A5074058117- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Adipose Tissue and Metabolism
- Sirtuins and Resveratrol in Medicine
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- PARP inhibition in cancer therapy
- Cholesterol and Lipid Metabolism
- Diet, Metabolism, and Disease
- PI3K/AKT/mTOR signaling in cancer
- CRISPR and Genetic Engineering
- Lipid metabolism and biosynthesis
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Liver Disease Diagnosis and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- RNA modifications and cancer
- Protein Kinase Regulation and GTPase Signaling
- Organ Transplantation Techniques and Outcomes
Yale University
2018-2025
University of Pennsylvania
2018-2021
VA Connecticut Research and Education Foundation
2018
Mitochondrial NAD levels influence fuel selection, circadian rhythms, and cell survival under stress. It has alternately been argued that in mammalian mitochondria arises from import of cytosolic nicotinamide (NAM), mononucleotide (NMN), or itself. We provide evidence murine human take up intact NAD. Isolated preparations cannot make NAM, while is synthesized NMN, it does not localize to the mitochondrial matrix effectively support oxidative phosphorylation. Treating cells with riboside...
Liver regeneration is critical to survival after traumatic injuries, exposure hepatotoxins, or surgical interventions, yet the underlying signaling and metabolic pathways remain unclear. In this study, we show that hepatocyte-specific loss of mitochondrial deacetylase SIRT3 drastically impairs worsens function partial hepatectomy. Sirtuins, including SIRT3, require NAD as a cosubstrate. We previously showed precursor nicotinamide riboside (NR) promotes liver regeneration, but whether...
Pharmacological agents targeting the mTOR complexes are used clinically as immunosuppressants and anticancer can extend lifespan of model organisms. An undesirable side effect these drugs is hyperlipidemia. Although multiple roles have been described for complex 1 (mTORC1) in lipid metabolism, etiology hyperlipidemia remains incompletely understood. The objective this study was to determine influence adipocyte mTORC1 signaling systemic homeostasis vivo. We characterized metabolism mice...
Abstract The increased hepatic gluconeogenesis in type 2 diabetes mellitus has often been ascribed to transcription of phosphoenolpyruvate carboxykinase 1, cystolic form (PEPCK1), although recent evidence questioned this attribution. To assess the metabolic role PEPCK1, we treated regular chow fed and high-fat (HFF) male Sprague-Dawley rats with a 2′-O-methoxyethyl chimeric antisense oligonucleotide (ASO) against PEPCK1 compared them control ASO-treated rats. ASO effectively decreased...
Hepatic insulin resistance (IR) is often said to be "pathway-selective" with preserved stimulation of
Rapamycin, a fungicidal macrolide, has been shown to increase life span and delay the onset of age related diseases across several model organisms. However, rapamycin treatment leads metabolic dysregulation including glucose intolerance hyperlipidemia, which limits its potential utility as an anti‐ageing agent. Rapamycin increases serum triglycerides in human patients by 95%, while it influences expression multiple proteins involved lipid handling liver adipose tissue, precise mechanism...