Charles Brenner

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Charles Brenner
Born(1961-10-30)October 30, 1961
NationalityUSA
Alma materWesleyan University (B.A.)
Stanford University (Ph.D)
Brandeis University (Post-Doctoral)
Known forDiscovery and characterization of nicotinamide riboside as a vitamin
AwardsWilliam E.M. Lands Lectureship
Fellow of the American Association for the Advancement of Science
Beckman Young Investigators Award[1]
Basil O'Connor Award from the March of Dimes Birth Defects Foundation
New Investigator Award in the Pharmacological Sciences from the Burroughs Wellcome Fund
ASBMB Award for Exemplary Contributions to Education
Mary Swartz Rose Senior Investigator Award from the American Society for Nutrition[2]
Scientific career
FieldsEnzymology
Metabolism
InstitutionsCity of Hope National Medical Center
University of Iowa
Dartmouth Medical School
Thomas Jefferson University
ThesisSpecificity and Activity of the Kex2 Protease: From Yeast Genetics to Enzyme Kinetics (1993)
Doctoral advisorRobert S. Fuller
Other academic advisorsGregory A. Petsko
Dagmar Ringe
InfluencesArthur Kornberg
Websitebrennerlab.net

Charles Brenner born October 30, 1961 is the chair of the new Department of Diabetes & Cancer Metabolism at the Beckman Research Institute of the City of Hope National Medical Center.[3] He is a major contributor to work on nicotinamide adenine dinucleotide metabolism, who discovered the eukaryotic nicotinamide riboside (NR) kinase pathway.[4]

Education and career[edit]

Brenner is a graduate of Wesleyan University and a veteran of biotechnology companies, having worked at Chiron Corporation and DNAX Research Institute, prior to graduate school at Stanford University School of Medicine. Brenner conducted post-doctoral research at Brandeis University with Gregory Petsko and then took his first academic position at Thomas Jefferson University in 1996, moving to Dartmouth Medical School in 2003, where he served as Associate Director for Basic Sciences at Norris Cotton Cancer Center. He served as chair of biochemistry at University of Iowa from 2009 to 2020.[5]

Research contributions[edit]

Brenner has made multiple contributions to molecular biology and biochemistry, beginning with purification and characterization of the Kex2 proprotein convertase at Stanford.[6] He has been funded by agencies including the Leukemia & Lymphoma Society, the March of Dimes, the Burroughs Wellcome Fund, the Beckman Foundation, the Lung Cancer Research Foundation, the National Institutes of Health, and the National Science Foundation. Significant research projects include molecular dissection of the function of the FHIT tumor suppressor gene,[7][8] characterization and inhibition of DNA methylation,[9][10][11] and discovery of new steps in nicotinamide adenine dinucleotide metabolism.

Notably, the Brenner laboratory discovered that yeast and humans use nicotinamide riboside to make NAD+,[4][12] for which Brenner was recognized with a William E.M. Lands lectureship at University of Michigan. Dr. Brenner developed targeted, quantitative analysis of the NAD+ metabolome[13] and made fundamental contributions to NAD metabolism including discovery of nicotinic acid riboside-dependent NAD synthesis,[14] elucidating the mechanism of synthesis of nicotinic acid adenine dinucleotide phosphate,[15] and discovering multiple conditions in which NAD metabolism is dysregulated in disease.[16][17][18][19][20][21][22][23]

Brenner is also active in translating NR technologies to treat and prevent human conditions that disturb the NAD system including cancer,[17] diabetic and chemotherapeutic peripheral neuropathy,[18][19] heart failure,[16] central brain injury,[20] inflammation,[21] mitochondrial myopathy[22] and coronavirus infection.[23] Brenner's work included the first human trial of NR, which demonstrated safe oral availability as an NAD+ precursor.[24] Though Brenner was the first to show that NR increases SIR2 activity and can extend yeast lifespan,[12] his work has not emphasized sirtuins or nonspecific anti-aging claims and instead emphasizes how NR repairs metabolic stresses that dysregulate NAD+[16][20] and NADPH.[19] He recently showed that rodent postpartum mothers are under severe metabolic stress to their NAD system and that supplementing such mothers with NR increases maternal weight loss, advances juvenile development and provides long lasting neurodevelopmental advantages into adulthood.[25][26][27]

