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==Research contributions==
==Research contributions==
Brenner has made multiple contributions to molecular biology and biochemistry, beginning with purification and characterization of the Kex2 [[proprotein convertase]] at Stanford.{{cn|date=February 2023}} 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]], the [[National Science Foundation]] and the [[Bill & Melinda Gates Foundation]]. Significant research projects include molecular dissection of the function of the [[FHIT]] tumor suppressor gene,<ref>{{cite journal | doi = 10.1074/jbc.275.7.4555 |author1=Draganescu, A |author2=Hodawadekar, SC |author3=Gee, KR |author4=Brenner, C | title = Fhit-Nucleotide Specificity Probed with Novel Fluorescent and Fluorogenic Substrates | journal = J. Biol. Chem. | volume = 275 | pages = 4555&ndash;4560 | year = 2000 | pmid = 10671479 | issue = 7 | pmc = 2556043 |doi-access=free }}</ref><ref>{{cite journal | author = Trapasso, F | title = Designed FHIT Alleles Establish that Fhit-Induced Apoptosis in Cancer Cells is Limited by Substrate-Binding | journal = Proc. Natl. Acad. Sci. | volume = 100 | pages = 1592&ndash;1597 | year = 2003 | pmid = 12574506 | issue = 4 | doi = 10.1073/pnas.0437915100 | pmc = 149877 |display-authors=etal| bibcode = 2003PNAS..100.1592T | doi-access = free }}</ref> characterization and inhibition of [[DNA methylation]],<ref>{{cite journal | author = Syeda, F | author2 = Fagan, RL | author3 = Wean, M | author4 = Avvakumov, GV | author5 = Walker, JR | author6 = Xue, S | author7 = Dhe-Paganon S | author8 = Brenner, C | title = The Replication Focus Targeting Sequence (RFTS) Domain is a DNA-Competitive Inhibitor of Dnmt1 | journal = J. Biol. Chem. | volume = 286 | pages = 15344&ndash;15351 | year = 2011 | pmid = 21389349 | issue = 17 | pmc = 3083197 | doi=10.1074/jbc.M110.209882| doi-access = free }}</ref><ref>{{cite journal |author1=Fagan, RL |author2=Cryderman, DE |author3=Kopelovich, L |author4=Wallrath, LL |author5=Brenner, C | title = Laccaic Acid A Is a Direct, DNA-competitive Inhibitor of DNA Methyltransferase 1 | journal = J. Biol. Chem. | volume = 288 | pages = 23858&ndash;23867 | year = 2013 | pmid = 23839987 | doi=10.1074/jbc.M113.480517 | issue=33 | pmc=3745332|doi-access=free }}</ref><ref>{{cite journal |author1=Wu, B-K |author2=Brenner, C | title = Suppression of TET1-Dependent DNA Demethylation Is Essential for KRAS-Mediated Transformation | journal = Cell Reports | volume = 9 |issue=5 | year = 2014 | doi = 10.1016/j.celrep.2014.10.063 | pages=1827–1840 | pmid=25466250 | pmc=4268240}}</ref> and discovery of new steps in [[nicotinamide adenine dinucleotide]] metabolism.
