A5003759640- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Genetics, Aging, and Longevity in Model Organisms
- Cellular Mechanics and Interactions
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Circadian rhythm and melatonin
- FOXO transcription factor regulation
- Genetics and Neurodevelopmental Disorders
- Protist diversity and phylogeny
- Iron Metabolism and Disorders
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Aging and Gerontology Research
- Genomics and Chromatin Dynamics
- Dietary Effects on Health
- Parvovirus B19 Infection Studies
- HIV Research and Treatment
- Reproductive tract infections research
- Microbial Community Ecology and Physiology
- interferon and immune responses
- Folate and B Vitamins Research
- Intergenerational Family Dynamics and Caregiving
- Marine and coastal ecosystems
- Trace Elements in Health
Brigham and Women's Hospital
2024
Harvard University
2014-2024
Boston Children's Hospital
2014-2024
Washington University in St. Louis
2023-2024
Boston Children's Museum
2024
Harvard Affiliated Emergency Medicine Residency
2020-2021
Stanford University
2005-2011
Howard Hughes Medical Institute
2005
Dana-Farber Cancer Institute
2005
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2001
The maintenance of homeostasis throughout an organism's life span requires constant adaptation to changes in energy levels. AMP-activated protein kinase (AMPK) plays a critical role the cellular responses low levels by switching off energy-consuming pathways and on energy-producing pathways. However, transcriptional mechanisms which AMPK acts adjust are not entirely characterized. Here, we find that directly regulates mammalian FOXO3, member FOXO family Forkhead transcription factors known...
Dietary restriction (DR) has the remarkable ability to extend lifespan and healthspan. A variety of DR regimens have been described in species ranging from yeast mammals. However, whether different via universal, distinct, or overlapping pathways is still an open question. Here we examine genetic that mediate longevity by Caenorhabditis elegans. We previously shown low-energy sensing AMP-activated protein kinase AMPK/aak-2 Forkhead transcription factor FoxO/daf-16 are necessary for induced a...
Aging is accompanied by alterations in epigenetic marks that control chromatin states, including histone acetylation and methylation. Enzymes reversibly affect associated with active have recently been found to regulate aging Caenorhabditis elegans. However, relatively little known about the importance for of repressed chromatin. Here, we use a targeted RNAi screen C. elegans identify four demethylases significantly worm lifespan, UTX-1, RBR-2, LSD-1, T26A5.5. Interestingly, UTX-1 belongs...
Directed DNA methylation on N6-adenine (6mA), N4-cytosine (4mC), and C5-cytosine (5mC) can potentially increase coding capacity regulate a variety of biological functions. These modifications are relatively abundant in bacteria, occurring about percent all bases most bacteria. Until recently, 5mC its oxidized derivatives were thought to be the only directed events metazoa. New more sensitive detection techniques (ultra-high performance liquid chromatography coupled with mass spectrometry...
Proteins with iron–sulfur (Fe–S) clusters participate in multiple metabolic pathways throughout the cell. The mitochondrial ABC half-transporter Abcb7, which is mutated X-linked sideroblastic anemia ataxia humans, a functional ortholog of yeast Atm1p and predicted to export mitochondrially derived metabolite required for cytosolic Fe–S cluster assembly. Using an inducible Cre/loxP system delete exons 9 10 Abcb7 gene, we examined phenotype mice deficient Abcb7. We found that was essential...
How epigenetic information is transmitted from generation to remains largely unknown. Deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase spr-5 leads inherited accumulation euchromatic H3K4me2 mark and progressive decline in fertility. Here, we identified multiple chromatin-modifying factors, including H3K4me1/me2 H3K9me3 methyltransferases, an demethylase, H3K9me reader, which either suppress or accelerate transgenerational phenotypes mutant worms. Our findings...
Aging is regulated by modifications in single genes and simple changes the environment. The signaling pathway connecting insulin to FoxO transcription factors integrates environmental stimuli regulate lifespan. are directly phosphorylated response insulin/growth factor protein kinase Akt, thereby causing their sequestration cytoplasm. In absence of factors, translocate nucleus where they trigger a range cellular responses, including resistance oxidative stress—a phenotype highly coupled with...
The cytotoxic T lymphocyte protease granzyme A (GzmA) initiates a novel caspase-independent cell death pathway characterized by single-stranded DNA nicking. previously identified GzmA substrate SET is in multimeric 270–420-kDa endoplasmic reticulum-associated complex that also contains the tumor suppressor protein pp32. cleaved nucleosome assembly after Lys176 and disrupted its activity. purified required only to reconstitute nicking isolated nuclei. occurred independently of caspase...