A5050979856- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- Genomics, phytochemicals, and oxidative stress
- Cell Image Analysis Techniques
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Protein Degradation and Inhibitors
- Genomics and Phylogenetic Studies
- Circadian rhythm and melatonin
- Mitochondrial Function and Pathology
- Invertebrate Immune Response Mechanisms
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Acute Myeloid Leukemia Research
- Cellular Mechanics and Interactions
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Insect symbiosis and bacterial influences
- Aquaculture disease management and microbiota
Harvard University
2014-2024
Abeona Therapeutics (United States)
2024
Harvard University Press
2024
Joslin Diabetes Center
2014-2023
Harvard Stem Cell Institute
2015-2023
Constellation Pharmaceuticals (United States)
2019-2022
Morpho (United States)
2022
University of Michigan–Ann Arbor
2009-2012
In Caenorhabditis elegans, ablation of germline stem cells (GSCs) extends lifespan, but also increases fat accumulation and alters lipid metabolism, raising the intriguing question how these effects might be related. Here, we show that a lack GSCs results in broad transcriptional reprogramming which conserved detoxification regulator SKN-1/Nrf stress resistance, proteasome activity, longevity. SKN-1 activates diverse metabolism genes reduces storage, thereby alleviating increased caused by...
blood cells, called hemocytes, are classified into plasmatocytes, crystal and lamellocytes based on the expression of a few marker genes cell morphologies, which inadequate to classify complete hemocyte repertoire. Here, we used single-cell RNA sequencing (scRNA-seq) map hemocytes across different inflammatory conditions in larvae. We resolved plasmatocytes states involved cycle, antimicrobial response, metabolism together with identification intermediate states. Further, discovered rare...
Aging is closely associated with increased susceptibility to breast cancer, yet there have been limited systematic studies of aging-induced alterations in the mammary gland. Here, we leverage high-throughput single-cell RNA sequencing generate a detailed transcriptomic atlas young and aged murine tissues. By analyzing epithelial, stromal, immune cells, identify age-dependent cell proportions gene expression, providing evidence that suggests alveolar maturation physiological decline. The...
Although excessive lipid accumulation is a hallmark of obesity-related pathologies, some lipids are beneficial. Oleic acid (OA), the most abundant monounsaturated fatty (FA), promotes health and longevity. Here, we show that OA benefits Caenorhabditis elegans by activating endoplasmic reticulum (ER)-resident transcription factor SKN-1A (Nrf1/NFE2L1) in homeostasis response. SKN-1A/Nrf1 cleared from ER ER-associated degradation (ERAD) machinery stabilized when proteasome activity low...
Xenobiotic metabolism has been proposed to play a role in modulating the rate of aging. metabolizing enzymes (XME) are expressed at higher levels calorically restricted mice (CR) and GH/IGF-I-deficient, long-lived mutant mice. In this study, we show that many phase I XME genes similarly upregulated additional mouse models, including "crowded litter" (CL) mice, whose lifespan increased by food restriction limited first 3 wk life, treated with rapamycin. Induction CL lasts least through 22 mo...
Individually, dysfunction of both the endoplasmic reticulum (ER) and mitochondria has been linked to aging, but how communication between these organelles might be targeted promote longevity is unclear. Here, we provide evidence that, in Caenorhabditis elegans, inhibition conserved unfolded protein response (UPRER) mediator, activating transcription factor (atf)-6, increases lifespan by modulating calcium homeostasis signaling mitochondria. Atf-6 loss confers via downregulation ER buffer,...
Background: Atrial fibrillation (AF) is the most common clinical arrhythmia and associated with heart failure, stroke, increased mortality. The myocardial substrate for AF poorly understood because of limited access to primary human tissue mechanistic questions around existing in vitro or vivo models. Methods: Using an MYH6:mCherry knock-in reporter line, we developed a protocol generate highly purify pluripotent stem cell–derived cardiomyocytes displaying physiological molecular...
