A5036669790- Sirtuins and Resveratrol in Medicine
- Mitochondrial Function and Pathology
- Calcium signaling and nucleotide metabolism
- Diet and metabolism studies
- PARP inhibition in cancer therapy
- Tryptophan and brain disorders
- Autophagy in Disease and Therapy
- Genetics, Aging, and Longevity in Model Organisms
- Eating Disorders and Behaviors
- Fatty Acid Research and Health
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Adenosine and Purinergic Signaling
- RNA modifications and cancer
- Gut microbiota and health
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- MicroRNA in disease regulation
- Organ Transplantation Techniques and Outcomes
- NF-κB Signaling Pathways
- Pancreatic and Hepatic Oncology Research
- interferon and immune responses
- Helicobacter pylori-related gastroenterology studies
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
California University of Pennsylvania
2020-2024
University of Pennsylvania
2016-2023
University of California, Riverside
2007-2016
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...
The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma toxins. During regeneration, concentration nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition precursors. To test whether NAD availability restricts rate we supplied riboside (NR), an precursor, drinking water mice subjected partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration regenerating livers....
The obesity epidemic in the U.S. has led to extensive research into potential contributing dietary factors, especially fat and fructose. Recently, increased consumption of soybean oil, which is rich polyunsaturated fatty acids (PUFAs), been proposed play a causal role epidemic. Here, we designed series four isocaloric diets (HFD, SO-HFD, F-HFD, F-SO-HFD) investigate effects saturated versus unsaturated fat, as well fructose, on diabetes. C57/BL6 male mice fed diet moderately high from...
HNF4α has been implicated in colitis and colon cancer humans but the role of different isoforms expressed from two promoters (P1 P2) active is not clear. Here, we show that P1-HNF4α primarily differentiated compartment mouse colonic crypt P2-HNF4α proliferative compartment. Exon swap mice express only P1- or have gene expression profiles, interacting proteins, cellular migration, ion transport epithelial barrier function. The also exhibit altered susceptibilities to experimental (DSS)...
The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved protein kinase that regulates growth and metabolism. mTOR found in two complexes, mTORC1 mTORC2, have distinct components substrates are both inhibited by rapamycin, a macrolide drug robustly extends lifespan multiple species including worms mice. Although the beneficial effect on longevity generally attributed to reduced signaling, disruption mTORC2 signaling can also influence worms, either positively or negatively...
Abstract Nuclear receptors (NRs) are a superfamily of transcription factors whose genomic functions known to be activated by lipophilic ligands, but little is about how deactivate them or turn on their nongenomic functions. One obvious mechanism alter the nuclear localization receptors. Here, we show that protein kinase C (PKC) phosphorylates highly conserved serine (Ser) between two zinc fingers DNA binding domain orphan receptor hepatocyte factor 4α (HNF4α). This Ser (S78) adjacent several...
Src tyrosine kinase has long been implicated in colon cancer but much remains to be learned about its substrates. The nuclear receptor hepatocyte factor 4α (HNF4α) just recently role is poorly defined. Here we show that c-Src phosphorylates human HNF4α on three tyrosines an interdependent and isoform-specific fashion. initial phosphorylation site a Tyr residue (Y14) present the N-terminal A/B domain of P1- not P2-driven HNF4α. Phospho-Y14 interacts with SH2 domain, leading two additional...
The nuclear receptor hepatocyte factor 4α (HNF4α) is tumor suppressive in the liver but amplified colon cancer, suggesting that it also might be oncogenic. To investigate whether this discrepancy due to different HNF4α isoforms derived from its two promoters (P1 and P2), we generated Tet-On-inducible human cancer (HCT116) cell lines express either P1-driven (HNF4α2) or P2-driven (HNF4α8) isoform analyzed them for growth global changes gene expression (transcriptome sequencing [RNA-seq]...
SUMMARY Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family defensive deacylases. During aging, levels NAD + can decrease by up to 50% some tissues, repletion which provides range health benefits both mice humans. Whether or not precursor nicotinamide mononucleotide (NMN) extends lifespan mammals known. Here we investigate effect long-term administration NMN on...
Abstract The prevalence of obesity increases with age in humans and rodents. Age‐related is characterized by leptin resistance associated heightened risk metabolic disorders. However, the effect per se has been difficult to disentangle from other effects aging. Here we demonstrate that celastrol, a natural phytochemical was previously shown act as sensitizer, induces weight loss aged animals, but not young controls. Celastrol reduces food intake lowers fasting glucose without affecting...
Rapamycin delays multiple age-related conditions and extends lifespan in organisms ranging from yeast to mice. However, the mechanisms by which rapamycin influences longevity are incompletely understood. The objective of this study was investigate effect on NAD+/NADH redox balance. We report that ratio C2C12 myoblasts or differentiated myotubes significantly decreases over time culture, prevents effect. Despite lowering NADH available support ATP generation, increases availability,...
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 Background Alu repeats, which account for ~10% of the human genome, were originally considered to be junk DNA. Recent studies, however, suggest that they may contain transcription factor binding sites and hence possibly play a role in regulating gene expression. Results Here, we show highly conserved member nuclear receptor superfamily ligand-dependent factors, hepatocyte 4alpha (HNF4α, NR2A1), are prevalent repeats. We employ high throughput protein microarrays (PBMs) HNF4α binds...