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Department of Biochemistry

Professor and Head of Biochemistry

Carver College of Medicine
University of Iowa
51 Newton Rd
4-403 BSB
Iowa City, IA 52242
Jan Shields: 319-335-7933
Office: 319-335-7934
Lab: 319-384-4099
charles-brenner@uiowa.edu

Research Interests

Tumor suppressor genes are a class of genes inactivated in carcinogenesis. The best understood tumor suppressors are positive regulators of programmed cell death or negative regulators of cell proliferation. However, it is becoming clear that tumor suppressor genes have a wide array of functions in normal cells, such that their losses in early or late stages of carcinogenesis can contribute to malignant phenotypes. Our research group conducts interdisciplinary research into the function of the human FHIT gene, which is frequently lost in premalignant carcinogen-exposed epithelia and into the function of yeast homologs of the human CHFR gene, which is inactivated later in the development of epithelial malignancies.

Our latest research indicates that FHIT inactivation from bronchial epithelial cells induces a series of gene expression changes that may underlie early steps in carcinogenesis. We are conducting experiments to dissect the mechanism by which FHIT losses induce these gene expression changes and are using genomic methods to fully understand their consequences.

Work on Chf1 and Chf2, the yeast homologs of Chfr, indicates that these RING domain-containing E3 ubiquitin ligases utilize two different ubiquitin conjugating enzymes to regulate cell cycle transitions early and late in the cell cycle. Our research on these enzymes combines protein mass spectrometry with enzymology, genetics and cell biology to define the targets, pathways and consequences of Chf1 and Chf2 function in yeast cells.

Several years ago, we developed an interest in the metabolism of nicotinamide adenine dinucleotide (NAD). This molecule serves as a coenzyme for hydride transfer reactions common in intermediary metabolism and as a substrate for NAD-dependent signaling enzymes, such as sirtuins and poly(ADPribose) polymerases. Though it had been thought that all of the steps in NAD biosynthesis were known, our group discovered the genes, enzymes and transporters involved in the utilization of nicotinamide riboside and nicotinic acid riboside. Our current work is aimed at dissecting the regulation of NAD metabolism as a function of changing nutritional inputs in yeast cells and in mammals.

Recent Publications

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). Download pdf reprint

G.L. Loring, K.C. Christensen, S.A. Gerber & C. Brenner, "Yeast Chfr Homologs Retard Cell Cycle at G1 and G2/M via Ubc4 and Ubc13/Mms2-Dependent Ubiquitination," Cell Cycle, v. 7, pp. 95-105 (2008). Download pdf reprint

Pubmed all of Dr. Brenner's publications.

Affiliations

Biochemistry Department
Molecular & Cellular Biology Ph.D. Program
Genetics Ph.D. Program
Holden Comprehensive Cancer Center
Center for Biocatalysis and Bioprocessing

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