A5101760849- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Venous Thromboembolism Diagnosis and Management
- Endoplasmic Reticulum Stress and Disease
- Cardiac Arrest and Resuscitation
- RNA Research and Splicing
- Protein Kinase Regulation and GTPase Signaling
- Acute Ischemic Stroke Management
- Dialysis and Renal Disease Management
- Sepsis Diagnosis and Treatment
- Cardiac electrophysiology and arrhythmias
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Acute Myocardial Infarction Research
- Acute Kidney Injury Research
- 14-3-3 protein interactions
- Microtubule and mitosis dynamics
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Nutrition, Genetics, and Disease
- Digital Imaging for Blood Diseases
- Respiratory and Cough-Related Research
- Adenosine and Purinergic Signaling
- Asthma and respiratory diseases
- Cholesterol and Lipid Metabolism
Icahn School of Medicine at Mount Sinai
2024-2025
Mount Sinai Beth Israel
2023-2024
Mount Sinai Health System
2024
Model Animal Research Center
2012-2022
Nanjing University
2012-2022
Nanjing Drum Tower Hospital
2018-2022
Brooklyn Hospital Center
2022
State Key Laboratory of Pharmaceutical Biotechnology
2015-2019
University of Dundee
2008-2010
Capital Institute of Pediatrics
2003
Abstract Background The global use of kidney replacement therapy (KRT) has increased, mirroring the incidence acute injury and chronic disease. Despite its growing clinical usage, patient outcomes with KRT modalities remain controversial. In this meta-analysis, we sought to compare mortality patients any disease requiring peritoneal dialysis (PD), hemodialysis (HD), or continuous renal (CRRT). Methods investigation was conducted according Preferred Reporting Items for Systematic Reviews...
AS160 (Akt substrate of 160 kDa) is a Rab GTPase-activating protein implicated in insulin control GLUT4 (glucose transporter 4) trafficking. In humans, truncation mutation (R363X) one allele decreased the expression and caused severe postprandial hyperinsulinaemia during puberty. To complement limited studies possible we generated an AS160-knockout mouse. wild-type mice, relatively high adipose tissue soleus muscle, low EDL (extensor digitorum longus) muscle detectable liver only after...
Significance Excess energy intake and physical inactivity are two major factors causing obesity, but the underlying mechanisms have not been fully understood. Both excess increase cellular status that is monitored by energy-sensing AMP-activated protein kinase (AMPK). We demonstrate AMPK–tre-2/USP6, BUB2, cdc16 domain family member 1 (the TBC GTPase activating domain) (TBC1D1) signaling nexus regulates insulin-like growth factor (IGF1) secretion. Disruption of this AMPK–TBC1D1 in mice...
SPEG (Striated muscle preferentially expressed protein kinase) has 2 kinase-domains and is critical for cardiac development function. However, it not clear how these function to maintain performance.To determine the molecular functions of SPEG.A proteomics approach identified SERCA2a (sarcoplasmic/endoplasmic reticulum calcium ATPase 2a) as a interacting with second kinase-domain but first SPEG. Furthermore, could phosphorylate Thr484 on SERCA2a, promote its oligomerization increase reuptake...
Abstract Diabetic cardiomyopathy is a progressive disease in diabetic patients, and myocardial insulin resistance contributes to its pathogenesis through incompletely-defined mechanisms. Striated muscle preferentially expressed protein kinase (SPEG) has two kinase-domains critical cardiac regulator. Here we show that SPEG phosphorylated on Ser 2461 /Ser 2462 /Thr 2463 by B (PKB) response insulin. PKB-mediated phosphorylation of activates second kinase-domain, which turn phosphorylates...
The AS160 (Akt substrate of 160 kDa) is a Rab-GTPase activating protein (RabGAP) with several other functional domains, and its deficiency in mice or human patients lowers GLUT4 levels causes severe insulin resistance. How diminished proteins remains unknown. We found that the deletion decreased cell/tissue-autonomous manner. Consequently, skeletal muscle–specific caused postprandial hyperglycemia hyperinsulinemia. pathogenic effects are mainly, if not exclusively, due to loss RabGAP...
Nonalcoholic fatty liver disease (NAFLD) affects approximately a quarter of the population worldwide, and persistent overnutrition is one major causes. However, underlying molecular basis has not been fully elucidated, no specific drug approved for this disease. Here, we identify regulatory mechanism that reveals novel function Rab2A in progression NAFLD based on energy status PPARγ. The mechanistic analysis shows nutrition repletion suppresses phosphorylation AMPK-TBC1D1 signaling, augments...
