local systemic inflammation. In particular, Peyer’s patches (PPs) contain T follicular helper (Tfh) cells that support germinal center (GC) responses required generation high-affinity IgA maintenance homeostasis. However, our understanding...
ABSTRACT B cells play a crucial role in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH), severe form steatotic liver disease that if persistent can lead to cirrhosis, failure, and cancer. Chronic inflammation fibrosis are key features MASH determine progression outcomes. Recent advances have revealed pathogenic cell-derived cytokines antibodies promote development MASH. However, mechanisms through which adaptations underlying their responses remain unclear. Here,...
ABSTRACT For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating dysfunction-associated steatohepatitis (MASH). While the effects of surgeries been mainly attributed to nutrient restriction malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Here we report that VSG ameliorates MASH progression weight loss- independent manner. Single-cell RNA sequencing revealed hepatic...
Abstract The intestinal immune system is a central modulator of obesity-associated metabolic disease. Particularly, high-affinity IgA maintains gut homeostasis after its generation in germinal center (GC) response that requires functional T follicular helper (Tfh) cells Peyer’s patches (PP). objective this study was to determine how obesity affects Tfh function leading We investigated the phenotype diet-induced obese mice. Obese mice showed enlarged PP featured by an expansion CXCR5 highICOS...
Hepatic inflammation, driven by immune cells such as B and T lymphocytes, is a hallmark feature of metabolic dysfunction-associated steatohepatitis (MASH). Here, we detail robust cytometry time-of-flight (CyTOF) procedure to phenotype hepatic lymphocytes from mice with MASH. We employ custom metal conjugation antibodies, isolation cell surface intracellular staining, data acquisition. This protocol overcomes the limitations traditional flow accommodating up 40 markers for comprehensive...
Abstract In the past few decades, higher rates of obesity have coincided with a rising number individuals affected by allergic disease. Our study objective was to determine if alters immune cell landscape small intestine towards an inflammatory environment that aggravates development food allergy. Obesity induced feeding male BALB/c mice western diet for 8 weeks. To induce allergy, were epicutaneously sensitized and orally-challenged OVA. Compared lean controls, obese showed lower body...
Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of lipid droplets (LD) in hepatocytes. If untreated, NAFLD can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, or hepatocellular carcinoma. The progression NASH associated with increases cholesterol levels and decreased autophagy lipophagy flux. Previous studies have shown that expression lysosomal acid lipase (LAL), which hydrolyze both triglyceride cholesteryl esters, inversely correlates severity...