Brenner has made multiple contributions to molecular biology and biochemistry, beginning with purification and characterization of the Kex2 [[proprotein convertase]] at Stanford.<ref name="Nakayama">{{cite journal |last1=Nakayama |first1=Kazuhisa |title=Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins |journal=Biochemical Journal |date=1 November 1997 |volume=327 |issue=3 |pages=625–635 |doi=10.1042/bj3270625 |url=https://doi.org/10.1042/bj3270625 |access-date=6 February 2023}}</ref><ref name="Sreenivas">{{cite journal |last1=Sreenivas |first1=Suma |last2=Krishnaiah |first2=Sateesh M. |last3=Govindappa |first3=Nagaraja |last4=Basavaraju |first4=Yogesh |last5=Kanojia |first5=Komal |last6=Mallikarjun |first6=Niveditha |last7=Natarajan |first7=Jayaprakash |last8=Chatterjee |first8=Amarnath |last9=Sastry |first9=Kedarnath N. |title=Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris |journal=Applied Microbiology and Biotechnology |date=January 2015 |volume=99 |issue=1 |pages=327–336 |doi=10.1007/s00253-014-6052-5 |access-date=6 February 2023}}</ref> 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]], the [[National Science Foundation]] and the [[Bill & Melinda Gates Foundation]]. Significant research projects include molecular dissection of the function of the [[FHIT]] tumor suppressor gene,<ref>{{cite journal | doi = 10.1074/jbc.275.7.4555 |author1=Draganescu, A |author2=Hodawadekar, SC |author3=Gee, KR |author4=Brenner, C | title = Fhit-Nucleotide Specificity Probed with Novel Fluorescent and Fluorogenic Substrates | journal = J. Biol. Chem. | volume = 275 | pages = 4555&ndash;4560 | year = 2000 | pmid = 10671479 | issue = 7 | pmc = 2556043 |doi-access=free }}</ref><ref>{{cite journal | author = Trapasso, F | title = Designed FHIT Alleles Establish that Fhit-Induced Apoptosis in Cancer Cells is Limited by Substrate-Binding | journal = Proc. Natl. Acad. Sci. | volume = 100 | pages = 1592&ndash;1597 | year = 2003 | pmid = 12574506 | issue = 4 | doi = 10.1073/pnas.0437915100 | pmc = 149877 |display-authors=etal| bibcode = 2003PNAS..100.1592T | doi-access = free }}</ref> characterization and inhibition of [[DNA methylation]],<ref>{{cite journal | author = Syeda, F | author2 = Fagan, RL | author3 = Wean, M | author4 = Avvakumov, GV | author5 = Walker, JR | author6 = Xue, S | author7 = Dhe-Paganon S | author8 = Brenner, C | title = The Replication Focus Targeting Sequence (RFTS) Domain is a DNA-Competitive Inhibitor of Dnmt1 | journal = J. Biol. Chem. | volume = 286 | pages = 15344&ndash;15351 | year = 2011 | pmid = 21389349 | issue = 17 | pmc = 3083197 | doi=10.1074/jbc.M110.209882| doi-access = free }}</ref><ref>{{cite journal |author1=Fagan, RL |author2=Cryderman, DE |author3=Kopelovich, L |author4=Wallrath, LL |author5=Brenner, C | title = Laccaic Acid A Is a Direct, DNA-competitive Inhibitor of DNA Methyltransferase 1 | journal = J. Biol. Chem. | volume = 288 | pages = 23858&ndash;23867 | year = 2013 | pmid = 23839987 | doi=10.1074/jbc.M113.480517 | issue=33 | pmc=3745332|doi-access=free }}</ref><ref>{{cite journal |author1=Wu, B-K |author2=Brenner, C | title = Suppression of TET1-Dependent DNA Demethylation Is Essential for KRAS-Mediated Transformation | journal = Cell Reports | volume = 9 |issue=5 | year = 2014 | doi = 10.1016/j.celrep.2014.10.063 | pages=1827–1840 | pmid=25466250 | pmc=4268240}}</ref> and discovery of new steps in [[nicotinamide adenine dinucleotide]] metabolism.


