Charles Brenner, PhD

Biography

Dr. Charles Brenner is a metabolism researcher who discovered the eukaryotic nicotinamide riboside (NR) kinase biosynthetic pathway to nicotinamide adenine dinucleotide (NAD).  In addition to discovering biosynthetic routes to NAD from NR and nicotinic acid riboside, Dr. Brenner developed quantitative targeted analysis of the NAD metabolome, established the role of NR in protection against nonalcoholic fatty liver, diabetic and chemotherapeutic neuropathy, heart failure and other conditions in which the NAD metabolome is dysregulated by metabolic stress.  Dr. Brenner further discovered that the NAD system is disturbed during postpartum and that NR boosts lactation, maternal weight loss and offspring development.  He performed the first clinical trial of NR, which established safe oral availability of NR to people, and continues to probe NAD-dependent mechanisms in health and disease in model systems in addition to developing clinical assessment of NR activities in human populations in diseases and conditions of metabolic stress.

Publications

P. Bieganowski & C. Brenner, “Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+ in Fungi and Humans,” Cell, v. 117, pp. 495-502 (2004).

C. Brenner, “Evolution of NAD Biosynthetic Enzymes,” Structure, v. 13, pp. 1239-1240 (2005).

P. Bieganowski, H.F. Seidle, M. Wojcik & C. Brenner, “Synthetic Lethal and Biochemical Analyses of NAD and NADH Kinases in Saccharomyces cerevisiae Establish Separation of Cellular Functions,” J Biol Chem, v. 281, pp. 22439-22445 (2006).

M. Wojcik, H.F. Seidle, P. Bieganowski & C. Brenner, “Glutamine-Dependent NAD+ synthetase: How a Two-Domain, Three-Substrate Enzyme Avoids Waste,” J Biol Chem, v. 281, pp. 33395-33402 (2006).

P. Belenky, K.L. Bogan & C. Brenner, “NAD+ Metabolism in Health and Disease,” Trends in Biochemical Sciences, v. 32, pp. 12-19 (2007).

C.L. Linster, T.A. Gomez, K.C. Christensen, L.N. Adler, B.D. Young, C. Brenner & S.G. Clarke, “Arabidopis VTC2 Encodes GDP-L-Galactose Phosphorylase, the Last Unknown Enzyme in the Smirnoff-Wheeler Pathway to Ascorbic Acid in Plants,” J Biol Chem, v. 282, pp. 18879-18885 (2007).

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).

W. Tempel, W.M. Rabeh, K.L. Bogan, P. Belenky, M. Wojcik, H.F. Seidle, L. Nedyalkova, T. Yang, A.A. Sauve, H.-W. Park & C. Brenner, “Nicotinamide Riboside Kinase Structures Reveal New Pathways to NAD+,” PLoS Biology, v. 5, issue 10, e263 (2007).

P.A. Belenky, T.G. Mogu & C. Brenner, “S. cerevisiae YOR071C Encodes the High Affinity Nicotinamide Riboside Transporter, Nrt1,” J Biol Chem, v. 283, pp. 8075-8079 (2008).

K.L. Bogan & C. Brenner, “Nicotinic Acid, Nicotinamide, and Nicotinamide Riboside: A Molecular Evaluation of NAD+ Precursor Vitamins in Human Nutrition,” Ann Review Nutrition, v. 28, pp. 115-130 (2008).

C.L. Linster, L.T. Adler, K. Webb, K.C. Christensen, C. Brenner & S.G. Clarke, “A Second GDP-L-Galactose Phosphorylase in Arabidopsis en Route to Vitamin C: Covalent Intermediate and Substrate Requirements for the Conserved Reaction,” J Biol Chem, v. 283, pp. 18483-18492 (2008).

P. Belenky, K.C. Christensen, F. Gazzaniga, A.A. Pletnev & C. Brenner, “Nicotinamide Riboside and Nicotinic Acid Riboside Salvage in Fungi and Mammals: Quantitative Basis for Urh1 and Purine Nucleoside Phosphorylase Function in NAD+ Metabolism,” J Biol Chem, v. 284, pp. 158-164 (2009).

P. Bieganowski & C. Brenner, “Nicotinamide Riboside Kinase Compositions and Methods for Using the Same,”Australian Patent 2005211773, issued June 1, 2009.

F. Gazzaniga, R. Stebbins, S. Z. Chang, M.A. McPeek & C.Brenner, “Microbial NAD Metabolism: Lessons from Comparative Genomics, “Microbiol Mol Biol Rev, v. 73, pp. 529-541 (2009).

