We are a research group in the Dartmouth Medical School Departments
of Genetics, Biochemistry and the Norris Cotton Cancer Center, Dartmouth's NCI-designated comprehensive
cancer center. The Brenner laboratory has three research interests.
First, we study the function of histidine triad hydrolases including Hint, Aprataxin,
and Fhit,
their homologs, and their signaling partners. This work has led us into
fascinating areas of biology including sex determination in birds, ataxia-oculomotor apraxia, vitamin C synthesis, and a frequently
inactivated proapoptotic tumor suppressor pathway. Going forward, we are focused on the gene expression consequences of loss of Fhit expression in human bronchial epithelial cells.
Second, we are interested in unsolved problems of NAD+ metabolism, especially as related to aging. We recently described two pathways to NAD+ in fungi and humans that originate from nicotinamide riboside, and we are engaged in discovery and validation of additional NAD+ metabolic genes as well. These pathways are of interest because they are regulated by the availability of vitamins and calories. Some of the pathways are induced in response to nerve damage. Thus, though our work is fundamentally based, there is potential for nutritional or therapeutic interventions that could improve human health.
Finally, we are interested in a pathway for translational and post-translational control of the cell cycle at the G1-S and G2-M transitions that we call the Cdc123/D123-Chfr-eIF2gamma axis of cell division control. In this project, we use yeast genetics, enzymology, mass spectrometry and cell biology to identify the targets of RING E3 ubiquiting ligases that are homologous to the Chfr tumor suppressor protein and to identify the ubiquitin conjugating enzymes and other accessory proteins involved in Chf protein target regulation. This interdisciplinary approach has allowed us to establish a dual requirement for Ubc4 and for Ubc13/Mms2 in the cell cycle-delaying activity of yeast Chf2.
For more information on these topics,
please download our publications. Please also feel free to contact Brenner lab personnel.
Dr. Brenner's
training included yeast
genetics with Kunihiro
Matsumoto, yeast molecular biology with Tony Brake, enzyme purification and kinetics with Bob Fuller, and X-ray crystallography
with Greg Petsko
and Dagmar Ringe.
The 2004 book, Oncogenomics: Molecular Approaches to Cancer, is available from Wiley and Amazon. Please read Dr. Franco Cavalli's review of Oncogenomics in the New England Journal of Medicine.
Prospective graduate students should apply through the Dartmouth Ph.D. program in Molecular and Cellular
Biology. Prospective undergraduates and post-doctoral fellows may be in touch directly. Prospective M.D./Ph.D. trainees may conduct graduate research in MCB or
Computational Biology.
Dr. Brenner serves as associate director for basic sciences of the Norris Cotton Cancer Center and scientific director of the Comprehensive Thoracic Oncology Program. Outside of the cancer center, he participates in the biophysics and fungal cell biology interest groups and in the Neurosciences
Center at Dartmouth.
Course websites are available for Genetics 144, Oncogenomics and for the Yeast Genetics Lecture that used to be part of the MCB Core Course.
Archival lecture notes are available for courses developed at Jefferson:
The Yeast Transformation Tutorial for BI 532, "Experimental Principles in Molecular Biology"
The Difference Patterson Tutorial for PR 613, "Structural Biology I"
The Yeast Genetics Lectures for GE 611, "Introduction to
Molecular Genetics"
Those interested in obtaining the fluorescent and fluorigenic nucleotide analogs, ApppBODIPY and GpppBODIPY, described in Draganescu et al, may obtain reagents from Invitrogen.
Funded positions are usually available so please be in touch.
Charles
Brenner, Ph.D.
Professor of Genetics and of Biochemistry
Norris Cotton Cancer Center
Dartmouth Medical School
Rubin 733--HB7937
Lebanon, NH 03756
parcels:
Dr. Charles Brenner
Dartmouth-Hitchcock Medical Center
1 Medical Center Drive
Rubin Building, room 733
Lebanon, NH 03756
office 603-653-9922
fax 603-653-9923
lab 603-653-9925,6
Email: charles.brenner AT dartmouth.edu