Notably, the Brenner laboratory discovered that yeast uses [[nicotinamide riboside]] to make NAD+,<ref>{{cite journal |last1=James Theoga Raj |first1=Christol |last2=Lin |first2=Su-Ju |title=Cross-talk in NAD+ metabolism: insights from Saccharomyces cerevisiae |journal=Current Genetics |date=October 2019 |volume=65 |issue=5 |pages=1113–1119 |doi=10.1007/s00294-019-00972-0 |pmid=30993413 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744962/}}</ref><ref name="Bieganowski, P, Brenner, C 2004 495–502">{{cite journal | doi = 10.1016/S0092-8674(04)00416-7 |author1=Bieganowski, P |author2=Brenner, C |s2cid=4642295 | title = Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+ in Fungi and Humans | journal = Cell | volume = 117 | pages = 495&ndash;502 | year = 2004 | pmid = 15137942 | issue = 4 | doi-access = free }}</ref><ref name=":0">{{cite journal | author = Belenky, P | s2cid = 4661723 | title = Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+ | journal = Cell | volume = 129 | pages = 473&ndash;484 | year = 2007 | pmid = 17482543 | issue = 3 | doi = 10.1016/j.cell.2007.03.024 |display-authors=etal| doi-access = free }}</ref> 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<ref>{{cite journal |author1=Trammell, SAJ |author2=Brenner, C | title = Targeted, LCMS-based Metabolomics for Quantitative Measurement of NAD(+) Metabolites | journal = Comput Struct Biotechnol J | volume = 4 |issue=5 | pages = e201301012 | year = 2013 | pmid = 24688693 | doi=10.5936/csbj.201301012 | pmc=3962138}}</ref> and made fundamental contributions to NAD metabolism including discovery of nicotinic acid riboside-dependent NAD synthesis,<ref>{{Cite journal|last1=Tempel|first1=Wolfram|last2=Rabeh|first2=Wael M.|last3=Bogan|first3=Katrina L.|last4=Belenky|first4=Peter|last5=Wojcik|first5=Marzena|last6=Seidle|first6=Heather F.|last7=Nedyalkova|first7=Lyudmila|last8=Yang|first8=Tianle|last9=Sauve|first9=Anthony A.|last10=Park|first10=Hee-Won|last11=Brenner|first11=Charles|date=2007-10-02|title=Nicotinamide riboside kinase structures reveal new pathways to NAD+|journal=PLOS Biology|volume=5|issue=10|pages=e263|doi=10.1371/journal.pbio.0050263|issn=1545-7885|pmc=1994991|pmid=17914902}}</ref> elucidating the mechanism of synthesis of [[nicotinic acid adenine dinucleotide phosphate]],<ref>{{Cite journal|last1=Nam|first1=Tae-Sik|last2=Park|first2=Dae-Ryoung|last3=Rah|first3=So-Young|last4=Woo|first4=Tae-Gyu|last5=Chung|first5=Hun Taeg|last6=Brenner|first6=Charles|last7=Kim|first7=Uh-Hyun|title=Interleukin-8 drives CD38 to form NAADP from NADP+ and NAAD in the endolysosomes to mobilize Ca2+ and effect cell migration|journal=The FASEB Journal|year=2020|volume=34|issue=9|language=en|pages=12565–12576|doi=10.1096/fj.202001249R|pmid=32717131|issn=1530-6860|doi-access=free}}</ref> and discovering multiple conditions in which NAD metabolism is dysregulated in disease.<ref name=":2" /><ref name=":4">{{Cite journal|last1=Fons|first1=Nathan R.|last2=Sundaram|first2=Ranjini K.|last3=Breuer|first3=Gregory A.|last4=Peng|first4=Sen|last5=McLean|first5=Ryan L.|last6=Kalathil|first6=Aravind N.|last7=Schmidt|first7=Mark S.|last8=Carvalho|first8=Diana M.|last9=Mackay|first9=Alan|last10=Jones|first10=Chris|last11=Carcaboso|first11=Ángel M.|date=2019-08-22|title=PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma|journal=Nature Communications|language=en|volume=10|issue=1|page=3790|doi=10.1038/s41467-019-11732-6|pmid=31439867|pmc=6706443|bibcode=2019NatCo..10.3790F|issn=2041-1723}}</ref><ref name=":5" /><ref name=":1" /><ref name=":3" /><ref name=":6">{{Cite journal|last1=Covarrubias|first1=Anthony J.|last2=Kale|first2=Abhijit|last3=Perrone|first3=Rosalba|last4=Lopez-Dominguez|first4=Jose Alberto|last5=Pisco|first5=Angela Oliveira|last6=Kasler|first6=Herbert G.