- Sirtuins and Resveratrol in Medicine
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Cancer, Lipids, and Metabolism
- Renal cell carcinoma treatment
- Autophagy in Disease and Therapy
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- DNA Repair Mechanisms
- Biochemical effects in animals
- Calcium signaling and nucleotide metabolism
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Histone Deacetylase Inhibitors Research
- Pancreatic and Hepatic Oncology Research
- Telomeres, Telomerase, and Senescence
- Tea Polyphenols and Effects
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Cancer Mechanisms and Therapy
- CRISPR and Genetic Engineering
- Melanoma and MAPK Pathways
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Acute Lymphoblastic Leukemia research
Sylvester Comprehensive Cancer Center
2022-2025
University of Miami
2022-2025
Miami VA Healthcare System
2023-2025
University of Michigan
2015-2024
Jackson Memorial Hospital
2024
Bruce W. Carter VA Medical Center
2024
Michigan United
2012-2023
Michigan Medicine
2012-2022
U-M Rogel Cancer Center
2020
Ann Arbor Center for Independent Living
2020
We demonstrate a role for the NAD-dependent deacetylase Sirt1 in regulation of autophagy. In particular, transient increased expression is sufficient to stimulate basal rates addition, we show that Sirt1(-/-) mouse embryonic fibroblasts do not fully activate autophagy under starved conditions. Reconstitution with wild-type but deacetylase-inactive mutant restores these cells. further can form molecular complex several essential components machinery, including genes (Atg)5, Atg7, and Atg8....
Homologs of the Saccharomyces cerevisiae Sir2 protein, sirtuins, promote longevity in many organisms. Studies sirtuin SIRT3 have so far been limited to cell culture systems. Here, we investigate localization and function vivo. We show that endogenous mouse is a soluble mitochondrial protein. To address relevance regulation energy metabolism, generated phenotypically characterized knockout mice. SIRT3-deficient animals exhibit striking protein hyperacetylation, suggesting major deacetylase....
Protein post-translational modifications (PTMs) at the lysine residue, such as methylation, acetylation, and ubiquitination, are diverse, abundant, dynamic. They play a key role in regulation of diverse cellular physiology. Here we report discovery new type PTM, malonylation (Kmal). Kmal was initially detected by mass spectrometry protein sequence-database searching. The modification comprehensively validated Western blot, tandem MS, high-performance liquid chromatography synthetic peptides,...
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...
Sirt3 is a member of the sirtuin family protein deacetylases that localized in mitochondria and regulates mitochondrial function. expression skeletal muscle decreased models type 1 2 diabetes regulated by feeding, fasting, caloric restriction. knockout mice exhibit oxygen consumption develop oxidative stress muscle, leading to JNK activation impaired insulin signaling. This effect mimicked knockdown cultured myoblasts, which reduced oxidation, increased reactive species, JNK, serine tyrosine...
B7 delivers a costimulatory signal through CD28, resulting in interleukin-2 secretion and T cell proliferation. Blockade of this pathway results anergy. The vivo role was evaluated with B7-deficient mice. These mice had 70 percent decrease costimulation the response to alloantigen. Despite lacking expression, activated B cells from these bound CTLA-4 GL1 monoclonal antibody, demonstrating that alternative ligand or ligands exist. receptors are functionally important because residual...
Following occupancy of the T cell receptor by antigen, proliferation and lymphokine production are determined a second costimulatory signal delivered ligand expressed on antigen presenting cells. The human B activation B7, which is cells including activated gamma interferon treated monocytes, has been shown to deliver such upon attachment its cells, CD28. We have cloned sequenced murine homologue B7 gene. predicted protein 44% amino acid identity with B7. greatest similarity in Ig-V Ig-C...
Telomere shortening is a well-characterized cellular aging mechanism, and short telomere syndromes cause age-related disease. However, whether long length advantageous poorly understood.
Abstract CTLA-4 is an adhesion receptor expressed on activated T cells. The amino acid sequence of related to CD28, and although the function remains unknown, it shares several features with including a common counter-receptor, B7, that present Ag-presenting In recent study we found CD28 were coexpressed at mRNA level cells but only was resting Here show within cell population, expression restricted subset also express surface CD28. can be induced quiescent via phorbol ester-mediated...