Risheng Ye

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Neurodegenerative diseases are often associated with dysfunction in protein quality control. The endoplasmic reticulum (ER), a key site for protein synthesis, senses stressful conditions by activating the unfolded protein response (UPR). In this study we report the creation of a novel mouse model in which GRP78/BiP, a major ER chaperone and master regulator(More)
The unfolded protein response (UPR) is an evolutionarily conserved mechanism that activates both proapoptotic and survival pathways to allow eukaryotic cells to adapt to endoplasmic reticulum (ER) stress. Although the UPR has been implicated in tumorigenesis, its precise role in endogenous cancer remains unclear. A major UPR protective response is the(More)
Glucose-regulated protein 78 (GRP78)/BiP is a multifunctional protein which plays a major role in endoplasmic reticulum (ER) protein processing, protein quality control, maintaining ER homeostasis, and controlling cell signaling and viability. Previously, using a transgene-induced mammary tumor model, we showed that Grp78 heterozygosity impeded cancer(More)
OBJECTIVE To investigate the role of the endoplasmic reticulum (ER) chaperone glucose-regulated protein (GRP) 78/BiP in the pathogenesis of obesity, insulin resistance, and type 2 diabetes. RESEARCH DESIGN AND METHODS Male Grp78(+/-) mice and their wild-type littermates were subjected to a high-fat diet (HFD) regimen. Pathogenesis of obesity and type 2(More)
As an adipokine in circulation, adiponectin has been extensively studied for its beneficial metabolic effects. While many important functions have been attributed to adiponectin under high-fat diet conditions, little is known about its essential role under regular chow. Employing a mouse model with inducible, acute β-cell ablation, we uncovered an essential(More)
Elevated levels of TGFb are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFb pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFb remains challenging because TGFb has tumor suppressor functions in many epithelial malignancies, including pancreatic(More)
Pathological expansion of adipose tissue contributes to the metabolic syndrome. Distinct depots develop at various times under different physiological conditions. The transcriptional cascade mediating adipogenesis is established in vitro, and centres around a core program involving PPARγ and C/EBPα. We developed an inducible, adipocyte-specific knockout(More)
BACKGROUND The selective estrogen receptor modulator tamoxifen, in combination with the Cre-ER(T2) fusion protein, has been one of the mainstream methods to induce genetic recombination and has found widespread application in lineage tracing studies. METHODS & RESULTS Here, we report that tamoxifen exposure at widely used concentrations remains detectable(More)
BACKGROUND Evidence hints at the ability of β-cells to emerge from non-β-cells upon genetic or pharmacological interventions. However, their quantitative contributions to the process of autonomous β-cell regeneration without genetic or pharmacological manipulations remain to be determined. METHODS & RESULTS Using PANIC-ATTAC mice, a model of titratable,(More)
As an early hallmark of type 2 diabetes, the associated insulin resistance in peripheral tissues demands extra insulin production from the pancreatic b cells. Circulating glucose has long been recognized as the primary messenger, triggering acute and prolonged insulin secretion via well-defined biochemical pathways in b cells. However, additional mechanisms(More)