A5084868801- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Metabolism, Diabetes, and Cancer
- Bone Metabolism and Diseases
- Diabetes and associated disorders
- Diet, Metabolism, and Disease
- NF-κB Signaling Pathways
- Immune Cell Function and Interaction
- Digestive system and related health
- Pancreatitis Pathology and Treatment
- Diabetes Management and Research
- Signaling Pathways in Disease
- Advanced Breast Cancer Therapies
- Cytokine Signaling Pathways and Interactions
- Curcumin's Biomedical Applications
- Cell death mechanisms and regulation
- Nutrition, Genetics, and Disease
- Neuroendocrine Tumor Research Advances
- Microbial Metabolites in Food Biotechnology
City of Hope
2020-2025
Icahn School of Medicine at Mount Sinai
2014-2023
Beckman Research Institute
2020-2021
New York Proton Center
2018
University of Pittsburgh
2010-2012
Virginia Tech
2010
OBJECTIVE Inducing human β-cell growth while enhancing function is a major goal in the treatment of diabetes. Parathyroid hormone–related protein (PTHrP) enhances rodent and through parathyroid hormone-1 receptor (PTH1R). Based on this, we hypothesized that PTH1R expressed β-cells PTHrP has potential to enhance proliferation and/or function. RESEARCH DESIGN AND METHODS expression, proliferation, glucose-stimulated insulin secretion (GSIS), expression differentiation cell-cycle genes were...
Loss of functional β-cell mass is a major cause diabetes. Thus, identifying regulators health crucial for treating this disease. The We evaluated Lgr4 expression in mouse and human islets response to acute (proinflammatory cytokines), or chronic (high fat fed mice, db/db aging) stress. To determine the role LGR4 we employed vitro loss gain function primary rodent β-cells examined its mechanism action INS1 cell line. Using was reduced by multiple stressors. In vitro, knockdown decreased...
Treatment for type 1 diabetes (T1D) requires stimulation of functional β cell regeneration and survival under stress. Previously, we showed that inhibition the RANKL/RANK [receptor activator nuclear factor kappa Β (NF-κB) ligand] pathway, by osteoprotegerin anti-osteoporotic drug denosumab, induces rodent human proliferation. We demonstrate RANK pathway mediates cytokine-induced death through RANK-TRAF6 interaction induction NF-κB activation. Osteoprotegerin denosumab protected cells against...
Aims/Hypothesis Finding ways to stimulate the regeneration of endogenous pancreatic beta cells is an important goal in treatment diabetes. Parathyroid hormone-related protein (PTHrP), full-length (1–139) and amino-terminal (1–36) peptides, enhance cell function, proliferation, survival. Therefore, we hypothesize that PTHrP(1–36) has potential regenerate cells. Methods The partial pancreatectomy (PPx) mouse model injury was used test this hypothesis. Male Balb/c mice underwent either...
Abstract Genetic deletion of cyclin-dependent kinase 4 (Cdk4) is associated with pancreatic beta cell loss and glucose dysregulation in rodents. Palbociclib, one the first selective CDK4/6 inhibitors approved for treatment advanced breast cancer, currently being investigated as an adjuvant patients early-stage cancer a variety cancers covering wide-range patient populations. Hence, longer chronic toxicity studies were necessary to further examine its safety profile. The effects different...
Diabetes occurs due to a loss of functional β-cells, resulting from β-cell death and dysfunction. Lactogens protect rodent human β-cells in vitro vivo against triggers cytotoxicity relevant diabetes, many which converge onto common pathway endoplasmic reticulum (ER) stress. However, whether lactogens modulate the ER stress is unknown. This study examines can mitigate diabetes incidence Akita (Ak) mice, model stress-induced akin neonatal humans. We show that INS-1 cells, primary two distinct...
Pancreatic β-cell stress contributes to diabetes progression. This study demonstrates that Leucine-rich repeat-containing G-protein-coupled-receptor-4 (LGR4) is critical for maintaining health and modulated by stressors. In vitro , Lgr4 knockdown decreases proliferation survival in rodent β-cells, while overexpression protects against cytokine-induced cell death human β-cells. Mechanistically, LGR4 suppresses Receptor Activator of Nuclear Factor Kappa B (NFκB) (RANK) its subsequent...
Non-digestible carbohydrates (NDC(4)) have been used as a low-calorie sweetener and prebiotics that stimulate the growth of certain intestinal bacteria support healthy colon conditions. In this study, we examined dietary effect commercially available NDCs on estrogen receptor positive (ER+) human breast cancer. We conducted feeding study fructooligosaccharides (FOSs), Fibersol 2 (F2; digestion resistant maltodextrin), Hi-Maize (HM; high amylose cornstarch), Frutafit (FF; range powdered...
ER stress is highly relevant in the context of diabetes, as inducers β cell death and dysfunction implicated disease - including proinflammatory cytokines glucolipotoxicity are known to impair function. Previous work has shown that prolactin (Prl) placental lactogen (PL), which bind same receptor (Prl-R), important for function proliferation, enhance survival against glucolipotoxicity. Here, we examine effect Prl/PL directly on associated unfolded protein response (UPR) cell. was induced...
Diabetes occurs due to a loss of functional β-cells, resulting from β-cell death and dysfunction. Lactogens protect rodent human β-cells <i>in vitro</i> and<i> in vivo</i> against triggers cytotoxicity relevant diabetes, many which converge onto common pathway, endoplasmic reticulum (ER) stress. However, whether lactogens modulate the ER stress pathway is unknown. This study examines if can mitigate diabetes incidence Akita mice, model stress-induced akin neonatal...
Diabetes occurs due to a loss of functional β-cells, resulting from β-cell death and dysfunction. Lactogens protect rodent human β-cells <i>in vitro</i> and<i> in vivo</i> against triggers cytotoxicity relevant diabetes, many which converge onto common pathway, endoplasmic reticulum (ER) stress. However, whether lactogens modulate the ER stress pathway is unknown. This study examines if can mitigate diabetes incidence Akita mice, model stress-induced akin neonatal...
Abstract Our lab has shown that RANK (Receptor activator of the NF-κB) by interacting with its ligand, RANKL, inhibits ß-cell proliferation and survival; which can be reversed Osteoprotegerin (OPG). Recently, G protein-coupled receptor LGR4 (leucine-rich repeat-containing 4), binds R-spondin (RSPO), was identified as a novel for RANKL in osteoclast precursor cells. Thus, bind two distinct receptors, osteoclasts, leading to opposite effects on osteoclastogenesis. is expressed rodent human...