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.
Conze, D., Brenner, C. & Kruger, C.L, "Safety and Metabolism of Long-Term Administration of Niagen (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults," Scientific Reports, v. 9, 9772 in press, 2019. Download PDF reprint
P. H. Ear, A. Chadda, S. B. Gumusoglu, M. S. Schmidt, S. Vogeler, J. Malicoat, J. Kadel, M. M. Moore, M. E. Migaud, H. E. Stevens & C. Brenner, "Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring," Cell Reports. v. 26 (4), pp. 969-983 (2019). DOI: 10.1016/j.celrep.2019.01.007. Download PDF reprint
H.W. Liu, C.B. Smith, M.S. Schmidt, X.A. Cambronne, M.S. Cohen, M.E. Migaud, C. Brenner & R.H. Goodman, "Pharmacological bypass of NAD+ salvage pathway protects neurons from chemotherapy-induced degeneration," Proc Natl Acad Sci U S A. v.115 (42), pp.10654-10659 (2018). DOI: 10.1073/pnas.1809392115. Download PDF reprint
O.L. Dollerup, B.Christensen, M. Svart, M.S. Schmidt, K. Sulek, S. Ringgaard, H. Stødkilde-Jørgensen, N. Møller, C. Brenner, J.T. Treebak &N. Jessen, "A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects," Am J Clin Nutr., v.108(2), pp. 343-353 (2018). DOI: 10.1093/ajcn/nqy132. Download PDF reprint
N. Diguet, S.A.J. Trammell, C. Tannous, R. Deloux, J. Piquereau, N. Mougenot, A. Gouge, M. Gressette, B. Manoury, J. Blanc, M. Breton, J.F. Decaux, G. Lavery, I. Baczkó, J. Zoll, A. Garnier, Z. Li, C. Brenner & M. Mericskay, "Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy," Circulation, v. 137(21), pp. 2256-2273 (2018). DOI: 10.1161/CIRCULATIONAHA.116.026099. Download PDF reprint
M.V. Hamity, S.R. White, R.Y. Walder, M.S. Schmidt, C. Brenner & D.L. Hammond, “Nicotinamide Riboside, a Form of Vitamin B3 and NAD+ Precursor, Relieves the Nociceptive and Aversive Dimensions of Paclitaxel-induced Peripheral Neuropathy in Female Rats,” Pain, v. 158, pp. 962–972 (2017). DOI:10.1097/j.pain.0000000000000862. Download PDF reprint
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." Nat Commun. v. 7, pp. 13103 (2016). 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." Nat Commun. v. 7, pp. 12948 (2016). DOI: 10.1038/ncomms12948. Download pdf 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
C. Brenner, "Why Is Mom Stressed: Homeorhesis as the Potential Problem and Nicotinamide Riboside as the Potential Solution," Journal of Experimental Neuroscience v. 13, pp. 1-3 (2019). DOI: 10.1177/1179069519869679. Download PDF reprint
N.R. Fons, R.K. Sundaram, G.A. Breuer, S. Peng, R.L. McLean, A.N. Kalathil, M.S. Schmidt, D.M. Carvalho, A. Mackay, C. Jones, A.M. Carcaboso, J. Nazarian, M.E. Berens, C. Brenner, & R.S. Bindra., "PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma," Nature Communications, v. 10, 3790 (2019). DOI: 10.1038/s41467-019-11732-6. Download PDFreprint
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- Molecular & Cellular Biology Ph.D. Program
- Genetics Ph.D. Program
- Holden Comprehensive Cancer Center
- Center for Biocatalysis and Bioprocessing