K.L. Bogan, C. Evans, P. Belenky, P. Song, C.F. Burant, R.T. Kennedy & C. Brenner, ” Identification of Isn1 and Sdt1 as Glucose and Vitamin-regulated NMN and NaMN 5′-nucleotidases Responsible for Production of Nicotinamide Riboside and Nicotinic Acid Riboside,” J Biol Chem, v. 284, pp. 34861-34869 (2009).

C. Evans, K.L. Bogan, P. Song, C.F. Burant, R.T. Kennedy & C. Brenner, “NAD+ Metabolite Levels as a Function of Vitamins and Calorie Restriction: Evidence for Different Mechanisms of Longevity,” BMC Chem Biol, v. 10, 2 (2010).

K.L. Bogan & C. Brenner, “5′-Nucleotidases and their New Roles in NAD+ and Phosphate Metabolism,” New Journal of Chemistry, v. 34, pp. 845-853 (2010).

C. Brenner. “On the Nonspecific Degradation of NAD+ to Nicotinamide Riboside,” JBC, v. 286, p. le5 (2011).

P. Belenky, R. Stebbins, K.L. Bogan, C.R. Evans & C. Brenner, “Nrt1 and Tna1-Independent Export of NAD+ Precursor Vitamins Promotes NAD+ Homeostasis and Allows Engineering of Vitamin Production,” PLoS ONE, v. 6, p. e19710 (2011).

C. Brenner, P. Belenky & K.L. Bogan, “Yeast Strain and Method for Using the Same to Produce Nicotinamide Riboside,” US Patent 8,114,626, issued February 14, 2012.

R.R. Midtkandal, P. Redpath, S.A.J. Trammell, S.J.F. Macdonald, C. Brenner & M.E. Migaud, “Novel synthetic route to the C-nucleoside, 2-deoxy benzamide riboside,” Bioorganic & Medicinal Chemistry Letters v. 22, pp. 5204-7 (2012).

C. Brenner, “Nicotinamide riboside kinase compositions and methods for using the same,” US Patent 8,197,807, issued June 12, 2012.

C. Brenner, “Nicotinamide riboside kinase compositions and methods for using the same,” US Patent 8,383,086, issued February 26, 2013.

K.L. Bogan & C. Brenner, “Biochemistry: Niacin/NAD(P),” Encyclopedia of Biological Chemistry, W.J. Lennarz & M.D. Lane, eds., v. 3, pp.172-178, (2013), Waltham, MA: Academic Press.

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.

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).

S-C. Mei & C. Brenner, “NAD as a Genotype-Specific Drug Target” Chemistry & Biology, v. 20, pp. 1307-1308 (2013).

C. Brenner, “Metabolism: Targeting a fat-accumulation gene” Nature, v. 508, pp. 194-195 (2014). DOI: 10.1038/508194a.

S.-C. Mei & C. Brenner, “Quantification of Protein Copy Number in Yeast: the NAD+ Metabolome,” PLoS One v. 9, e106496 (2014). DOI: 10.1371/journal.pone.0106496.

C. Brenner, “Boosting NAD to Spare Hearing,” Cell Metabolism, v. 21, pp.926-927 (2014). DOI: 10.1016/j.cmet.2014.11.015.

S.-C. Mei & C. Brenner, “Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous,” PLoS Biology, v. 13, e1002048 (2015).

S.A.J. Trammell & C. Brenner, “NNMT: A Bad Actor in Fat Makes Good in Liver,” Cell Metabolism, v. 22, pp. 200-201 (2015). DOI:10.1016/j.cmet.2015.07.017.

S.A.J. Trammell, L. Yu, P. Redpath, M.E. Migaud & C. Brenner, “Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk,” The Journal of Nutrition, v. 146, pp. 957-963 (2016). DOI: 10.3945/jn.116.230078.

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.

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.

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.

J.L. Wilsbacher, M. Cheng, D. Cheng, S.A.J. Trammell, Y. Shi, J. Guo, S.L. Koeniger, P.J. Kovar, Y. He, S. Jagadeeswaran, H.R. Heyman, B.K. Sorensen, R.F. Clark, T.M. Hansen, K.L. Longenecker, D. Raich, A.V. Korepanova, D.L. Towne, V.C. Abraham, H. Tang, S.M. McLoughlin, M.L. Curtin, M.R. Michaelides, D. Maag, F.G. Buchanan, W. Gao, S.H. Rosenberg, C. Brenner & C. Tse, “Discovery and Characterization of Novel, Orally Bioavailable Non-substrate and Substrate NAMPT Inhibitors,” Molecular Cancer Therapeutics, v. 16, pp. 1236-1245 (2017). DOI:10.1158/1535-7163.MCT-16-0819.