|last7=Schmidt|first7=Mark S.|last8=Heckenbach|first8=Indra|last9=Kwok|first9=Ryan|last10=Wiley|first10=Christopher D.|last11=Wong|first11=Hoi-Shan|date=November 2020|title=Senescent cells promote tissue NAD + decline during ageing via the activation of CD38 + macrophages|url= |journal=Nature Metabolism|language=en|volume=2|issue=11|pages=1265–1283|doi=10.1038/s42255-020-00305-3|pmid=33199924|issn=2522-5812|pmc=7908681}}</ref><ref name=":7">{{Cite journal|last1=Pirinen|first1=Eija|last2=Auranen|first2=Mari|last3=Khan|first3=Nahid A.|last4=Brilhante|first4=Virginia|last5=Urho|first5=Niina|last6=Pessia|first6=Alberto|last7=Hakkarainen|first7=Antti|last8=Kuula|first8=Juho|last9=Heinonen|first9=Ulla|last10=Schmidt|first10=Mark S.|last11=Haimilahti|first11=Kimmo|date=2020-06-02|title=Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy|url=http://www.sciencedirect.com/science/article/pii/S155041312030190X|journal=Cell Metabolism|language=en|volume=31|issue=6|pages=1078–1090.e5|doi=10.1016/j.cmet.2020.04.008|pmid=32386566|issn=1550-4131|hdl=10138/330502|s2cid=218585981|hdl-access=free}}</ref><ref name=":8">{{Cite journal|last1=Heer|first1=Collin D.|last2=Sanderson|first2=Daniel J.|last3=Voth|first3=Lynden S.|last4=Alhammad|first4=Yousef M. O.|last5=Schmidt|first5=Mark S.|last6=Trammell|first6=Samuel A. J.|last7=Perlman|first7=Stanley|last8=Cohen|first8=Michael S.|last9=Fehr|first9=Anthony R.|last10=Brenner|first10=Charles|date=2020-10-13|title=Coronavirus infection and PARP expression dysregulate the NAD Metabolome: an actionable component of innate immunity|url=https://www.jbc.org/content/295/52/17986.short|journal=Journal of Biological Chemistry|volume=295|issue=52|pages=17986–17996|doi=10.1074/jbc.RA120.015138|pmid=33051211|pmc=7834058|doi-access=free}}</ref>
Notably, the Brenner laboratory discovered that yeast uses [[nicotinamide riboside]] to make NAD+,<ref>{{cite journal |last1=James Theoga Raj |first1=Christol |last2=Lin |first2=Su-Ju |title=Cross-talk in NAD+ metabolism: insights from Saccharomyces cerevisiae |journal=Current Genetics |date=October 2019 |volume=65 |issue=5 |pages=1113–1119 |doi=10.1007/s00294-019-00972-0 |pmid=30993413 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744962/}}</ref><ref name="Bieganowski, P, Brenner, C 2004 495–502">{{cite journal | doi = 10.1016/S0092-8674(04)00416-7 |author1=Bieganowski, P |author2=Brenner, C |s2cid=4642295 | title = Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD+ in Fungi and Humans | journal = Cell | volume = 117 | pages = 495&ndash;502 | year = 2004 | pmid = 15137942 | issue = 4 | doi-access = free }}</ref><ref name=":0">{{cite journal | author = Belenky, P | s2cid = 4661723 | title = Nicotinamide Riboside Promotes Sir2 Silencing and Extends Lifespan via Nrk and Urh1/Pnp1/Meu1 Pathways to NAD+ | journal = Cell | volume = 129 | pages = 473&ndash;484 | year = 2007 | pmid = 17482543 | issue = 3 | doi = 10.1016/j.cell.2007.03.024 |display-authors=etal| doi-access = free }}</ref> 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<ref>{{cite journal |author1=Trammell, SAJ |author2=Brenner, C | title = Targeted, LCMS-based Metabolomics for Quantitative Measurement of NAD(+) Metabolites | journal = Comput Struct Biotechnol J | volume = 4 |issue=5 | pages = e201301012 | year = 2013 | pmid = 24688693 | doi=10.5936/csbj.201301012 | pmc=3962138}}</ref> and made fundamental contributions to NAD metabolism including discovery of nicotinic acid riboside-dependent NAD synthesis,<ref>{{Cite journal|last1=Tempel|first1=Wolfram|last2=Rabeh|first2=Wael M.|last3=Bogan|first3=Katrina L.|last4=Belenky|first4=Peter|last5=Wojcik|first5=Marzena|last6=Seidle|first6=Heather F.