A5006001864- Selenium in Biological Systems
- Fungal and yeast genetics research
- Genetics, Aging, and Longevity in Model Organisms
- Endoplasmic Reticulum Stress and Disease
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Trace Elements in Health
- Redox biology and oxidative stress
- Adipose Tissue and Metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Ubiquitin and proteasome pathways
- Bioinformatics and Genomic Networks
- Medical and Biological Ozone Research
- Peptidase Inhibition and Analysis
- RNA regulation and disease
- Plant Stress Responses and Tolerance
- Spaceflight effects on biology
- Sperm and Testicular Function
- Signaling Pathways in Disease
- Genomics, phytochemicals, and oxidative stress
- Birth, Development, and Health
- Thyroid Disorders and Treatments
- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
Boston University
2016-2024
University School
2020
National Cancer Institute
2009-2014
National Institutes of Health
2009-2014
Center for Cancer Research
2009-2014
Brigham and Women's Hospital
2009-2014
Cancer Genetics (United States)
2014
Harvard University
2009-2014
University of Nebraska–Lincoln
2005-2009
Institute of Molecular Biology and Genetics
2003
Selenium has significant health benefits, including potent cancer prevention activity and roles in immune function the male reproductive system. Selenium-containing proteins, which incorporate this essential micronutrient as selenocysteine, are proposed to mediate positive effects of dietary selenium. Presented here solution NMR structures selenoprotein SelM an ortholog Sep15. These data reveal that Sep15 structural homologs establish a new thioredoxin-like protein family. The location...
Selenium (Se) is an essential trace element in mammals that has been shown to exert its function through selenoproteins. Whereas optimal levels of Se the diet have important health benefits, a recent clinical trial suggested supplemental intake above adequate level potentially may raise risk type 2 diabetes mellitus. However, molecular mechanisms for effect dietary on development this disease are not understood. In present study, we examined contribution selenoproteins increased developing...
To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in field. While highlighting some common features aging, exposed broad disagreement on foundational issues. What is aging? causes it? When does it begin? constitutes rejuvenation? Not only was there no consensus these and other core questions, but none questions received majority opinion-even regarding need for itself. Despite many believing understand their understanding...
The accumulation of misfolded proteins in the endoplasmic reticulum (ER) results activation signaling pathways collectively known as unfolded protein response (UPR). UPR promotes adaptation cells to ER stress by transient inhibition translation and transcriptional up-regulation genes encoding chaperones, oxidoreductases, ER-associated degradation components. However, it may also trigger apoptosis persistent stress. Recently, a novel selenocysteine-containing oxidoreductase, Sep15, has been...
Cells respond to accumulation of misfolded proteins in the endoplasmic reticulum (ER) by activating unfolded protein response (UPR) signaling pathway. The UPR restores ER homeostasis degrading proteins, inhibiting translation, and increasing expression chaperones that enhance folding capacity. Although stress aggregation have been implicated aging, role regulating lifespan remains unknown. Here we show deletion several target genes significantly increases replicative yeast. This extended...
Selenium is an essential trace element with potent cancer prevention activity in mammals. The 15-kDa selenoprotein (Sep15) has been implicated the chemopreventive effect of dietary selenium. Although precise function Sep15 remains elusive, co-purifies UDP-glucose:glycoprotein glucosyltransferase (GT), regulator quality control mechanisms within endoplasmic reticulum. Recent studies identified two GT and homologues We characterize interactions between these protein families this report. form...
Mammalian selenoproteins have diverse functions, cellular locations, and evolutionary histories, but all use the amino acid selenocysteine (Sec), often present in enzyme's active site. Only about half of mammalian been functionally characterized, with most being oxidoreductases. The role selenoprotein T (SelT), manifesting a CxxU motif thioredoxin-like fold localized to Golgi endoplasmic reticulum, is not known. To examine its biological function, we knocked down SelT expression mouse...
The yeast genome becomes unstable during stress, which often results in adaptive aneuploidy, allowing rapid activation of protective mechanisms that restore cellular homeostasis. In this study, we performed a genetic screen Saccharomyces cerevisiae to identify adaptations confer resistance tunicamycin-induced endoplasmic reticulum (ER) stress. Whole-genome sequencing tunicamycin-resistant mutants revealed ER stress correlated significantly with gains chromosomes II and XIII. We found...
N-terminal acetylation of the first two amino acids on proteins is a prevalent cotranslational modification. Despite its abundance, biological processes associated with this modification are not well understood. Here, we mapped pattern protein in Caenorhabditis elegans, uncovering conserved set rules for and identifying substrates acetyltransferase B (NatB) complex. We observed an enrichment global also specifically NatB nucleus, supporting importance regulating functions within cellular...
Transcriptional regulation plays an important role in the control of gene expression during aging. However, translation efficiency likely equally determining protein abundance, but it has been relatively understudied this context. Here, we used RNA sequencing (RNA-seq) and ribosome profiling to investigate translational lifespan extension by CAN1 deletion yeast. Through comparison transcriptional changes cells lacking with other long-lived mutants, were able identify critical regulatory...
Iron dyshomeostasis contributes to aging, but little information is available about the molecular mechanisms. Here, we provide evidence that in Saccharomyces cerevisiae, aging associated with altered expression of genes involved iron homeostasis. We further demonstrate defects conserved mRNA-binding protein Cth2, which controls stability and translation mRNAs encoding iron-containing proteins, increase lifespan by alleviating its repressive effects on mitochondrial function. Mutation...
Abstract Being a simple eukaryotic organism, Saccharomyces cerevisiae provides numerous advantages for expression and functional characterization of proteins from higher eukaryotes, including humans. However, studies complex exogenous pathways using yeast as host have been hampered by the lack tools to engineer strains expressing large number genetic components. In addition inserting multiple genes, it is often desirable knock out or replace endogenous genes that might interfere with...
Abstract Protein synthesis is a highly energy-consuming process that downregulated in response to many environmental stresses or adverse conditions. Studies the yeast Saccharomyces cerevisiae have shown bulk translation inhibited during adaptation iron deficiency, which consistent with its requirement for ribosome biogenesis and recycling. Although deficiency anemia most common human nutritional disorder, how modulates mammals poorly understood. erythropoiesis bioavailability coordinated...