A5086649578- Diabetes, Cardiovascular Risks, and Lipoproteins
- interferon and immune responses
- Cellular transport and secretion
- Children's Physical and Motor Development
- RNA regulation and disease
- Cholesterol and Lipid Metabolism
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Pineapple and bromelain studies
- Phytoplasmas and Hemiptera pathogens
- Autophagy in Disease and Therapy
- Photosynthetic Processes and Mechanisms
- Liver Disease Diagnosis and Treatment
- Advanced Chemical Physics Studies
- Iron oxide chemistry and applications
- Health, Environment, Cognitive Aging
- Mitochondrial Function and Pathology
- Lipid metabolism and disorders
- Genetic Associations and Epidemiology
- Nuclear Receptors and Signaling
- Metabolomics and Mass Spectrometry Studies
Yale University
2018-2025
Howard Hughes Medical Institute
2018-2025
Research Network (United States)
2021-2025
University of Pennsylvania
2014-2021
Sorbonne Université
2016-2017
Inserm
2014-2017
Assistance Publique – Hôpitaux de Paris
2014-2017
Pitié-Salpêtrière Hospital
2017
Franklin & Marshall College
2012-2014
Allan Hancock College
2014
Mutations in the human VPS13 genes are responsible for neurodevelopmental and neurodegenerative disorders including chorea acanthocytosis (VPS13A) Parkinson’s disease (VPS13C). The mechanisms of these diseases unknown. Genetic studies yeast hinted that Vps13 may have a role lipid exchange between organelles. In this study, we show N-terminal portion is tubular, with hydrophobic cavity can solubilize transport glycerolipids membranes. We also VPS13A VPS13C bind to ER, tethering it...
A scavenger that protects the heart Coronary disease is a tale of two forms plasma cholesterol. In contrast to well-established effects “bad” cholesterol (LDL-C), role “good” (HDL-C) mysterious. Elevated HDL-C correlates with lower risk disease, yet drugs raise levels do not reduce risk. Zanoni et al. found some people exceptionally high carry rare sequence variant in gene encoding major receptor, receptor BI. This destroys receptor's ability take up HDL-C. Interestingly, this have higher...
Mutations in VPS13C cause early-onset, autosomal recessive Parkinson’s disease (PD). We have established that encodes a lipid transfer protein localized to contact sites between the ER and late endosomes/lysosomes. In current study, we demonstrate depleting HeLa cells causes an accumulation of lysosomes with altered profile, including di-22:6-BMP, biomarker PD-associated leucine-rich repeat kinase 2 (LRRK2) G2019S mutation. addition, DNA-sensing cGAS-STING pathway, which was recently...
VPS13 is a eukaryotic lipid transport protein localized at membrane contact sites. Previous studies suggested that it may transfer lipids between adjacent bilayers by bridge-like mechanism. Direct evidence for this hypothesis from full-length structure and electron microscopy (EM) in situ still missing, however. Here, we have capitalized on AlphaFold predictions to complement the structural information already available about generate model of human VPS13C, Parkinson's disease-linked paralog...
Based on genetic studies, lysosome dysfunction is thought to play a pathogenetic role in Parkinson's disease (PD). Here we show that VPS13C, bridge-like lipid transport protein and PD gene, sensor of stress/damage. Upon membrane perturbation, VPS13C rapidly relocates from the cytosol surface lysosomes where it tethers their membranes ER. This recruitment depends Rab7 requires signal at damaged releases an inhibited state which hinders access its VAB domain lysosome-bound Rab7. While another...
Abstract VPS13 is a eukaryotic lipid transport protein localized at membrane contact sites. Previous studies suggested that it may transfer lipids between adjacent bilayers by bridge-like mechanism. Direct evidence for this hypothesis from full-length structure and EM in situ , however, still missing. Here we have capitalized on AlphaFold predictions to complement the structural information already available about generate model of human VPS13C, Parkinson’s disease-linked paralog contacts ER...