Brenner is author of more than 140 publications and was the senior editor of the 2004 book, Oncogenomics: Molecular Approaches to Cancer.[28]

Educational contributions[edit]

In 2012, Brenner was asked by the President of the American Society for Biochemistry and Molecular Biology to develop pre-medical curriculum recommendations that would be consistent with a revised MCAT examination.[29] These recommendations, which include development of inorganic, organic and biochemistry coursework that is more geared toward the chemistry of bioorganic functional groups, have been further refined in academic journals.[30][31] Brenner's work in this area was recognized by the 2016 ASBMB Award for Exemplary Contributions to Education.[32]

Industrial collaborations[edit]

Brenner is a former member of the Scientific Advisory Board of Sirtris Pharmaceuticals.[33] He is the founder of NRomics and was a co-founder of ProHeathspan prior to its acquisition by ChromaDex, for which he serves as member of the scientific advisory board and chief scientific advisor.[34]

Monograph[edit]

  • Charles Brenner and David Duggan (2004) Oncogenomics: Molecular Approaches to Cancer. John Wiley & Sons, Hoboken, NJ. ISBN 0-471-22592-4

References[edit]

  1. ^ "Charles Brenner". Arnold and Mabel Beckman Foundation. Archived from the original on 2 August 2018. Retrieved 1 August 2018.
  2. ^ https://www.biospace.com/article/releases/chromadex-chief-scientific-advisor-dr-charles-brenner-receives-2020-national-scientific-achievement-award-from-the-american-society-for-nutrition/. Missing or empty |title= (help)
  3. ^ "Awards for Regev and Gierasch; new job for Brenner". www.asbmb.org. Retrieved 2020-07-30.
  4. ^ a b Bieganowski, P; Brenner, C (2004). "Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+ in Fungi and Humans". Cell. 117 (4): 495–502. doi:10.1016/S0092-8674(04)00416-7. PMID 15137942. S2CID 4642295.
  5. ^ "Charles Brenner's CV". Retrieved 2020-07-30.
  6. ^ Brenner, C; Fuller, RS (1992). "Structural and Enzymatic Characterization of a Purified Prohormone-Processing Enzyme: Secreted, Soluble Kex2 Protease". Proc. Natl. Acad. Sci. 89 (3): 922–926. Bibcode:1992PNAS...89..922B. doi:10.1073/pnas.89.3.922. PMC 48357. PMID 1736307.
  7. ^ Draganescu, A; Hodawadekar, SC; Gee, KR; Brenner, C (2000). "Fhit-Nucleotide Specificity Probed with Novel Fluorescent and Fluorogenic Substrates". J. Biol. Chem. 275 (7): 4555–4560. doi:10.1074/jbc.275.7.4555. PMC 2556043. PMID 10671479.
  8. ^ Trapasso, F; et al. (2003). "Designed FHIT Alleles Establish that Fhit-Induced Apoptosis in Cancer Cells is Limited by Substrate-Binding". Proc. Natl. Acad. Sci. 100 (4): 1592–1597. Bibcode:2003PNAS..100.1592T. doi:10.1073/pnas.0437915100. PMC 149877. PMID 12574506.
  9. ^ Syeda, F; Fagan, RL; Wean, M; Avvakumov, GV; Walker, JR; Xue, S; Dhe-Paganon S; Brenner, C (2011). "The Replication Focus Targeting Sequence (RFTS) Domain is a DNA-Competitive Inhibitor of Dnmt1". J. Biol. Chem. 286 (17): 15344–15351. doi:10.1074/jbc.M110.209882. PMC 3083197. PMID 21389349.
  10. ^ Fagan, RL; Cryderman, DE; Kopelovich, L; Wallrath, LL; Brenner, C (2013). "Laccaic Acid A Is a Direct, DNA-competitive Inhibitor of DNA Methyltransferase 1". J. Biol. Chem. 288 (33): 23858–23867. doi:10.1074/jbc.M113.480517. PMC 3745332. PMID 23839987.