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.

R. Fletcher, J. Ratajczak, C.L. Doig, L.A. Oakey, R.Callingham, G. da Silva Xavier, A. Garten, Y.S. Elhassan, P. Redpath, M.E. Migaud, A. Philp, C. Brenner, C. Canto & G.G. Lavery, “Nicotinamide Riboside Kinases Display Redundancy in Mediating Nicotinamide Mononucleotide and Nicotinamide Riboside Metabolism in Skeletal Muscle Cells,” Molecular Metabolism, v. 6 (2017). DOI: 10.1016/j.molmet.2017.05.011.

P. Vaur, B. Brugg, M. Mericskay, Z. Li, M.S. Schmidt, D. Vivien, C. Orset, E. Jacotot, C. Brenner & E. Duplus, “Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration,” FASEB Journal (2017). DOI: 10.1096/fj.201700221RR.

S. Sato, G. Solanas, F.O. Peixoto, L. Bee, A. Symeonidi, M.S. Schmidt, C. Brenner, S. Masri, S.A. Benitah & P. Sassone-Corsi, “Circadian Reprogramming Identifies Metabolic Pathways of Aging,” Cell, v. 170(4), pp. 664-677 (2017). DOI: 10.1016/j.cell.2017.07.042.

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.

D. Fangmann, E.M. Theismann, K. Türk, D.M. Schulte, I. Relling, K. Hartmann, J.K. Keppler, J.R. Knipp, A. Rehman, F.A. Heinsen, A. Franke, L. Lenk, S. Freitag-Wolf, E. Appel, S. Gorb, C. Brenner, D. Seegert, G.H. Waetzig, P. Rosenstiel, S. Schreiber, K. Schwarz & M. Laudes, “Targeted Microbiome Intervention by Microencapsulated Delayed-Release Niacin Beneficially Affects Insulin Sensitivity in Humans,” Diabetes Care, v. 41(3), pp. 398-405 (2018). DOI: 10.2337/dc17-1967.

D.S. Matasic, C. Brenner & B. London, “Emerging Potential Benefits of Modulating NAD+ Metabolism in Cardiovascular Disease,” Am J Physiol Heart Circ Physiol, v. 314(4), pp. H839-H852 (2018). DOI: 10.1152/ajpheart.00409.2017.

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.

S.J. Mitchell, M. Bernier, M.A. Aon, S. Cortassa, E.Y. Kim, E.F. Fang, H.H. Palacios, Ali A1, I. Navas-Enamorado, A. Di Francesco, T.A. Kaiser, T.B. Waltz, N. Zhang, J.L. Ellis, P.J. Elliott, D.W. Frederick, V.A. Bohr, M. S. Schmidt, C. Brenner, D.A. Sinclair, A. A. Sauve, J.A. Baur & R. de Cabo, “Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice,” Cell Metab. 27(3):667-676.e4 (2018). DOI: 10.1016/j.cmet.2018.02.001.

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.

C. Brenner & A.C. Boileau, “Pterostilbene Raises Low Density Lipoprotein Cholesterol in People,” Clinical Nutrition. v.38(1), pp.480-481 (2019), DOI:10.1016/j.clnu.2018.10.007.

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.

W. Shi, M.A. Hegeman, A. Doncheva, I. van der Stelt, M. Bekkenkamp-Grovenstein, E. M. van Schothorst, C.Brenner, V. C. J. de Boer & J. Keijer, “Transcriptional Response of White Adipose Tissue to Withdrawal of Vitamin B3,” Mol Nutr Food Res., in press, 2019. DOI: 10.1002/mnfr.201801100.

A.J. Covarrubias, J. A. Lopez-Dominguez, R. Perrone, A. Kale, J. Newman, S. S. Iyer, M. S. Schmidt, H. G. Kasler, K.-O. Shin, Y.-M. Lee, I. Ben-Sahra, M. Ott, C. Brenner, J.Campisi & E. Verdin, “Aging-related inflammation driven by cellular senescence enhances NAD consumption via activation of CD38+ macrophages,” 2019.

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