Medical education is lagging behind advances in planetary health knowledge due to the considerable barriers introducing new topics into medical curricula. This potentially leaves doctors of future ill-equipped deal with challenges associated environmental degradation. The recently conceived ‘infusion’ approach by Icahn School Medicine at Mount Sinai, New York, USA, represents a promising method for integrating education. Adopting this approach, International Education Collaboration on...
Genome-wide association studies have uncovered common variants at many loci influencing human complex traits, such as high-density lipoprotein cholesterol (HDL-C). However, the contribution of identified genes is difficult to ascertain from current efforts interrogating with small effects. Thus, there a pressing need for scalable, cost-effective strategies uncovering causal variants, which may be rare and noncoding.Here, we used molecular inversion probe target capture approach resequence...
cis,anti,cis-Tricyclo[7.4.0.0(2,8)]tridec-10-ene (13TCT) undergoes [1,3] sigmatropic rearrangements at 315 °C in the gas phase to si product 1 and sr 2 with si/sr = 2.1. The dominant thermal isomerization process, however, is epimerization C8 afford 3. That stereomutation occurs 50% faster than shifts combined.
The title compound 1-exo (with minor amounts of its C8 epimer 1-endo) was prepared by Wolff-Kishner reduction the cycloadduct 1,3-cyclohexadiene and cyclopropylketene. [1,3]-migration product 2-endo synthesized efficient selective cyclopropanation endo-5-vinylbicyclo[2.2.2]oct-2-ene at exocyclic π-bond. Gas phase thermal reactions afforded epimerization to 1-endo, [1,3]- migrations 2-exo 2-endo, direct fragmentation cyclohexadiene vinylcyclopropane, CPC rearrangement in following relative...
ABSTRACT Mutations in VPS13C cause early onset, autosomal recessive Parkinson’s Disease (PD). We have established that encodes a lipid transfer protein localized to contact sites between the endoplasmic reticulum (ER) and late endosomes/lysosomes. In current study, we demonstrate depleting HeLa cells causes an accumulation of lysosomes with altered profile, including di-22:6-BMP, biomarker PD-associated leucine-rich repeat kinase 2 (LRRK2) G2019S mutation. addition, DNA-sensing cGAS/STING...
High-density lipoprotein cholesterol (HDL-C) is thought to be atheroprotective yet some patients with elevated HDL-C levels develop cardiovascular disease, possibly due the presence of dysfunctional HDL. We aimed assess metabolic fate circulating HDL particles in high and without coronary artery disease (CAD) using vivo dual labeling its protein moieties. measured apolipoprotein (apo) A-I, apoA-II, free (FC), cholesteryl ester (CE) kinetics stable isotope-labeled tracers (D3-leucine...
A 52-year-old woman presented to the emergency department with severe, acute right-sided abdominal pain that woke her from sleep 5 hours prior, radiated right flank, and had not improved after a bowel movement. She associated nausea non-bilious emesis, but she no diarrhea or fever. significant medical history previous surgeries. screening colonoscopy 1 month prior. Her examination was soft, non-distended, severely tender in midabdominal region. Laboratory results were within normal limits....
This method describes the synthesis and usage of dextran-conjugated superparamagnetic iron nanoparticles (SPIONs)
This method describes the usage of dextran-conjugated superparamagnetic iron nanoparticles (SPIONs) to purify a lysosome fraction from cultured cells.
The membrane protein Scavenger Receptor Class B, Type 1 (SR-BI), coded by the gene SCARB1, facilitates selective uptake of cholesteryl esters from HDL in liver. Its impact on human lipoprotein metabolism however is not fully understood. Our laboratory has recently identified two homozygotes and 16 heterozygotes for a coding mutation SCARB1 (c.1127C>T, p.Pro376Leu). We assessed hypothesis that this significantly increases HDL-C alters composition biological function. Plasma subjects...