A5050063788- Sirtuins and Resveratrol in Medicine
- Virus-based gene therapy research
- Lysosomal Storage Disorders Research
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Viral Infections and Immunology Research
- Circadian rhythm and melatonin
- RNA Interference and Gene Delivery
- Biochemical effects in animals
- CAR-T cell therapy research
- Light effects on plants
- Calcium signaling and nucleotide metabolism
- ATP Synthase and ATPases Research
- Plant Molecular Biology Research
- Genetics and Neurodevelopmental Disorders
- MicroRNA in disease regulation
- Biochemical and Molecular Research
- Nerve injury and regeneration
- Cell death mechanisms and regulation
- Adrenal and Paraganglionic Tumors
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Glycogen Storage Diseases and Myoclonus
- Histone Deacetylase Inhibitors Research
- Genomics, phytochemicals, and oxidative stress
Spark Therapeutics (United States)
2019-2021
University of Pennsylvania
2002-2017
Harvard University
2007-2013
Cancer Research Institute
2002-2005
UPMC Hillman Cancer Center
2002-2003
It's a SIRT Intense attention has focused on the SIRT1 deacetylase as possible target for anti-aging drugs. But unexpected complications in assays of activity have made it unclear whether compounds thought to be sirtuin-activating (STACs) are really direct regulators enzyme. Further exploration these effects by Hubbard et al. (p. 1216 ; see Perspective Yuan and Marmorstein ) revealed that interaction with certain substrates allows activation STACs identified critical amino acids required...
Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, a transcription factor (TF) that functions both core repressive component of the cell-autonomous clock regulator genes. Here, we show Rev-erbα modulates metabolism different genomic mechanisms. Clock control requires to bind directly genome at its cognate sites, where it competes with activating ROR TFs. By contrast, regulates genes primarily recruiting HDAC3 co-repressor sites which is tethered cell...
The formation of myelin by Schwann cells (SCs) occurs via a series orchestrated molecular events. We previously used global expression profiling to examine peripheral nerve myelination and identified the NAD + -dependent deacetylase Sir-two-homolog 2 (Sirt2) as protein likely be involved in myelination. Here, we show that Sirt2 SCs is correlated with structural components during both developmental remyelination after injury. Transgenic mice lacking or overexpressing specifically delays...
Resveratrol isa plant-derived polyphenol that promotes health and disease resistance inrodent models, extends lifespan in lower organisms. A major challengeis to understand the biological processes molecular pathways by whichresveratrol induces these beneficial effects. Autophagy is a criticalprocess which cells turn over damaged components maintain bioenergeticrequirements. Disruption of normal balance between pro- andanti-autophagic signals linked cancer, liver disease,...
The KEAP1-NRF2 pathway is the principal protective response to oxidative and electrophilic stresses. Under homeostatic conditions, KEAP1 forms part of an E3 ubiquitin ligase, which tightly regulates activity transcription factor NRF2 by ...
The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion leads to fatty liver. To elucidate the underlying mechanism, here we report method cross-linking followed by mass spectrometry define high-confidence interactome in vivo that includes canonical NCoR-HDAC3 complex as well Prospero-related homeobox 1 protein (PROX1). PROX1 co-localize extensively on mouse liver genome, are co-recruited hepatocyte nuclear factor 4α (HNF4α). HDAC3-PROX1...
The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers tight balance between cellular events that consume ATP and the rate production. However, after growth factor withdrawal, declines. To investigate these changes, mitochondria from factor-deprived isolated before onset apoptosis were characterized in vitro . Mitochondria have lost their undergo matrix condensation response ADP, which is accompanied by failure perform ADP-coupled respiration. At time analysis,...
Abstract Pompe disease (PD) is a severe neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). PD currently treated with replacement therapy (ERT) intravenous infusions recombinant human GAA (rhGAA). Although introduction ERT represents breakthrough in management PD, approach suffers from several shortcomings. Here, we developed mouse model to compare efficacy hepatic gene transfer adeno-associated virus (AAV) vectors expressing secretable long-term...
SIRT1 is an NAD (+) -dependent deacetylase that counteracts multiple disease states associated with aging and may underlie some of the health benefits calorie restriction. Understanding how regulated in vivo could therefore lead to new strategies treat age-related diseases. forms a stable complex DBC1, endogenous inhibitor. Little known regarding biochemical nature SIRT1-DBC1 formation, it whether or not possible block this interaction pharmacologically. In study, we show critical residues...
Extensive clinical data from liver-mediated gene therapy trials have shown that dose-dependent immune responses against the vector capsid may impair or even preclude transgene expression if not managed successfully with prompt suppression. The goal of this preclinical study was to generate an adeno-associated viral (AAV) capable expressing therapeutic levels B-domain deleted factor VIII (FVIII) at lowest possible dose minimize potential Risk a capsid-mediated response in setting. Here, we...