AS160 and its closely related protein TBC1D1 have emerged as key mediators for both insulin- contraction-stimulated muscle glucose uptake through regulating GLUT4 trafficking. Insulin increases phosphorylation at multiple Akt/PKB consensus sites, including Thr(649), promotes binding to 14-3-3 proteins phospho-Thr(649). We recently provided genetic evidence that AS160-Thr(649) phosphorylation/14-3-3 plays a role in mediating insulin-stimulated muscle. Contraction has also been proposed...
Abstract The study aimed to evaluate the prevalence, risk factors, and clinical outcomes of pulmonary embolism in patients diagnosed with sepsis without shock. National Inpatient Sample was used identify adults shock between 2017 2019. prevalence acute association in-hospital mortality, hospital length stay for survivors, overall costs hospitalization were evaluated. Multivariable logistic linear regression analyses, adjusted various parameters, explore these associations. Of estimated...
Skeletal muscle absorbs long-chain fatty acids (LCFAs) that are either oxidized in mitochondria or temporarily stored as triglycerides lipid droplets (LDs). So far, it is still not fully understood how uptake and storage regulated whether these important for whole-body homeostasis. Here we show the small GTPase Rab8a regulates skeletal muscle. Muscle-specific deletion caused hyperlipidemia exacerbated hepatosteatosis induced by a high-fat diet. Mechanistically, deficiency decreased LCFA...
The RalGAPα1/β complex links insulin signaling to glucose and lipid metabolism in skeletal muscle through RalA activation.
ABSTRACT The low-density lipoprotein receptor (LDLR) plays a critical role in the liver for clearance of plasma (LDL). Its deficiency causes hypercholesterolemia many models. To facilitate usage rats as animal models discovery cholesterol-lowering drugs, we took genetic approach to delete LDLR aiming increase LDL cholesterol (LDL-C). An knockout rat was generated via zinc-finger nuclease technology, which harbors 19-basepair deletion seventh exon ldlr gene. As expected, elevated total and...
Superoxide dismutase (SOD) is an attractive therapeutic agent to ameliorate oxidative stress that critical for the initiation and progression of inflammatory bowel disease (IBD). However, short life SOD limits its clinical application. In this study, we aim examine effects a hyperthermostable from Thermus thermophilus HB27 (TtSOD) treatment experimentally induced IBD.A recombinant TtSOD was expressed purified Escherichia coli, were examined in 2 experimental IBD animal models.In by...
CudA, a nuclear protein required for Dictyostelium prespore-specific gene expression, binds in vivo to the promoter of cotC prespore gene. A 14 nucleotide region CudA vitro and ECudA, an Entamoeba homologue, also this site. The ECudA DNA-binding sites contain dyad and, consistent with symmetrical binding site, forms homodimer yeast two-hybrid system. Mutation within reduces expression from cells. proteins share 120 amino acid core homology, clustered point mutations introduced into two...
Abstract Background Management of PE has become streamlined with the implementation Response Teams (PERT). Race, ethnicity and insurance status are known to influence outcomes patients acute PE. However, whether PERT-based care mitigates these racial ethnic disparities remains unknown. Our aim was assess association race, for managed by PERT. Methods We performed a retrospective chart review 290 PE, who were admitted one three urban teaching hospitals in Mount Sinai Health System (New York,...
The insulin-like growth factor 1 (IGF1) pathway has been linked with various diseases including diabetes, cancer and aging. In contrast to the well-established regulatory mechanisms controlling IGF1 expression, molecular regulating its secretion are not fully understood. AMP-activated protein kinase (AMPK) is a key energy sensor, cumulative evidence shows that it an attractive therapeutic target for treatment of Here we found deficiency AMPK promoted in mouse primary hepatocytes....
The Rab GTPase activating protein (RabGAP), AS160/TBC1D4, is an important substrate of kinase B (PKB), and regulates insulin-stimulated trafficking glucose transporter 4. Besides, AS160/TBC1D4 has also been shown to regulate many other membrane proteins including FA translocase/CD36 in cardiomyocytes. However, it not clear whether plays any role regulating heart functions vivo. Here, we found that PKB-mediated phosphorylation Thr649 on represented one the major PAS-binding signals response...