  11. ^ Wu, B-K; Brenner, C (2014). "Suppression of TET1-Dependent DNA Demethylation Is Essential for KRAS-Mediated Transformation". Cell Reports. 9 (5): 1827–1840. doi:10.1016/j.celrep.2014.10.063. PMC 4268240. PMID 25466250.
  12. ^ a b Belenky, P; et al. (2007). "Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+". Cell. 129 (3): 473–484. doi:10.1016/j.cell.2007.03.024. PMID 17482543. S2CID 4661723.
  13. ^ Trammell, SAJ; Brenner, C (2013). "Targeted, LCMS-based Metabolomics for Quantitative Measurement of NAD(+) Metabolites". Comput Struct Biotechnol J. 4 (5): e201301012. doi:10.5936/csbj.201301012. PMC 3962138. PMID 24688693.
  14. ^ Tempel, Wolfram; Rabeh, Wael M.; Bogan, Katrina L.; Belenky, Peter; Wojcik, Marzena; Seidle, Heather F.; Nedyalkova, Lyudmila; Yang, Tianle; Sauve, Anthony A.; Park, Hee-Won; Brenner, Charles (2007-10-02). "Nicotinamide riboside kinase structures reveal new pathways to NAD+". PLOS Biology. 5 (10): e263. doi:10.1371/journal.pbio.0050263. ISSN 1545-7885. PMC 1994991. PMID 17914902.
  15. ^ Nam, Tae-Sik; Park, Dae-Ryoung; Rah, So-Young; Woo, Tae-Gyu; Chung, Hun Taeg; Brenner, Charles; Kim, Uh-Hyun (2020). "Interleukin-8 drives CD38 to form NAADP from NADP+ and NAAD in the endolysosomes to mobilize Ca2+ and effect cell migration". The FASEB Journal. n/a (n/a): 12565–12576. doi:10.1096/fj.202001249R. ISSN 1530-6860. PMID 32717131.
  16. ^ a b c Diguet, Nicolas; Trammell, Samuel A. J.; Tannous, Cynthia; Deloux, Robin; Piquereau, Jérôme; Mougenot, Nathalie; Gouge, Anne; Gressette, Mélanie; Manoury, Boris (2017-12-07). "Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy". Circulation. 137 (21): 2256–2273. doi:10.1161/CIRCULATIONAHA.116.026099. ISSN 1524-4539. PMC 6954688. PMID 29217642.
  17. ^ a b Fons, Nathan R.; Sundaram, Ranjini K.; Breuer, Gregory A.; Peng, Sen; McLean, Ryan L.; Kalathil, Aravind N.; Schmidt, Mark S.; Carvalho, Diana M.; Mackay, Alan; Jones, Chris; Carcaboso, Ángel M. (2019-08-22). "PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma". Nature Communications. 10 (1): 3790. Bibcode:2019NatCo..10.3790F. doi:10.1038/s41467-019-11732-6. ISSN 2041-1723. PMC 6706443. PMID 31439867.
  18. ^ a b New Vitamin May Relieve a Painful Problem Archived 2013-08-19 at the Wayback Machine Focus April 20, 2008
  19. ^ a b c Trammell, SAJ; Weidemann, BJ; Chadda, A; Yorek, MS; Holmes, A; Coppey, LJ; Obrosov, A; Kardon, RH; Yorek, MA; Brenner, C (2016). "Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice". Scientific Reports. 6: 26933. Bibcode:2016NatSR...626933T. doi:10.1038/srep26933. PMC 4882590. PMID 27230286.
  20. ^ a b c Vaur, Pauline; Brugg, Bernard; Mericskay, Mathias; Li, Zhenlin; Schmidt, Mark S.; Vivien, Denis; Orset, Cyrille; Jacotot, Etienne; Brenner, Charles (December 2017). "Nicotinamide riboside, a form of vitamin B3, protects against excitotoxicity-induced axonal degeneration". FASEB Journal. 31 (12): 5440–5452. doi:10.1096/fj.201700221RR. ISSN 1530-6860. PMID 28842432.
