A5081962222- Sirtuins and Resveratrol in Medicine
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- RNA and protein synthesis mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Genomics, phytochemicals, and oxidative stress
- Epigenetics and DNA Methylation
- Tea Polyphenols and Effects
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- Cancer-related gene regulation
- RNA regulation and disease
- Calcium signaling and nucleotide metabolism
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Peptidase Inhibition and Analysis
- Cancer-related Molecular Pathways
- Toxin Mechanisms and Immunotoxins
VA Palo Alto Health Care System
2013-2024
Geriatric Research Education and Clinical Center
2012-2024
Stanford University
2012-2024
Howard Hughes Medical Institute
2002-2008
Harvard University
1997-2006
National Institutes of Health
2003
National Cancer Institute
2003
Tufts University
2003
Beth Israel Deaconess Medical Center
2002
Dana-Farber Cancer Institute
2002
The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which increases longevity are largely unknown. We show that mammalian cells, homolog SIRT1 appears to control cellular response stress regulating FOXO family of Forkhead transcription factors, a proteins function as sensors insulin signaling pathway and regulators longevity. factor FOXO3 formed complex cells oxidative stress, deacetylated vitro within cells. had dual effect on...
SIRT1 is a mammalian homolog of the Saccharomyces cerevisiae chromatin silencing factor Sir2. Dominant-negative and overexpression studies have implicated role for in deacetylating p53 tumor suppressor protein to dampen apoptotic cellular senescence pathways. To elucidate function normal cells, we used gene-targeted mutation generate mice that express either mutant lacks part catalytic domain or has no detectable at all. Both types cells had essentially same phenotypes. were small, exhibited...
Posttranslational modifications play important roles in regulating protein structure and function. Histone deacetylase 6 (HDAC6) is a mostly cytoplasmic class II HDAC, which has unique with two catalytic domains domain binding ubiquitin high affinity. This enzyme was recently identified as multisubstrate that can act on acetylated histone tails, α-tubulin Hsp90. To investigate the vivo functions of HDAC6 relevance tubulin acetylation/deacetylation, we targeted gene by homologous...
In mammalian cells, DNA double-strand breaks (DSBs) cause rapid phosphorylation of the H2AX core histone variant (to form γ-H2AX) in megabase chromatin domains flanking sites damage. To investigate role we generated H2AX-deficient (H2AX Δ / ) mouse embryonic stem (ES) cells. ES cells are viable. However, they highly sensitive to ionizing radiation (IR) and exhibit elevated levels spontaneous IR-induced genomic instability. Notably, is not required for NHEJ per se because support normal...
Aging | doi:10.18632/aging.100011. Ronald A. McCord, Eriko Michishita, Tao Hong, Elisabeth Berber, Lisa D. Boxer, Rika Kusumoto, Shenheng Guan, Xiaobing Shi, Or Gozani, Alma L. Burlingame, Vilhelm Bohr, Katrin F. Chua
Nonalcoholic fatty liver disease is the most common chronic disorder in developed countries. Its pathogenesis poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD+-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress prevent development of disease. SIRT7 induced upon stabilized promoters ribosomal proteins through its interaction with transcription factor Myc silence gene expression relieve stress. SIRT7-deficient mice develop...