A5090388742- Pancreatic and Hepatic Oncology Research
- Growth Hormone and Insulin-like Growth Factors
- Pancreatic function and diabetes
- FOXO transcription factor regulation
- Diabetes and associated disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Pancreatitis Pathology and Treatment
- Immune cells in cancer
- Diabetes Management and Research
- Phagocytosis and Immune Regulation
- Cancer, Lipids, and Metabolism
- Liver Disease Diagnosis and Treatment
- Advanced Breast Cancer Therapies
- Cytokine Signaling Pathways and Interactions
- Adipose Tissue and Metabolism
- Fibroblast Growth Factor Research
- Electrospun Nanofibers in Biomedical Applications
- Peroxisome Proliferator-Activated Receptors
- Liver physiology and pathology
- Calpain Protease Function and Regulation
- Metabolism, Diabetes, and Cancer
- Tissue Engineering and Regenerative Medicine
- Endoplasmic Reticulum Stress and Disease
Children's Hospital of Pittsburgh
2009-2023
University of Pittsburgh
2010-2019
Merrill (United States)
2015
University of Pittsburgh Medical Center
2014
At this time, the only definitive treatment of hepatic failure is liver transplantation. However, transplantation has been limited by severely supply human donor livers. Alternatively, a regenerative medicine approach recently proposed in rodents that describe production three-dimensional whole-organ scaffolds for assembly engineered complete organs. In present study, we decellularization porcine livers to generate constructs at scale can be clinically relevant. Adult ischemic were...
OBJECTIVE Macrophages play an important role in the pathogenesis of insulin resistance via production proinflammatory cytokines. Our goal is to decipher molecular linkage between cytokine and macrophages. RESEARCH DESIGN AND METHODS We determined profiles cultured macrophages identified interleukin (IL)-1β gene as a potential target FoxO1, key transcription factor that mediates action on expression. studied mechanism by which FoxO1 insulin-dependent regulation IL-1β expression correlated...
The generation of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β fuel acute phase response (APR). To maintain body homeostasis, increase inflammatory proteins is resolved by via presently unknown mechanisms. Hepatocyte growth factor (HGF) transcribed in to IL-6. Since IL-6 production promotes HGF induces APR, we posited that accumulating might be a likely candidate for quelling excess inflammation under non-pathological conditions. We sought assess role how it influences regulation...
Lymphocyte activation gene-3 (LAG-3) is an inhibitory receptor expressed by CD4+ T cells and tempers their homeostatic expansion. Because cell proliferation tightly coupled to bioenergetics, we investigate the role of LAG-3 in modulating naive metabolism. deficiency enhances metabolic profile elevating levels mitochondrial biogenesis. In vivo, blockade partially restores expansion phenotype wild-type Lag3-/- cells, solidifying that controls these processes. also demonstrate greater signal...
Hepatic inflammation is culpable for the evolution of asymptomatic steatosis to nonalcoholic steatohepatitis (NASH). results from abnormal macrophage activation. We found that FoxO1 links overnutrition hepatic by regulating polarization and was upregulated in macrophages, correlating with inflammation, steatosis, fibrosis mice patients NASH. Myeloid cell conditional knockout skewed proinflammatory M1 antiinflammatory M2 phenotype, accompanied a reduction infiltration liver. These effects...
Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the profibrotic activity of tissue-resident macrophages in pancreatic cancer microenvironment. Here, we show that neoplastic epithelium, as well a subset macrophages, expresses prolactin-receptor (PRLR). High mobility group box 1-induced prolactin expression pancreas maintained FAK1 and STAT3 phosphorylation within epithelium stroma. Gain-of-function loss-of-function experiments...
Background The receptor for advanced glycation end-products (RAGE) has been suggested to modulate lung injury in models of acute pulmonary inflammation. To study this further, model systems utilizing wild type and RAGE knockout (KO) mice were used determine the role signaling lipopolysaccharide (LPS) E. coli induced effect intraperitoneal (i.p.) intratracheal (i.t.) administration mouse soluble on was also investigated. Methodology/Principal Findings C57BL/6 KO received an i.t. instillation...
Oxidative stress and persistent inflammation are exaggerated through chronic over-nutrition a sedentary lifestyle, resulting in insulin resistance. In type 2 diabetes (T2D), impaired signaling leads to hyperglycemia long-term complications, including metabolic liver dysfunction, non-alcoholic fatty disease (NAFLD). The manganese metalloporphyrin superoxide dismustase (SOD) mimetic, (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnP), is an oxidoreductase known scavenge reactive...
As a result of less than optimal outcomes the use islet allografts as standard insulin replacement therapy is limited to adults with history extreme glucose dysregulation and hypoglycemia unawareness. In this study, we examined prophylactic immunotherapy prevent allograft rejection in absence antirejection drugs. Our protocol achieve acceptance used negative vaccination strategy that comprised apoptotic donor cells delivered Incomplete Freund's Adjuvant (IFA) 1 week prior transplantation....
<p>The pancreas of adult prolactin deficient mice display no obvious abnormalities.</p>
Abstract In Type 1 Diabetes (T1D), CD4+ T cells drive autoimmune destruction of pancreatic β by activating M1 macrophages which hinders cell repair. Endogenous growth can occur if inflammation is tempered. A more controlled inflammatory response necessary to induce the regenerative process, characterized a transition macrophage phenotypes from M2. Macrophages NOD mice have several maturation defects. We hypothesize that upon in autoimmunity defective fail M2 phenotype, rendering unable...
<div>Abstract<p>Pancreatic ductal adenocarcinoma (PDAC) is associated with significant fibrosis. Recent findings have highlighted the profibrotic activity of tissue-resident macrophages in pancreatic cancer microenvironment. Here, we show that neoplastic epithelium, as well a subset macrophages, expresses prolactin-receptor (PRLR). High mobility group box 1–induced prolactin expression pancreas maintained FAK1 and STAT3 phosphorylation within epithelium stroma. Gain-of-function...
<p>Supplementary figure legends and methods.</p>
<p>Prolactin does not promote activation of Jak2 signaling pathway in BxPC3 cell line, which lacks PRLR expression.</p>
<p>Total FAK1 and STAT3 are present in KC;Prl-/- PanINs.</p>
<p>Prolactin does not promote activation of Jak2 signaling pathway in BxPC3 cell line, which lacks PRLR expression.</p>
<p>The pancreas of adult prolactin deficient mice display no obvious abnormalities.</p>
<p>Supplementary figure legends and methods.</p>