Dr. Charles Brenner was recently interviewed by Dr. Kazuo Tzubota, President of the Japanese Society of Anti-Aging Medicine, on the topic of NAD, nicotinamide riboside supplementation and aging. The interview was published in the Society's magazine Anti-Aging Medicine, read the full interview here.
Cellular function and differentiation depend on an ability to read environmental cues and to execute a gene expression program that is appropriate to time, place and context. Nutrient availability is among the most important signals to which cells respond. Importantly, nutrients are not only transmitted from outside an organism, i.e., by feeding, but are also transmitted from cell to cell and from tissue to tissue. Metabolic control of gene expression is critical to the maintenance of cellular longevity. Dysregulation of the nutritional control of gene expression underlies a series of conditions including nondetection of satiety, which can lead to obesity and diabetes, and diseases such as cancer.
Our laboratory is engaged in several projects that dissect specific problems in the metabolic control of gene expression. In particular, we are interested in how changing environmental conditions lead to reversible transfer of two carbon, i.e. acetyl, and one carbon, i.e. methyl, groups to proteins and DNA, respectively. These processes are fundamentally important because two carbon transfers link carbohydrate and fat metabolism to nicotinamide adenine dinucleotide (NAD) biosynthesis and because one carbon transfers link the folate cycle and methionine biosynthesis to S-adenosyl methionine metabolism. Trainees in our group are engaged in interdisciplinary projects, performing protein purification, enzymology, structural biology, yeast and somatic cell genetics, genomics, and chemical biology.
For more information on current projects, see the current research page.
J. Ratajczak, M. Joffraud, S.A.J. Trammell, R. Ras, N. Canela, M. Boutant, S.S. Kulkarni, M. Rodrigues, P. Redpath, M.E. Migaud, J. Auwerx, O. Yanes, C. Brenner & C. Canto, "NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells." Nature Communications. v. 7, pp. 13103. DOI: 10.1038/ncomms13103. Download pdf reprint.
S.A.J. Trammell, M.S. Schmidt, B.J.Weidemann, P. Redpath, F. Jaksch, R.W. Dellinger, Z. Li, E.D. Abel, M.E. Migaud & C. Brenner, “Nicotinamide riboside is uniquely and orally bioavailable in mice and humans,” Nature Communications, v. 7, 12948 (2016). DOI: 10.1038/ncomms12948. reprint.
S.A.J. Trammell, B.J.Weidemann, A.Chadda, M.S. Yorek, A. Holmes, L.J.Coppey, A. Obrosov, R.H. Kardon, M.A. Yorek & C. Brenner, “Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice,” Scientific Reports, v. 6, 26933 (2016). DOI: 10.1038/srep26933. Download pdf reprint.
B.-K. Wu & C. Brenner, "Suppression of TET1-Dependent DNA Demethylation is Essential for KRAS-Mediated Transformation," Cell Reports, v. 9, pp. 1827-1840 (2014). DOI:10.1016/j.celrep.2014.10.063. Download pdf reprint.
R.L. Fagan, D.E. Cryderman, L. Kopelovich, L.L. Wallrath & C. Brenner, "Laccaic Acid A is a Direct, DNA-Competitive Inhibitor of DNA Methyltransferase 1," J Biol Chem, v.288, pp. 23858-23867 (2013). DOI: 10.1074/jbc.M113.480517. Download pdfreprint.
S. Ghanta, R.E. Grossmann & C. Brenner, "Mitochondrial protein acetylation as a cell-intrinsic, evolutionary driver of fat storage: chemical and metabolic logic of acetyl-lysine modifications" Critical Rev Biochem & Mol Biol, v. 48, pp. 561-574 (2013). Download pdf reprint.
S.A.J. Trammell & C. Brenner, "Targeted, LCMC-Based Metabolomics for Quantitative Measurement of NAD+ Metabolites," Computational and Structural Biotechnology Journal, v. 4, e201301012 (2013). DOI: 10.5936/csbj.201301012. Download pdf reprint.
F. Syeda, R.L. Fagan, M. Wean, G.V. Awakumov, J.R. Walker, S. Xue, S. Dhe-Paganon, & C. Brenner, "The RFTS Domain is a DNA-competitive Inhibitor of Dnmt1", JBC, v. 286, pp. 15344-15351 (2011). Download pdf reprint.
P. Belenky, F.G. Racette, K.L. Bogan, J.M. McClure, J.S. Smith & C. Brenner, "Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+," Cell, v. 129, pp. 473-484 (2007). Download pdf reprint.
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- Molecular & Cellular Biology Ph.D. Program
- Genetics Ph.D. Program
- Holden Comprehensive Cancer Center
- Center for Biocatalysis and Bioprocessing