|last7=Nedyalkova|first7=Lyudmila|last8=Yang|first8=Tianle|last9=Sauve|first9=Anthony A.|last10=Park|first10=Hee-Won|last11=Brenner|first11=Charles|date=2007-10-02|title=Nicotinamide riboside kinase structures reveal new pathways to NAD+|journal=PLOS Biology|volume=5|issue=10|pages=e263|doi=10.1371/journal.pbio.0050263|issn=1545-7885|pmc=1994991|pmid=17914902}}</ref> elucidating the mechanism of synthesis of [[nicotinic acid adenine dinucleotide phosphate]],<ref>{{Cite journal|last1=Nam|first1=Tae-Sik|last2=Park|first2=Dae-Ryoung|last3=Rah|first3=So-Young|last4=Woo|first4=Tae-Gyu|last5=Chung|first5=Hun Taeg|last6=Brenner|first6=Charles|last7=Kim|first7=Uh-Hyun|title=Interleukin-8 drives CD38 to form NAADP from NADP+ and NAAD in the endolysosomes to mobilize Ca2+ and effect cell migration|journal=The FASEB Journal|year=2020|volume=34|issue=9|language=en|pages=12565–12576|doi=10.1096/fj.202001249R|pmid=32717131|issn=1530-6860|doi-access=free}}</ref> and discovering multiple conditions in which NAD metabolism is dysregulated in disease.<ref name=":2" /><ref name=":4">{{Cite journal|last1=Fons|first1=Nathan R.|last2=Sundaram|first2=Ranjini K.|last3=Breuer|first3=Gregory A.|last4=Peng|first4=Sen|last5=McLean|first5=Ryan L.|last6=Kalathil|first6=Aravind N.|last7=Schmidt|first7=Mark S.|last8=Carvalho|first8=Diana M.|last9=Mackay|first9=Alan|last10=Jones|first10=Chris|last11=Carcaboso|first11=Ángel M.|date=2019-08-22|title=PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma|journal=Nature Communications|language=en|volume=10|issue=1|page=3790|doi=10.1038/s41467-019-11732-6|pmid=31439867|pmc=6706443|bibcode=2019NatCo..10.3790F|issn=2041-1723}}</ref><ref name=":5" /><ref name=":1" /><ref name=":3" /><ref name=":6">{{Cite journal|last1=Covarrubias|first1=Anthony J.|last2=Kale|first2=Abhijit|last3=Perrone|first3=Rosalba|last4=Lopez-Dominguez|first4=Jose Alberto|last5=Pisco|first5=Angela Oliveira|last6=Kasler|first6=Herbert G.|last7=Schmidt|first7=Mark S.|last8=Heckenbach|first8=Indra|last9=Kwok|first9=Ryan|last10=Wiley|first10=Christopher D.|last11=Wong|first11=Hoi-Shan|date=November 2020|title=Senescent cells promote tissue NAD + decline during ageing via the activation of CD38 + macrophages|url= |journal=Nature Metabolism|language=en|volume=2|issue=11|pages=1265–1283|doi=10.1038/s42255-020-00305-3|pmid=33199924|issn=2522-5812|pmc=7908681}}</ref><ref name=":7">{{Cite journal|last1=Pirinen|first1=Eija|last2=Auranen|first2=Mari|last3=Khan|first3=Nahid A.|last4=Brilhante|first4=Virginia|last5=Urho|first5=Niina|last6=Pessia|first6=Alberto|last7=Hakkarainen|first7=Antti|last8=Kuula|first8=Juho|last9=Heinonen|first9=Ulla|last10=Schmidt|first10=Mark S.|last11=Haimilahti|first11=Kimmo|date=2020-06-02|title=Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy|url=http://www.sciencedirect.com/science/article/pii/S155041312030190X|journal=Cell Metabolism|language=en|volume=31|issue=6|pages=1078–1090.e5|doi=10.1016/j.cmet.2020.04.008|pmid=32386566|issn=1550-4131|hdl=10138/330502|s2cid=218585981|hdl-access=free}}</ref><ref name=":8">{{Cite journal|last1=Heer|first1=Collin D.|last2=Sanderson|first2=Daniel J.|last3=Voth|first3=Lynden S.|last4=Alhammad|first4=Yousef M. O.|last5=Schmidt|first5=Mark S.|last6=Trammell|first6=Samuel A. J.|last7=Perlman|first7=Stanley|last8=Cohen|first8=Michael S.|last9=Fehr|first9=Anthony R.|last10=Brenner|first10=Charles|date=2020-10-13|title=Coronavirus infection and PARP expression dysregulate the NAD Metabolome: an actionable component of innate immunity|url=https://www.jbc.org/content/295/52/17986.short|journal=Journal of Biological Chemistry|volume=295|issue=52|pages=17986–17996|doi=10.1074/jbc.RA120.015138|pmid=33051211|pmc=7834058|doi-access=free}}</ref>

