A5102825259- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Platelet Disorders and Treatments
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Cellular transport and secretion
- RNA Interference and Gene Delivery
- Bioinformatics and Genomic Networks
- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- Amino Acid Enzymes and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Blood groups and transfusion
- Extracellular vesicles in disease
- Polyamine Metabolism and Applications
- ATP Synthase and ATPases Research
- Congenital Anomalies and Fetal Surgery
- Gene Regulatory Network Analysis
- Cell Adhesion Molecules Research
- Hypothalamic control of reproductive hormones
- Diet and metabolism studies
- Cancer-related gene regulation
The University of Texas Southwestern Medical Center
2024
Children's Medical Center
2024
Southwestern Medical Center
2024
Royal North Shore Hospital
2011-2022
The University of Sydney
2011-2021
Howard Hughes Medical Institute
2014-2020
Massachusetts Institute of Technology
2013-2020
Boston Children's Hospital
2018-2020
Whitehead Institute for Biomedical Research
2011-2020
Broad Institute
2014-2020
The mTOR complex 1 (mTORC1) pathway promotes cell growth in response to many cues, including amino acids, which act through the Rag guanosine triphosphatases (GTPases) promote mTORC1 translocation lysosomal surface, its site of activation. Although progress has been made identifying positive regulators Rags, it is unknown if negative factors also exist. Here, we identify GATOR as a that interacts with Rags and composed two subcomplexes call GATOR1 -2. Inhibition subunits (DEPDC5, Nprl2,...
Stem cells can sort mitochondria by age The renewal of tissues in aging organisms requires stem cells, which have the unusual ability to divide asymmetrically into one daughter cell that retains properties and another differentiates a particular tissue type. Katajisto et al. used photoactivated marker proteins monitor organelles stemlike from human breast their distribution cells. Most were evenly distributed, but maintained stem-cell received more newly produced fewer old ones. Science ,...
Estrogen receptor alpha (ERalpha) plays a pivotal role in the regulation of food intake and energy expenditure by estrogens. Although it is well documented that disruption ERalpha signaling knockout (ERKO) mice leads to an obese phenotype, sites estrogen action mechanisms underlying this phenomenon are still largely unknown. In present study, we exploited RNA interference mediated adeno-associated viral vectors achieve focused silencing ventromedial nucleus hypothalamus, key center...
Development of biofluid-based molecular diagnostic tests for cancer is an important step towards tumor characterization and real-time monitoring in a minimally invasive fashion. Extracellular vesicles (EVs) are released from cells into body fluids can provide powerful platform biomarkers because they carry proteins nucleic acids. Detecting rare point mutations the background wild-type sequences biofluids such as blood cerebrospinal fluid (CSF) remains major challenge. Techniques BEAMing...
Estrogen receptor alpha (ERalpha) plays a major role in the regulation of neuroendocrine functions and behaviors by estrogens. Although generation ERalpha knockout mice advanced our knowledge functions, gene deletion using this method is global potentially confounded developmental consequences. To achieve site-specific knockdown normally developed adult brain, we have generated an adeno-associated virus vector expressing small hairpin RNA targeting ERalpha. After bilateral injection into...
α-Synuclein (α-Syn) is a key protein that accumulates as hyperphosphorylated aggregates in pathologic hallmark features of Parkinson's disease (PD) and other neurodegenerative disorders. Phosphorylation this at serine 129 believed to promote its aggregation neurotoxicity, suggesting post-translational modification could be therapeutic target. Here, we demonstrate phosphoprotein phosphatase 2A (PP2A) dephosphorylates α-Syn activity greatly enhanced by carboxyl methylation the catalytic C...
Mitochondria are metabolic organelles that essential for mammalian life, but the dynamics of mitochondrial metabolism within tissues in vivo remains incompletely understood. While whole-tissue metabolite profiling has been useful studying vivo, such an approach lacks resolution at cellular and subcellular level. In methods interrogating organellar metabolites specific cell types have limited. To address this, we built on prior work which exploited a mitochondrially localized 3XHA epitope tag...
Mitochondrial respiratory chain disorders are characterized by loss of electron transport (ETC) activity. Although the causes many such diseases known, there is a lack effective therapies. To identify genes that confer resistance to severe ETC dysfunction when inactivated, we performed genome-wide genetic screen in haploid human cells with mitochondrial complex III inhibitor antimycin. This revealed ATPIF1 strongly protects against antimycin-induced and cell death allowing for maintenance...
Peroxisomes are metabolic organelles that perform a diverse array of critical functions in human physiology. Traditional isolation methods for peroxisomes can take more than 1 h to complete and be laborious implement. To address this, we have now extended our prior work on rapid organellar via the development peroxisomally localized 3XHA epitope tag ("PEROXO-Tag") associated immunoprecipitation ("PEROXO-IP") workflow. Our PEROXO-IP workflow has excellent reproducibility, is easy implement,...
Abstract ATP synthesis and thermogenesis are two critical outputs of mitochondrial respiration. How these regulated to balance the cellular requirement for energy heat is largely unknown. Here we show that major facilitator superfamily domain containing 7C (MFSD7C) uncouples respiration switch in response heme. When heme levels low, MSFD7C promotes by interacting with components electron transport chain (ETC) complexes III, IV, V, destabilizing sarcoendoplasmic reticulum Ca 2+ -ATPase 2b...
Velocardiofacial syndrome (VCFS) is a common, phenotypically heterogeneous developmental disorder caused by an interstitial microdeletion within human chromosome 22q11. The deleted chromosomal region in >90% of VCFS patients includes the GPIb beta gene, encoding for one subunit platelet GPIb-V-IX receptor, which critical adhesion under shear, and important aggregation thrombin-mediated activation. Complete loss due to autosomal recessive inheritance two alpha, Ib or GP9 gene mutations,...
Although there is an increased cardiovascular risk in the immediate weeks following bereavement, mechanism not well understood. The aim of this study was to determine whether inflammatory and thrombotic changes were present acute bereavement. Eighty bereaved spouses or parents prospectively studied within 2 bereavement (acute) at 6 months, compared 80 non-bereaved participants. Haemostatic measures obtained between 8 a.m. 11 processed 1 h. Compared participants, those acutely had a higher...
Abstract Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present genome-wide functional characterization sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum (henceforth referred to as S. bayanus), allowing us map changes over 20 million years separate this organism...