<ns4:p>RNA-seq analysis involves multiple steps, from processing raw sequencing data to identifying, organizing, annotating, and reporting differentially expressed genes. bcbio is an open source, community-maintained framework providing automated scalable RNA-seq methods for identifying gene abundance counts. We have developed bcbioRNASeq, a Bioconductor package that provides ready-to-render templates, objects wrapper functions post-process RNA output data. bcbioRNASeq helps automate the...
Significance Mitochondria play a vital role in cellular life. Understanding how mitochondria are regulated may uncover new ways to restore mitochondrial function disease states. Here we use an unbiased, pooled ORFeome library screening strategy identify 94 candidate regulator genes. We show that one of the genes, glioma tumor-suppressor region gene 2 (GLTSCR2), controls cultured cells and Caenorhabditis elegans . The transcription factor Myc is key downstream mediator GLTSCR2 signaling....
Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for positive breast cancer (ER+ BC), but sustained response limited by acquired resistance. Targeting transcriptional coactivators required activity represents an alternative that not subject to same limitations as itself. In this report we demonstrate acetyltransferase coactivator paralogs CREBBP/EP300 promising therapeutic target in ER+ BC. Using potent and selective inhibitor CPI-1612, show inhibition...
Targeting synthetic lethal interactions between genes has emerged as a promising strategy for cancer therapy. This study explores the intricate interplay terminal uridyltransferase 4 (TUT4) and 7 (TUT7), 3'-5' exoribonuclease DIS3L2, SKI complex-interacting factor Focadhesin (FOCAD) in context of vulnerability. Using CRISPR public functional genomics data, we show impairment cell proliferation upon knockout TUT7 or but not TUT4, on cells with FOCAD loss. Moreover, report characterization...
Summary Drosophila blood cells, called hemocytes, are classified into plasmatocytes, crystal and lamellocytes based on the expression of a few marker genes cell morphologies, which inadequate to classify complete hemocyte repertoire. Here, we used single-cell RNA sequencing (scRNA-seq) map hemocytes across different inflammatory conditions in larvae. We resolved plasmatocytes states involved cycle, antimicrobial response, metabolism together with identification intermediate states. Further,...
<ns5:p>RNA-seq analysis involves multiple steps from processing raw sequencing data to identifying, organizing, annotating, and reporting differentially expressed genes. bcbio is an open source, community-maintained framework providing automated scalable RNA-seq methods for identifying gene abundance counts. We have developed bcbioRNASeq, a Bioconductor package that provides ready-to-render templates wrapper functions post-process output data. bcbioRNASeq automates the generation of...
Breakdown of lipid homeostasis is thought to contribute pathological aging, the largest risk factor for neurodegenerative disorders such as Alzheimer's Disease (AD). Cognitive reserve theory posits a role compensatory mechanisms in aging brain preserving neuronal circuit functions, staving off cognitive decline, and mitigating AD. However, identities have remained elusive. A screen hippocampal dentate granule cell (DGC) synapse loss-induced factors identified secreted phospholipase
<title>Abstract</title> Breakdown of lipid homeostasis is thought to contribute pathological aging, the largest risk factor for neurodegenerative disorders such as Alzheimer’s Disease (AD). Cognitive reserve theory posits a role compensatory mechanisms in aging brain preserving neuronal circuit functions, staving off cognitive decline, and mitigating AD. However, identities have remained elusive. A screen hippocampal dentate granule cell (DGC) synapse loss-induced factors identified secreted...
<p>Related to Figure 2</p>
<p>Supplementary Materials and Methods</p>
<div>Abstract<p>Targeting synthetic lethal interactions among genes has emerged as a promising strategy for cancer therapy. This study explores the intricate interplay terminal uridylyltransferase 4 (TUT4) and 7 (TUT7), 3′-5′ exoribonuclease DIS3L2, superkiller (SKI) complex–interacting factor focadhesin (FOCAD) in context of vulnerability. Using CRISPR public functional genomics data, we show impairment cell proliferation upon knockout TUT7 or but not TUT4, on cells with...