Revision as of 14:44, 6 February 2023

Charles Brenner
Born(1961-10-30)October 30, 1961
NationalityAmerican
Alma materWesleyan University (B.A.)
Stanford University (Ph.D)
Brandeis University (Post-Doctoral)
Known forDiscovery and characterization of nicotinamide riboside as a vitamin
AwardsFellow of the American Association for the Advancement of Science
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
Notable studentsPeter A. Belenky, Samuel A.J. Trammell
Websitebrennerlab.net

Charles Brenner (born October 30, 1961) is the inaugural Alfred E Mann Family Foundation Chair of the Department of Diabetes & Cancer Metabolism at the Beckman Research Institute of the City of Hope National Medical Center. Brenner previously held the Roy J. Carver Chair in Biochemistry and was head of biochemistry at the University of Iowa.[1][2]

Brenner is a major contributor in the field of nicotinamide adenine dinucleotide (NAD) metabolism and has developed targeted, quantitative methods for NAD metabolomics.[3] Brenner discovered the eukaryotic nicotinamide riboside (NR) kinase pathway to NAD. He has characterized ways in which NAD is disrupted by diseases and metabolic stress.[2]

Education and career

Brenner graduated from Wesleyan University with a Bachelors degree in biology in 1983. After working for the biotechnology companies Chiron Corporation and DNAX Research Institute, Brenner attended graduate school at Stanford University School of Medicine. At Stanford he worked with Robert S. Fuller, receiving his Ph.D. in Cancer Biology in 1993. Brenner conducted post-doctoral research at Brandeis University with Gregory Petsko and Dagmar Ringe.[4][5]

Brenner then joined the faculty at Thomas Jefferson University, where he worked from 1996-2003, becoming Director of the Structural Biology & Bioinformatics Program in 2000. He moved to Dartmouth Medical School in 2003, serving as Associate Director for Basic Sciences at Norris Cotton Cancer Center (now named Dartmouth Cancer Center) from 2003-2009. In 2009 he joined the University of Iowa (UI) as Professor and Departmental Executive Officer (DEO) of Biochemistry. In 2010 he became the Roy J. Carver Chair of Biochemistry at UI, holding that position until 2020.[6][2][7]

In 2020, Brenner joined City of Hope National Medical Center in Duarte, California as the inaugural Alfred E Mann Family Foundation Chair in Diabetes and Cancer Metabolism. City of Hope created the position and the associated Department of Diabetes & Cancer Metabolism to focus on underlying metabolism and the intersection of metabolic disturbances with diseases such as cancer and diabetes.[2][1]

Research contributions

Brenner has made multiple contributions to molecular biology and biochemistry, beginning with purification and characterization of the Kex2 proprotein convertase at Stanford.[8][9] 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, the National Science Foundation and the Bill & Melinda Gates Foundation. Significant research projects include molecular dissection of the function of the FHIT tumor suppressor gene,[10][11] characterization and inhibition of DNA methylation,[12][13][14] and discovery of new steps in nicotinamide adenine dinucleotide metabolism.

Notably, the Brenner laboratory discovered that yeast uses nicotinamide riboside to make NAD+,[15][16][17] 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[18] and made fundamental contributions to NAD metabolism including discovery of nicotinic acid riboside-dependent NAD synthesis,[19] elucidating the mechanism of synthesis of nicotinic acid adenine dinucleotide phosphate,[20] and discovering multiple conditions in which NAD metabolism is dysregulated in disease.[21][22][23][24][25][26][27][28]

Brenner is also active in translating NR technologies to treat and prevent human conditions that disturb the NAD system including cancer,[22] diabetic and chemotherapeutic peripheral neuropathy,[23][24] heart failure,[21] central brain injury,[25] inflammation,[26] mitochondrial myopathy[27] and coronavirus infection.[28] Brenner's work included the first human trial of NR, which demonstrated safe oral availability as an NAD+ precursor.[29] Though Brenner was the first to show that NR increases SIR2 activity and can extend yeast lifespan,[17] his work has not emphasized sirtuins or nonspecific anti-aging claims and instead emphasizes how NR repairs metabolic stresses that dysregulate NAD+[21][25] and NADPH.[24]

