Brett A. Kaufman, Ph.D.

faculty photo
Assistant Professor of Biochemistry
Department: Biochemistry
Graduate Group Affiliations

Contact information
School of Veterinary Medicine
Laboratories of Biochemistry
3800 Spruce Street
220E OVH
Philadelphia, PA 19104-6046
Office: 215.746.4135
Fax: 215.573.5187
Education:
BS (Biochemistry)
Indiana University, 1995.
Ph.D. (Cell and Molecular Biology)
University of Texas Southwestern Medical Center at Dallas, 2003.
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Description of Research Expertise

Our primary research focus is on the regulation of mitochondrial chromatin, and its effect on genome segregation, compaction, and expression. The coordination of these processes is essential for the maintenance and transmission of mitochondrial respiratory function. By analogy to the nuclear genome, whose regulated compaction/decompaction is an essential aspect of replication, transcription and transmission, regulated compaction of the mitochondrial genome is likely to be a key aspect of mitochondrial biology. In vivo, mtDNAs are organized into nucleoids, which are small, suborganellar protein-DNA complexes that contain a few copies of the genome. These structures are present as several hundred distinct foci, depending on cell type. The core of our research lies in determining how the nucleoid is formed and regulated, and how that regulation affects developmental and physiological aspects of mitochondrial function such as tissue-specific segregation of mutant mtDNA. This work has implications in diabetes, aging, heart disease, and mtDNA-borne birth defects.

We have several thrusts in the lab as of now: 1) post-translational regulation of mtDNA compaction 2) genes involved in the somatic segregation of mtDNA alleles, and 3) identification and characterization of protein-mtDNA complexes.

Selected Publications

Weraarpachai W, Antonicka H, Sasarman F, Seeger J, Schrank B, Kolesar JE, Lochmüller H, Chevrette M, Kaufman BA, Horvath R, Shoubridge EA.: Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome. Nature Genetics 41(7): 833-7, Jul 2009.

Kaufman, Brett A. Durisic, Nela. Mativetsky, Jeffrey M. Costantino, Santiago. Hancock, Mark A. Grutter, Peter. Shoubridge, Eric A.: The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures. Molecular Biology of the Cell 18(9): 3225-36, Sep 2007.

Leary, Scot C. Cobine, Paul A. Kaufman, Brett A. Guercin, Guy-Hellen. Mattman, Andre. Palaty, Jan. Lockitch, Gillian. Winge, Dennis R. Rustin, Pierre. Horvath, Rita. Shoubridge, Eric A.: The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis.[erratum appears in Cell Metab. 2007 May;5(5):403]. Cell Metabolism 5(1): 9-20, Jan 2007.

Chen, Xin Jie. Wang, Xiaowen. Kaufman, Brett A. Butow, Ronald A.: Aconitase couples metabolic regulation to mitochondrial DNA maintenance. Science 307(5710): 714-7, Feb 4 2005.

Leary, Scot C. Kaufman, Brett A. Pellecchia, Giovanna. Guercin, Guy-Hellen. Mattman, Andre. Jaksch, Michaela. Shoubridge, Eric A.: Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase. Human Molecular Genetics 13(17): 1839-48, Sep 1 2004.

Kaufman, Brett A. Kolesar, Jill E. Perlman, Philip S. Butow, Ronald A.: A function for the mitochondrial chaperonin Hsp60 in the structure and transmission of mitochondrial DNA nucleoids in Saccharomyces cerevisiae. Journal of Cell Biology 163(3): 457-61, Nov 10 2003.

Kaufman, Brett A. Newman, Scott M. Perlman, Philip S. Butow, Ronald A.: Crosslinking of proteins to mtDNA. Methods in Molecular Biology 197: 377-89, 2002.

Kaufman, B A. Newman, S M. Hallberg, R L. Slaughter, C A. Perlman, P S. Butow, R A.: In organello formaldehyde crosslinking of proteins to mtDNA: identification of bifunctional proteins. Proceedings of the National Academy of Sciences of the United States of America 97(14): 7772-7, Jul 5 2000.

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Last updated: 07/10/2009
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