  21. ^ a b Covarrubias, Anthony J.; Kale, Abhijit; Perrone, Rosalba; Lopez-Dominguez, Jose Alberto; Pisco, Angela Oliveira; Kasler, Herbert G.; Schmidt, Mark S.; Heckenbach, Indra; Kwok, Ryan; Wiley, Christopher D.; Wong, Hoi-Shan (November 2020). "Senescent cells promote tissue NAD + decline during ageing via the activation of CD38 + macrophages". Nature Metabolism. 2 (11): 1265–1283. doi:10.1038/s42255-020-00305-3. ISSN 2522-5812. PMID 33199924.
  22. ^ a b Pirinen, Eija; Auranen, Mari; Khan, Nahid A.; Brilhante, Virginia; Urho, Niina; Pessia, Alberto; Hakkarainen, Antti; Kuula, Juho; Heinonen, Ulla; Schmidt, Mark S.; Haimilahti, Kimmo (2020-06-02). "Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy". Cell Metabolism. 31 (6): 1078–1090.e5. doi:10.1016/j.cmet.2020.04.008. ISSN 1550-4131. PMID 32386566.
  23. ^ a b Heer, Collin D.; Sanderson, Daniel J.; Voth, Lynden S.; Alhammad, Yousef M. O.; Schmidt, Mark S.; Trammell, Samuel A. J.; Perlman, Stanley; Cohen, Michael S.; Fehr, Anthony R.; Brenner, Charles (2020-10-13). "Coronavirus infection and PARP expression dysregulate the NAD Metabolome: an actionable component of innate immunity". Journal of Biological Chemistry. 295 (52): 17986–17996. doi:10.1074/jbc.RA120.015138. PMID 33051211.
  24. ^ Trammell, S.A.J.; et al. (2016). "Nicotinamide riboside is uniquely and orally bioavailable in mice and humans". Nat. Commun. 7: 12948. Bibcode:2016NatCo...712948T. doi:10.1038/ncomms12948. PMC 5062546. PMID 27721479.
  25. ^ Ear, Po Hien; Chadda, Ankita; Gumusoglu, Serena B.; Schmidt, Mark S.; Vogeler, Sophia; Malicoat, Johnny; Kadel, Jacob; Moore, Michelle M.; Migaud, Marie E. (January 2019). "Maternal Nicotinamide Riboside Enhances Postpartum Weight Loss, Juvenile Offspring Development, and Neurogenesis of Adult Offspring". Cell Reports. 26 (4): 969–983.e4. doi:10.1016/j.celrep.2019.01.007. ISSN 2211-1247. PMID 30673618.
  26. ^ Cell Press, Combating Postpartum Metabolic Stress/Cell Reports, Jan. 22, 2019 (Vol. 22, Issue 4), retrieved 2019-01-26
  27. ^ "Supplement makes (mouse) moms' milk better; pups benefit for life". medicalxpress.com. Retrieved 2019-01-26..
  28. ^ Brenner, Charles (2004). Oncogenomics: Molecular Approaches to Cancer. Hoboken: John Wiley & Sons. ISBN 0471225924.
  29. ^ Response to the new MCAT: ASBMB premedical curriculum recommendations Archived 2012-06-03 at the Wayback Machine ASBMB Today, March 2012
  30. ^ Brenner, C (2013). "Changes in Chemistry and Biochemistry Education: Creative Responses to MCAT Revisions in the Age of the Genome". Biochemistry and Molecular Biology Education. 41 (1): 1–4. doi:10.1002/bmb.20653. PMID 23281187. S2CID 4659938.
  31. ^ Brenner, C (2013). "Rethinking Premedical and Health Professional Curricula in Light of MCAT 2015". J. Chem. Educ. 90 (7): 807–812. Bibcode:2013JChEd..90..807B. doi:10.1021/ed4002738. S2CID 98274150.
  32. ^ "Brenner receives ASBMB Award for Exemplary Contributions to Education". University of Iowa. August 20, 2015. Retrieved 1 August 2018.
  33. ^ Belenky, Peter; Bogan, Katrina L.; Brenner, Charles (January 2007). "NAD+ metabolism in health and disease". Trends in Biochemical Sciences. 32 (1): 12–19. doi:10.1016/j.tibs.2006.11.006. PMID 17161604. Retrieved 1 August 2018.
  34. ^ "Charles Brenner Ph.D." Bloomberg. Retrieved 1 August 2018.

External links[edit]