A5102898514- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Parasites and Host Interactions
- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- Reproductive System and Pregnancy
- Macrophage Migration Inhibitory Factor
- Eosinophilic Esophagitis
- Cell Adhesion Molecules Research
- Preterm Birth and Chorioamnionitis
- Immune Response and Inflammation
- Liver Disease Diagnosis and Treatment
- Diabetes and associated disorders
- Studies on Chitinases and Chitosanases
- Lipid metabolism and disorders
- Insect symbiosis and bacterial influences
- Cytokine Signaling Pathways and Interactions
- Respiratory and Cough-Related Research
- Cancer Immunotherapy and Biomarkers
- Chemokine receptors and signaling
- Adipokines, Inflammation, and Metabolic Diseases
- T-cell and B-cell Immunology
National Institutes of Health
2014-2018
National Institute of Allergy and Infectious Diseases
2014-2018
Dartmouth–Hitchcock Medical Center
2011
Dartmouth College
2009
Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In cross-sectional study of asthmatics varying severity (n = 51), endobronchial tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high TH17-high patterns were mutually exclusive in individual samples, their signatures inversely correlated differentially interleukin-13 (IL-13) IL-17A. To understand this dichotomous...
Combined blockade of TSLP, IL-25, and IL-33 may be needed to treat some forms progressive inflammation fibrosis.
Nonalcoholic fatty liver disease (NAFLD) is now the most common progressive in developed countries and second leading indication for transplantation due to extensive fibrosis it causes. NAFLD progression thought be tied chronic low-level type 1 inflammation originating adipose tissue during obesity; however, specific immunological mechanisms regulating of NAFLD-associated are unclear. To investigate immunopathogenesis more completely, we investigated dysfunction, nonalcoholic steatohepatitis...
Fibroproliferative diseases are driven by dysregulated tissue repair responses and a major cause of morbidity mortality because they affect nearly every organ system. Type 2 cytokine critically involved in repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis not well understood. Here, we have shown type effector interleukin-13 simultaneously, yet independently, directed hepatic compensatory proliferation hepatocytes biliary cells progressive...
Mice expressing a Cre recombinase from the lysozyme M-encoding locus (Lyz2) have been widely used to dissect gene function in macrophages and neutrophils. Here, we show that while naïve resident tissue IL-4Rαflox/deltaLysMCre mice almost completely lose IL-4Rα function, large fraction of elicited by sterile inflammatory stimuli, Schistosoma mansoni eggs, or S. infection, fail excise Il4rα. These F4/80hiCD11bhi macrophages, contrast express lower levels Lyz2 explaining why this population...
Elevated levels of IL-10 in the microenvironment human ovarian cancer and murine models are well established correlate with poor clinical prognosis. However, amongst a myriad immunosuppressive factors, actual contribution to tumor microenvironment, mechanisms by which it acts, its possible functional redundancy unknown. We previously demonstrated that elimination myeloid-derived suppressor cell (MDSC) compartment within ascites inhibited progression and, intriguingly, significantly decreased...
Persistent or dysregulated IL-13 responses are key drivers of fibrosis in multiple organ systems, and this identifies cytokine as an important therapeutic target. Nevertheless, the mechanisms by which blockade leads to amelioration remain unclear. Because IFN-γ exhibits potent anti-fibrotic activity, IL-4Rα signalling antagonizes effector function, compensatory increases activity following IL-13/IL-4Rα might contribute reduction fibrosis. To investigate role IFN-γ, we developed novel...
Ovarian tumor progression is marked by the peritoneal accumulation of leukocytes. Among these leukocytes, an immunosuppressive CD11b+CD11c+ population has been identified in both human and ovarian tumors. The use transplantable models murine tumors demonstrated that this promotes growth, whereas elimination shown to inhibit progression. Despite importance cells progression, mechanisms which are recruited largely unknown. Therefore, study analyzes migrate peritoneum with goal therapeutically...
Abstract Fibroproliferative diseases affect a significant proportion of the world's population. Despite this, core mechanisms driving organ fibrosis diverse etiologies remain ill defined. Recent studies suggest that integrin‐alpha V serves as master driver in multiple organs. Although contribute to progression fibrosis, TGF‐β and IL‐13 have emerged central mediators during type 1/type 17, 2 polarized inflammatory responses, respectively. To investigate if interactions or signaling is...
The ovarian cancer microenvironment recruits an array of immune cells to the site tumor growth. Within peritoneal ascites both humans and mice, predominant population tumor-infiltrating leukocytes is a CD11c(+)CD11b(+) variably referred as vascular (VLCs), tumor-associated macrophages, immature dendritic cells. We have previously shown that these are critical for growth because their selective elimination from inhibited progression. However, underlying mechanism by which this therapy was...
In our recently published report in Science Translational Medicine (1), we provided evidence of mutually exclusive regulation Th2 and Th17 inflammation bronchial biopsies obtained from asthmatic patients explored these mechanisms mouse models.