A5024662272- Metabolomics and Mass Spectrometry Studies
- Eicosanoids and Hypertension Pharmacology
- Cancer, Hypoxia, and Metabolism
- Fatty Acid Research and Health
- Alcohol Consumption and Health Effects
- SARS-CoV-2 and COVID-19 Research
- Epigenetics and DNA Methylation
- SARS-CoV-2 detection and testing
- Liver Disease Diagnosis and Treatment
- Diet and metabolism studies
- CRISPR and Genetic Engineering
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Gene expression and cancer classification
- Metabolism, Diabetes, and Cancer
- Diet, Metabolism, and Disease
- Bioinformatics and Genomic Networks
- Nutritional Studies and Diet
- Virus-based gene therapy research
- Advanced Proteomics Techniques and Applications
- Child Nutrition and Water Access
- Lipid metabolism and biosynthesis
- Infant Nutrition and Health
- Spondyloarthritis Studies and Treatments
- Virology and Viral Diseases
University of California, San Diego
2018-2025
Chapman University
2025
Broad Institute
2020-2023
Harvard University
2020-2023
Cedars-Sinai Medical Center
2019
Cedars-Sinai Smidt Heart Institute
2019
Replacing or editing disease-causing mutations holds great promise for treating many human diseases. Yet, delivering therapeutic genetic modifiers to specific cells in vivo has been challenging, particularly large, anatomically distributed tissues such as skeletal muscle. Here, we establish an strategy evolve and stringently select capsid variants of adeno-associated viruses (AAVs) that enable potent delivery desired tissues. Using this method, identify a class RGD motif-containing capsids...
Phylogenetics of superspreading One important characteristic coronavirus epidemiology is the occurrence events. These are marked by a disproportionate number cases originating from often-times asymptomatic individuals. Using rich sequence dataset early stages Boston outbreak, Lemieux et al. identified events in specific settings and analyzed them phylogenetically (see Perspective Alizon). ancestral trait inference, authors several importation events, further investigated context contribution...
Adeno-associated virus (AAV) vectors are a promising vehicle for noninvasive gene delivery to the central nervous system via intravenous infusion. However, naturally occurring serotypes have limited ability transduce brain, and translating engineered capsids from mice nonhuman primates has proved challenging.In this study, we use an mRNA-based directed-evolution strategy in multiple strains of as well de novo selection cynomolgus macaques identify families with increased potency brain...
Longevity in mammals is influenced by sex, and lifespan extension response to anti-aging interventions often sex-specific, although the mechanisms underlying these sexual dimorphisms are largely unknown. Treatment of mice with 17-α estradiol (17aE2) results sex-specific extension, an increase median survival males 19% no effect females. Given links between metabolism, we performed untargeted metabolomics analysis liver, skeletal muscle plasma from male female treated 17aE2 for eight months....
Abstract SARS-CoV-2 has caused a severe, ongoing outbreak of COVID-19 in Massachusetts with 111,070 confirmed cases and 8,433 deaths as August 1, 2020. To investigate the introduction, spread, epidemiology Boston area, we sequenced analyzed 772 complete genomes from region, including nearly all within first week epidemic hundreds major outbreaks at conference, nursing facility, among homeless shelter guests staff. The data reveal over 80 introductions into predominantly elsewhere United...
There is a growing trend in the use of severe caloric restrictive diets among normal weight young females that can jeopardize bone health. Using an animal model, purpose this study was to determine whether resistance training (RT) could maintain health during 6-week (CR) diet female rats. Twenty-four rats (~ 8 weeks old) were randomly divided into following groups: sedentary fed (N = 8), 40% CR (D and RT group (DT 8). The DT climbed vertical ladder four consecutive times (per exercise...
Cardiolipin (CL) is a signature phospholipid of the mitochondria required for formation mitochondrial respiratory chain (MRC) supercomplexes. The destabilization MRC supercomplexes proximal cause pathology associated with depletion CL in patients Barth syndrome. Thus, promoting supercomplex could ameliorate dysfunction depletion. However, to date, physiologically relevant small-molecule regulators have not been identified. Here, we report that ethanolamine (Etn) supplementation rescues...
Background Epidemiological and animal studies have associated systemic inflammation with blood pressure (BP). However, the mechanistic factors linking BP remain unknown. Fatty acid-derived eicosanoids serve as mediators of been suggested to regulate renal vascular tone, peripheral resistance, renin-angiotensin system, endothelial function. We hypothesize that specific proinflammatory anti-inflammatory are linked BP. Methods Results studied a population sample 8099 FINRISK 2002 participants...
Emerging technologies now allow for mass spectrometry-based profiling of thousands small molecule metabolites ('metabolomics') in an increasing number biosamples. While offering great promise insight into the pathogenesis human disease, standard approaches have not yet been established statistically analyzing increasingly complex, high-dimensional metabolomics data relation to clinical phenotypes, including disease outcomes. To determine optimal analysis, we formally compare traditional and...
Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to risk biomarkers are unclear. We hypothesized that n-3 is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid inflammatory biomarkers. examined these VITAL200, a nested substudy of 200 subjects balanced demographics randomly selected from Vitamin D Trial (VITAL). VITAL randomized double-blind trial 840 mg/d...
To assist with management and interpretation of human metabolomics data, which are rapidly increasing in quantity complexity, we need better visualization tools. Using a dataset several hundred metabolite measures profiled cohort ~1500 individuals sampled from population-based community study, performed association analyses eight demographic clinical traits outcomes. We compared frequently used existing graphical approaches novel ‘rain plot’ approach to display the results these analyses....
Abstract Introduction Choline is an essential human nutrient that particular important for proliferating cells, and altered choline metabolism has been associated with cancer transformation. Yet, the various metabolic fates of in cells have not investigated systematically. Objectives This study aims to map products normal cancerous cells. Methods We performed 13 C-choline tracing followed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) analysis vitro-transformed...
The metabolism of branched-chain amino acids (BCAA) has recently been implicated in the growth several cancer cell types. Gabapentin, a synthetic acid, is commonly used high concentrations this context to inhibit cytosolic acid transferase (BCAT1) enzyme. Here, we report that 10 mM gabapentin reduces HCT116 cells, which have an active but express very low levels BCAT1, and presumably rely on mitochondrial BCAT2 Gabapentin did not affect transamination BCAA keto (BCKA) nor reverse formation...
Proliferating cells must synthesize a wide variety of macromolecules while progressing through the cell cycle, but coordination between cycle progression and cellular metabolism is still poorly understood. To identify metabolic processes that oscillate over we performed comprehensive, non-targeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) based metabolomics HeLa isolated in G1 SG2M phases, capturing thousands diverse metabolite ions. When accounting for increased...