Brenner 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.[30][31][32]

Brenner is an author of more than 200 peer-reviewed publications.[33] He was the senior editor of the 2004 book, Oncogenomics: Molecular Approaches to Cancer.[34]

Brenner is both cautious and critical of research that promotes claims of anti-aging and longevity.[35][36][37] After writing a favorable review of Steven Austad's book Methuselah's Zoo,[38] he reviewed Lifespan: Why We Age – and Why We Don't Have To by David A. Sinclair, summarizing it as "an influential source of misinformation on longevity, featuring counterfactual claims about longevity genes being conserved between yeast and humans, the existence of supposed activators of these genes, and claimed successful age reversal in mice based on partial reprogramming."[39] Brenner published a major review of sirtuins in 2022 entitled "Sirtuins are not conserved longevity genes".[40]

Educational contributions

External videos
video icon “Charles Brenner: ASBMB Award for Exemplary Contributions to Education Lecture”, May 25, 2016.

In 2012, Brenner and Dagmar Ringe developed pre-medical curriculum recommendations that would be consistent with a revised Medical College Admission Test (MCAT), following a request from the President of the American Society for Biochemistry and Molecular Biology, Suzanne Pfeffer.[41][42] The 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. Brenner's contribution to this area was recognized by the 2016 ASBMB Award for Exemplary Contributions to Education.[43]

Industrial collaborations

Brenner is a former member of the Scientific Advisory Board of Sirtris Pharmaceuticals.[44] He is the founder of NRomics[45] 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.[4][46]

