Brett A. Kaufman, PhD
Brett Kaufman, PhD
Associate Professor of Medicine,
Education and Training
Indiana University, 1995
PhD (Cell and Molecular Biology)
University of Texas Southwestern Medical Center at Dallas, 2003
My long-standing research interest is to understand the contribution of mtDNA metabolism to disease progression. For 20 years I have been uncovering the fundamental processes that underlie mitochondrial respiratory deficiency with a focus on mtDNA stability and copy number control – processes essential for respiratory function and viability. My major research goals are 1) to define the biochemical events responsible for the maintenance of mtDNA content, 2) to understand how distinct pathways influence mtDNA maintenance, and 3) to understand mechanisms of mtDNA damage and resistance to damage in the context of disease. These goals are manifest in the following research projects:
Mechanisms of mtDNA integrity and expression. We are extending our understanding of how helicases interact with specific mtDNA sequences and structures to ensure genome stability and expression. We are employing the latest genome-wide high density sequencing approaches, super-resolution microscopy, and genome editing approaches to understand how deletions are formed and development respiratory dysfunction.
TFAM function in the genome stability. We are working to understand the role of the mitochondrial transcription and packaging factor TFAM in protecting the mitochondrial genome, controlling accessibility, and establishing mtDNA copy number. This work is being further extended to understand the process of regulating TFAM to these ends. Human, animal, and cell-based models are being are being used to identify regulatory networks that might be leveraged to improve genome stability and expression.
The role of mtDNA genome stability in cardiovascular disease. We are using human patient samples and animal models of cardiopulmonary diseases to understand the role of mitochondrial genome damage and reactive oxygen species in the susceptibility or progression of disease.
We are always looking for hard-working scientists to join our team!
Kaufman B.A.*, Newman S.M*, Hallberg R.L., Slaughter C.A., Perlman P.S., and Butow R.A. (2000) In organello formaldehyde crosslinking of proteins to mtDNA: Identification of bifunctional proteins. Proceedings of the National Academy of Sciences, U.S.A. 97: 7772-7777. PMC16620. *these authors contributed equally to this work.
Kaufman B.A., Newman S.M., Perlman P.S., and Butow R.A. (2002) Crosslinking of proteins to mtDNA in Methods in Molecular Biology, (Copeland, W.C., ed.), 197: 377-389. Humana Press, Totowa, U.S.A.
Kaufman B.A., Kolesar J.E., Perlman P.S., and Butow R.A. (2003) A function for the mitochondrial chaperonin Hsp60 in the structure and transmission of mitochondrial DNA nucleoids in Saccharomyces cerevisiae. Journal of Cell Biology 163: 457-461. PMC2173642
Leary S.C., Kaufman B.A., Pellecchia G., Guercin G.H., Mattman A., Jaksch M., and Shoubridge E.A. (2004) Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase. Human Molecular Genetics 13: 1839-1848.
Chen X.J., Wang X., Kaufman B.A., and Butow R.A. (2005) Aconitase couples metabolic regulation to mitochondrial DNA maintenance. Science 307: 714-717.
Leary S.C., Cobine P.A., Kaufman B.A., Guercin G.H., Mattman A., Palaty J., Lockitch G., Winge D.R., Rustin P., Horvath R., and Shoubridge, E.A. (2007) The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis. Cell Metabolism 5: 9-20.
Kaufman B.A.*, Durisic N.*, Mativetsky J.M., Costantino S., Hancock M.A., Grutter P., and Shoubridge E.A. (2008) The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures. Molecular Biology of the Cell 18: 3225-3236. *these authors contributed equally to this work. PMC1951767.
Weraarpachai W., Antonicka H., Sasarman F., Seeger J., Schrank B., Kolesar J.E., Lochmüller H., Chevrette M., Kaufman B.A., Horvath R., Shoubridge E.A. (2009) Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome. Nature Genetics 41: 833-7.
Campbell C.T., Kolesar J.E., and Kaufman B.A. (2012) Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochimica et Biophysica Acta 1819: 921-929.
Mallilankaraman K., Cárdenas C., Doonan P., Chandramoorthy H.C., Irrinki K.M., Golenár T., Csordás G., Madireddi P., Yang J., Müller M., Miller R., Kolesar J.E., Molgó J., Kaufman B.A., Hajnóczky G., Foskett J.K., Madesh M. (2012) MCUR1 is an Essential Component of Mitochondrial Ca2+ Uptake that Regulates Cellular Metabolism. Nature Cell Biology 24: 1336-1343. PMC3511605.
Soubannier V., Rippstein P., Kaufman B.A., Shoubridge E.A., McBride H.M. (2012) Reconstitution of mitochondria derived vesicle formation demonstrates selective enrichment of oxidized cargo. PLoS ONE 7: e52830. PMC3530470.
Kolesar J.E, Wang C.Y., Taguchi, Y.V., Chou S.-H., Kaufman, B.A. (2013) Two-dimensional intact mitochondrial DNA agarose electrophoresis reveals the structural complexity of the mammalian mitochondrial genome. Nucleic Acids Research 41(4): e58. PMC3575812.
Soleimanpour S.A., Gupta A., Bakay M., Ferrari A.M., Groff D.N., Fadista J., Spruce L.A., Kusher J.A., Groop L., Seeholzer S.H., Kaufman B.A., Hakonarson H., Stoffers D.A. (2014) The diabetes susceptibility gene Clec16a regulates mitophagy. Cell 157: 1577-90. PMCID: PMC4184276.
Dong D., Pereira F., Barrett S.P., Kolesar J.E., Yatsunyk L.A., Cao K., Damas J., Johnson, F.B., and Kaufman B.A. (2014) Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints. BMC Genomics 15: 677. PMC4153896.
Kolesar J.E., Safdar A., Abadi A, MacNeil L.G., Crane J.D., Tarnopolsky M.A., and Kaufman B.A. (2014) Mitochondrial oxidative damage accompanies muscle atrophy in mtDNA mutator mice. Free Radicals Biology & Medicine 75: 241-51.
Kaufman B.A., Liu C., Soleimanpour S. (2015) Mitochondrial regulation of beta cell function: maintaining the momentum for insulin release. Molecular Aspects of Medicine 42: 91-104. PMC4404204.
Shanmughapriya S., Rajan S,. Hoffman N.E., Zhang X., Guo S., Kolesar J.E., Hines K.J., Ragheb J., Jog N.R., Caricchio R., Baba Y., Zhou Y., Kaufman B.A., Cheung J.Y., Kurosaki T., Gill D.L., and Madesh M. (2015) Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene MCU. Sci Signaling 8(366): ra23.
Soleimanpour S.A., Ferrari A.M., Raum J.C., Groff D.N., Yang J., Kaufman B.A., Stoffers D.A. (2015) Diabetes susceptibility genes Pdx1 and Clec16a function in a pathway regulating mitophagy in β-cells. Diabetes. [Epub ahead of print] PMID: 26085571.