Charles Brenner, Ph.D.
Professor of Genetics and of Biochemistry
Associate Director, Basic Sciences
Scientific Director, Comprehensive Thoracic Oncology Program
| Contact Information |
| Phone: 603-653-9922 |
| Fax: 603-653-9923 |
| Lab phone: 603-653-9925/9926 |
| Email Address: charles DOT brenner AT dartmouth DOT edu |
| Website: http://www.dartmouth.edu/~brenner/cv.html |
| Laboratory Website : http://www.dartmouth.edu/~brenner/ |
Postal Address |
| Dr. Charles Brenner |
| Dartmouth Medical School |
| Rubin 733--HB7937 |
| Lebanon, NH 03756 |
Address for Parcels:
One Medical Center Drive
|
Education |
| Wesleyan University, BA (1979-1983) |
| Stanford University School of Medicine, Ph.D. (1988-1993) |
| Brandeis University, Post-doctoral (1993-1996) |
Program Membership |
| Cancer Mechanisms Research Program |
Department Membership |
| Genetics |
| Biochemistry |
Graduate Training Program Affiliation |
| Molecular and Cellular Biology |
Biography |
| Dr. Brenner began his career at Chiron (1983-1985) and DNAX (1986-1988) in yeast molecular biology and yeast genetics before working on the enzymology of the Kex2 prohormone processing enzyme with Robert Fuller in the Biochemistry Department at Stanford. After receiving his Ph.D. in Cancer Biology, he moved to Brandeis in 1993, where he was a Leukemia Society Fellow with Gregory Petsko and Dagmar Ringe, studying X-ray crystallography and discovering that histidine triad enzymes are a superfamily of nucleotide hydrolases and transferases. In 1996, he took a position as assistant professor in Philadelphia's Kimmel Cancer Center and served as associate professor and director of the KCC's Program in Structural Biology and Bioinformatics from 2000 until his research group moved to Dartmouth in 2003. He was promoted to Professor of Genetics and of Biochemistry in 2007. Dr. Brenner is a founding member of the editorial board of Genome Biology and the co-editor of Oncogenomics: Molecular Approaches to Cancer. |
Selected Recent Publications |
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Trapazzo, F., Krakowiak, A., Cesari, R., Arkles, J., Yenamuri, S., Ishii, H., Vecchione, A., Kuroki, T., Bieganowski, P., Pace, H.C., Huebner, K., Croce, C.M. and Brenner, C., "Designed FHIT Alleles Establish that Fhit-Induced Apoptosis in Cancer Cells is Limited by Substrate-Binding," Proc. Natl. Acad. Sci., v. 100, pp. 1592-1597, 2003.
Brenner, C. and Duggan D., Oncogenomics: Molecular Approaches to Cancer, John Wiley & Sons, New York, 2004. 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). P. Bieganowski, K. Shilinski, P.N. Tsichlis & C. Brenner, "Cdc123 and Checkpoint Forkhead Associated With RING Proteins Control the Cell Cycle By Controlling eIF2gamma Abundance, " J. Biol. Chem., v. 279, pp. 44656-44666 (2004). H.F. Seidle, P. Bieganowski & C. Brenner, "Disease-Associated MutationsInactivate AMP-Lysine Hydrolase Activity of Aprataxin," J. Biol. Chem., v.280, pp. 20927-20931 (2005). P. Belenky, K.L. Bogan & C. Brenner, "NAD+ Metabolism in Health and Disease," Trends in Biochemical Sciences, v. 32, pp. 12-19 (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, e263 (2007). Pubmed all of Dr. Brenner's publications. |
Research / Lab Interests |
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The Brenner group is interested in fundamental problems in cell cycle and
metabolism, especially as related to carcinogenesis and cancer treatment.
The FHIT gene is inactivated early in carcinogenesis of lung and other epithelial exposed tissue. Using the Microarray and Bioinformatics shared resources, the Brenner group has defined the earliest gene expression consequences of loss of Fhit protein from bronchial epithelia. In collaboration with Wendy Wells, Vincent Memoli and Angeline Andrew, they are examining the prevalence of these correlated alterations in human lung cancer and they are dissecting the mechanisms by which Fhit inactivation derepresses a set of cancer genes. The CHFR gene is also frequently lost in the development of epithelial carcinomas. Encoding a RING E3 ubiquitin ligase, the targets of Chfr remain controversial and the mechanisms by which Chfr functions remain incompletely understood. The Brenner group cloned and characterized Chf1 and Chf2, the two yeast homologs of Chfr and has determined the E2 ubiquitin conjugating enzymes required for two distinguishable cell cycle effects of Chf2. In collaboration with Scott Gerber and with the use of new NCCC instrumentation, the Brenner group defined site-specific and linkage specific ubiquitination activities of Chf1 and Chf2 in a purified, reconstituted system with genetically validated components. Gerber and Brenner plan to use high resolution mass spectrometry to identify targets of Chf proteins and Chfr. With seed funding from NCCC developmental funds, the Brenner group discovered two new metabolic pathways by which eukaryotic cells make NAD+ from nicotinamide riboside (NR), a natural product found in milk. Because increased neuronal NAD+ synthesis has been shown to protect against chemotherapy-induced neurodegeneration, Brenner is working with Alexandre Pletnev and Lionel Lewis to test NR in models of chemotherapy-induced peripheral neuropathy. |
| The Brenner group rides in the Friends of Norris Cotton Cancer Center's Annual Prouty Century Bike Ride & Challenge Walk. |
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| 2007-2011 NIH R01 GM081665, "Quantitative Analysis of RING E3 Ubiquitin Ligases" |
| 1997-2008 NIH R01 CA075954, "Functional and Structural Analysis of HIT Proteins" |
| 2007 William E.M. Lands Lecturer in Nutritional Biochemistry, University of Michigan |
| 1998-2000 Basil O'Connor Scholar of the March of Dimes Birth Defects Foundation |
| 1998-2001 Beckman Young Investigator of the Arnold and Mabel Beckman Foundation |
| 1998-2001 Burroughs Wellcome Foundation New Investigator in the Basic Pharmacological Sciences |