Awards

Selected publications

References

  1. ^ a b "Leading Biochemist Charles Brenner, PhD, Joins City of Hope as Chair of First Department Focused on Diabetes and Cancer Metabolism". OncLive. MJH Life Sciences. Aug 27, 2020. Retrieved 3 February 2023.
  2. ^ a b c d "Brenner stepping down as chair of Department of Biochemistry | Department of Biochemistry and Molecular Biology". University of Iowa. July 8, 2020. Retrieved 2 February 2023.
  3. ^ "Awards for Regev and Gierasch; new job for Brenner". ASBMB Today. July 20, 2020.
  4. ^ a b "ChromaDex To Host Key Opinion Leader Webinar on the Transforming Benefits of Nicotinamide Riboside (NR)". BusinessWire. July 7, 2022. Retrieved 3 February 2023.
  5. ^ "Vital Signs: Investigator Insight". Dartmouth Medicine Magazine. Vol. 28, no. 4. 2004. Retrieved 2 February 2023.
  6. ^ "Brenner Named Head of Biochemistry at UI Carver College of Medicine". News-releases.uiowa.edu. May 5, 2009. Archived from the original on July 20, 2011. Retrieved December 9, 2010.
  7. ^ "CV". Brenner Lab. Retrieved 3 February 2023.
  8. ^ Nakayama, Kazuhisa (1 November 1997). "Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins". Biochemical Journal. 327 (3): 625–635. doi:10.1042/bj3270625. Retrieved 6 February 2023.
  9. ^ Sreenivas, Suma; Krishnaiah, Sateesh M.; Govindappa, Nagaraja; Basavaraju, Yogesh; Kanojia, Komal; Mallikarjun, Niveditha; Natarajan, Jayaprakash; Chatterjee, Amarnath; Sastry, Kedarnath N. (January 2015). "Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris". Applied Microbiology and Biotechnology. 99 (1): 327–336. doi:10.1007/s00253-014-6052-5. {{cite journal}}: |access-date= requires |url= (help)
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ James Theoga Raj, Christol; Lin, Su-Ju (October 2019). "Cross-talk in NAD+ metabolism: insights from Saccharomyces cerevisiae". Current Genetics. 65 (5): 1113–1119. doi:10.1007/s00294-019-00972-0. PMID 30993413.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  20. ^ 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. 34 (9): 12565–12576. doi:10.1096/fj.202001249R. ISSN 1530-6860. PMID 32717131.
  21. ^ 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.
  22. ^ 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.
  23. ^ a b New Vitamin May Relieve a Painful Problem Archived 2013-08-19 at the Wayback Machine Focus April 20, 2008
  24. ^ 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.
  25. ^ 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.
  26. ^ 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. PMC 7908681. PMID 33199924.
  27. ^ 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. hdl:10138/330502. ISSN 1550-4131. PMID 32386566. S2CID 218585981.
  28. ^ 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. PMC 7834058. PMID 33051211.
  29. ^ 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.
  30. ^ 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.
  31. ^ Cell Press, Combating Postpartum Metabolic Stress/Cell Reports, Jan. 22, 2019 (Vol. 22, Issue 4), archived from the original on 2021-12-21, retrieved 2019-01-26
  32. ^ "Supplement makes (mouse) moms' milk better; pups benefit for life". medicalxpress.com. Retrieved 2019-01-26..
  33. ^ "Charles Brenner". scholar.google.com. Retrieved 3 February 2023.
  34. ^ Brenner, Charles; Duggan, David, eds. (2004). Oncogenomics : molecular approaches to cancer. Hoboken, N.J.: Wiley-Liss. ISBN 0-471-22592-4.
  35. ^ Ritchie, Stuart (24 January 2023). "Why you shouldn't get too excited at claims scientists have reversed ageing... yet". inews.co.uk. Retrieved 3 February 2023.
  36. ^ Colbert, Chris (13 May 2022). "Unpacking Longevity: The Myths of Anti-Aging". Private Medical. Retrieved 2 February 2023.
  37. ^ Garth, Eleanor (2 November 2022). "Charles Brenner: longevity is not a simple engineering problem". Longevity.Technology - Latest News, Opinions, Analysis and Research. Retrieved 3 February 2023.
  38. ^ Brenner, Charles (2022-08-12). "Longevity lessons Methuselah's Zoo: What Nature Can Teach Us About Living Longer, Healthier Lives Steven N. Austad MIT Press, 2022. 320 pp". Science. 377 (6607): 718. doi:10.1126/science.add9130. ISSN 0036-8075. PMID 35951694. S2CID 251516708.
  39. ^ Brenner, Charles (2023-01-01). "A science-based review of the world's best-selling book on aging". Archives of Gerontology and Geriatrics. 104: 104825. doi:10.1016/j.archger.2022.104825. ISSN 0167-4943. PMC 9669175. PMID 36183524.
  40. ^ Brenner, Charles (2022-09-22). "Sirtuins are not conserved longevity genes". Life Metabolism: loac025. doi:10.1093/lifemeta/loac025. ISSN 2755-0230.
  41. ^ Brenner, Charles; Ringe, Dagmar (2012). "Response to the New MCAT: ASBMB Premedical Curriculum Recommendations" (PDF). ASBMB Today. No. March. pp. 12–14.
  42. ^ "Chapter 1: Introduction and Overview". Undergraduate Chemistry Education: A Workshop Summary. Washington, D.C.: National Academies Press. 24 March 2014. p. 1. ISBN 978-0-309-29589-5.
  43. ^ a b Sengupta, Samarpita (March 1, 2016). "Brenner recognized for devotion to 'cutting-edge education' and serving the biomedical community". ASBMB Today. Retrieved 2 February 2023.
  44. ^ "Sirtris Pharmaceuticals, Inc. offering of common stock, Filed Pursuant to Rule 424(b)(4) Registration No.: 333-140979". www.sec.gov. May 22, 2007. Retrieved 2 February 2023.
  45. ^ "NROMICS LLC". opencorporates.com. Retrieved 3 February 2023.
  46. ^ "Charles Brenner Ph.D." Bloomberg. Retrieved 1 August 2018.
  47. ^ "ChromaDex Chief Scientific Advisor Dr. Charles Brenner Receives 2020 National Scientific Achievement Award from the American Society for Nutrition". BusinessWire. May 21, 2020.
  48. ^ "AAAS Members Elected as Fellows". American Association for the Advancement of Science (AAAS). 30 November 2012. Retrieved 2 February 2023.
  49. ^ "William E. M. Lands Lectureship | Biological Chemistry | Michigan Medicine". Biological Chemistry. 22 March 2018. Retrieved 2 February 2023.
  50. ^ a b "Curriculum Vitae | Charles Brenner Laboratory". University of Iowa. Retrieved 2 February 2023.
  51. ^ "Charles Brenner". Arnold and Mabel Beckman Foundation. Archived from the original on 2 August 2018. Retrieved 1 August 2018.

External links

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