A5015253891- Wound Healing and Treatments
- Immune cells in cancer
- Atherosclerosis and Cardiovascular Diseases
- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- Diabetic Foot Ulcer Assessment and Management
- Pressure Ulcer Prevention and Management
- T-cell and B-cell Immunology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cytokine Signaling Pathways and Interactions
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Clinical practice guidelines implementation
- Signaling Pathways in Disease
- IL-33, ST2, and ILC Pathways
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- Adipokines, Inflammation, and Metabolic Diseases
- Liver physiology and pathology
- interferon and immune responses
- Immune Cell Function and Interaction
- Aortic aneurysm repair treatments
- Inflammasome and immune disorders
- CAR-T cell therapy research
University of Michigan
2015-2025
Michigan United
2018-2024
Center for Vascular Biology Research
2020-2024
Ann Arbor VA Medical Center
2022-2023
Ann Arbor Center for Independent Living
2022
Michigan Medicine
2021-2022
Center for Rheumatology
2019
Düsseldorf University Hospital
2015
University of North Carolina at Chapel Hill
2015
Heinrich Heine University Düsseldorf
2014-2015
Macrophage plasticity is critical for normal tissue repair following injury. In pathologic states such as diabetes, macrophage impaired, and macrophages remain in a persistent proinflammatory state; however, the reasons this are unknown. Here, using single-cell RNA sequencing of human diabetic wounds, we identified increased JMJD3 wound macrophages, resulting inflammatory gene expression. Mechanistically, report that healing, directs early macrophage-mediated inflammation via JAK1,3/STAT3...
Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is lack of effective therapy preventing rupture. During AAA formation, pathological vascular remodeling driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays critical role in establishing phenotype. Using single-cell RNA sequencing human tissues, we identified increased JMJD3...
Macrophages are a primary immune cell involved in inflammation, and their plasticity allows for transition from an inflammatory to reparative phenotype is critical normal tissue repair following injury. Evidence suggests that epigenetic alterations play role establishing macrophage function during pathologic wound repair. Here, we find human murine macrophages cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) elevated diabetes regulates downstream macrophage-mediated inflammation host defense....
Autoimmune disease is 4 times more common in women than men. This bias largely unexplained. Female skin "autoimmunity prone," showing upregulation of many proinflammatory genes, even healthy women. We previously identified VGLL3 as a putative transcription cofactor enriched female skin. Here, we demonstrate that skin-directed overexpression murine causes severe lupus-like rash and systemic autoimmune involves B cell expansion, autoantibody production, immune complex deposition, end-organ...
Abstract Chronic macrophage inflammation is a hallmark of type 2 diabetes (T2D) and linked to the development secondary diabetic complications. T2D characterized by excess concentrations saturated fatty acids (SFA) that activate innate immune inflammatory responses, however, mechanism(s) which SFAs control unknown. Using monocyte‐macrophages isolated from human blood murine models, we demonstrate palmitate (C16:0), most abundant circulating SFA in T2D, increases expression histone...
Significance The COVID-19 pandemic has disproportionately affected patients with comorbidities, namely, obesity and type 2 diabetes. Macrophages (Mφs) are a key innate immune cell primarily responsible for the harmful, hyperinflammatory “cytokine storm” in that develop severe COVID-19. We describe mechanism this Mφ-mediated cytokine storm response to coronavirus. In coronavirus infection, expression of chromatin-modifying enzyme, SETDB2, decreases Mφs, leading increased transcription...
Macrophage (Mφ) plasticity is critical for normal wound repair; however, in type 2 diabetic wounds, Mφs persist a low-grade inflammatory state that prevents the resolution of inflammation. Increased NLRP3 inflammasome activity has been shown Mφs; molecular mechanisms regulating expression and are unclear. Here, we identified keratinocytes induce Nlrp3 gene through IL-1 receptor-mediated signaling, resulting enhanced activation presence pathogen-associated patterns damage-associated patterns....
A critical component of wound healing is the transition from inflammatory phase to proliferation initiate and remodeling wound. Macrophages are for initiation resolution during repair. In diabetes, macrophages display a sustained phenotype in late characterized by elevated production cytokines, such as TNF-α. Previous studies have shown that an altered epigenetic program directs diabetic toward proinflammatory phenotype, contributing phase. Males absent on first (MOF) histone...
Macrophages are critical for the initiation and resolution of inflammatory phase wound healing. In diabetes, macrophages display a prolonged phenotype preventing tissue repair. TLRs, particularly TLR4, have been shown to regulate myeloid-mediated inflammation in wounds. We examined isolated from wounds patients afflicted with diabetes healthy controls as well murine diabetic model demonstrating dynamic expression TLR4 results altered metabolic pathways macrophages. Further, using...
Long-standing hypertension (HTN) affects multiple organs and leads to pathologic arterial remodeling, which is driven by smooth muscle cell (SMC) plasticity. To identify relevant genes regulating SMC function in HTN, we considered Genome Wide Association Studies (GWAS) of blood pressure, focusing on encoding epigenetic enzymes, control fate cardiovascular disease. Using statistical fine mapping the KDM6 (JMJD3) locus, found that rs62059712 most likely casual variant, with each major T allele...
Abstract Systemic lupus erythematosus is an autoimmune disease characterized by increased type I IFNs, autoantibodies, and inflammatory-mediated multiorgan damage. TLR7 activation important contributor to systemic pathogenesis, but the mechanisms which IFNs participate in TLR7-driven pathologic conditions remain uncertain. In this study, we examined requirement for TLR7-stimulated nephritis. Lupus-prone NZM2328, INZM (which lack a functional IFN receptor), NZM2328 IL-1β−/− mice were treated...
Wound repair following acute injury requires a coordinated inflammatory response. Type I IFN signaling is important for regulating the response after skin injury. IFN-κ, type IFN, has recently been found to drive inflammation in lupus and psoriasis; however, role of IFN-κ context normal or dysregulated wound healing unclear. Here, we show that Ifnk expression upregulated keratinocytes early essential tissue repair. Under diabetic conditions, was decreased keratinocytes, impaired....
Plasmacytoid dendritic cells (pDCs) are first responders to tissue injury, where they prime naive T cells. The role of pDCs in physiologic wound repair has been examined, but little is known about diabetic and their interactions with CD4+ Diabetic wounds characterized by increased levels inflammatory IL-17A cytokine, partly due Th17 This excess, impairs repair. Here, using human murine healing models, we found that produced excess IL-6 TGF-β these cytokines skewed toward a phenotype...
Immune cell mediated inflammation is important in normal tissue regeneration but can be pathologic diabetic wounds. Limited literature exists on the role of CD4+T cells or wound repair, however, imbalance CD4+TH17/Treg has been found to promote other tissues. Here, using human and murine transgenic models, we identified that histone methyltransferase MLL1 directly regulates TH17 transcription factor RORγ via an H3K4me3 mechanism increases expression Notch receptors downstream signaling....
Abstract Diabetic keratinocytes display an overexpression of chemokines that contribute to prolonged inflammation and non-healing. Using sequencing, we identified Th17 cells IL-17A signature predominate in human diabetic wound tissue compared non-diabetic controls. The effects increased skin on keratinocyte function is unknown. We subjected isolated murine a 5hr rIL-17A stimulation performed bulk RNA-seq. observed neutrophil chemoattract genes Cxcl1, Cxcl3, Cxcl5 their analyzed epigenetic...
Macrophage transition from an inflammatory to reparative phenotype after tissue injury is controlled by epigenetic enzymes that regulate gene expression. We have previously identified the histone methyltransferase SETDB2 in macrophages drives repair repressing NF-κB-mediated inflammation. Complementary ATAC-Seq and RNA-Seq of wound isolated mice deficient myeloid cells revealed suppresses program inhibiting chromatin accessibility at NF-κB-dependent promoters. found STAT3 was required for...
<p dir="ltr"><b>Abstract</b></p><p dir="ltr">Macrophage (Mφ) plasticity is critical for normal wound repair; however, in type 2 diabetic wounds, Mφs persist a low-grade inflammatory state that prevents the resolution of inflammation. Increased NLRP3 inflammasome activity has been shown Mφs; molecular mechanisms regulating expression and are unclear. Here, we identified keratinocytes induce <i>Nlrp3 </i>gene through IL-1 receptor-mediated signaling,...
<p dir="ltr"><b>Abstract</b></p><p dir="ltr">Macrophage (Mφ) plasticity is critical for normal wound repair; however, in type 2 diabetic wounds, Mφs persist a low-grade inflammatory state that prevents the resolution of inflammation. Increased NLRP3 inflammasome activity has been shown Mφs; molecular mechanisms regulating expression and are unclear. Here, we identified keratinocytes induce <i>Nlrp3 </i>gene through IL-1 receptor-mediated signaling,...