Douglas C. Wallace, PhD
Locations: Main Building
About Douglas C. Wallace, PhD
More than 35 years ago, Dr. Wallace and his colleagues founded the field of human mitochondrial genetics. The mitochondria are the cellular power plants, organelles that generate most of the cell’s energy. The mitochondria also contain their own DNA, the mitochondrial DNA (mtDNA), which encodes the wiring diagram for the cell’s power plants. Dr. Wallace showed that the mtDNA is inherited exclusively from the mother and that genetic alterations in the mtDNA can result is a wide range of metabolic and degenerative diseases as well as being important in cancer and aging.
One of his seminal contributions has been to use mtDNA variation to reconstruct the origin and ancient migrations of women. These studies revealed that humans arose in Africa approximately 200,000 years ago, that women left Africa about 65,000 years ago to colonize Eurasia, and from Siberia, they crossed the Bering land bridge to populate the Americas. Studies on the paternally-inherited Y chromosome showed that men went along too.
Titles
Director, Center for Mitochondrial and Epigenomic Medicine
Research Interests
The role of mitochondrial energy in human health and disease
Education & training
Undergraduate Degree
BS, Genetics, Developmental Biology, Cornell University, Ithaca, NY
MPhil, Microbiology and Human Genetics, Yale University
Graduate Degree
PhD, Microbiology and Human Genetics, Yale University, New Haven, Ct.
Fellowship
NIH Postdoctoral Fellowship, Department of Human Genetics, Yale University
Publications
Publications
2010
Zaragoza MV, Brandon MC, Diegoli M, Arbustini E, Wallace DC. Mitochondrial cardiomyopathies: how to identify candidate pathogenic mutations by mitochondrial DNA sequencing, MITOMASTER and phylogeny. Eur J Hum Genet. 2010 Oct 27. [Epub ahead of print]
Badadani M, Nalbandian A, Watts GD, Vesa J, Kitazawa M, Su H, Tanaja J, Dec E, Wallace DC, Mukherjee J, Caiozzo V, Warman M, Kimonis VE. VCP associated inclusion body myopathy and paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease. PLoS One. 2010 Oct 5;5(10). pii: e13183.
Wallace DC. Bioenergetics and the epigenome: interface between the environment and genes in common diseases. Dev Disabil Res Rev. 2010 Jun;16(2):114-9.
Poole JC, Procaccio V, Brandon MC, Merrick G, Wallace DC. Multiplex analysis of mitochondrial DNA pathogenic and polymorphic sequence variants. Biol Chem. 2010 Oct;391(10):1115-30.
Wallace DC. Mitochondrial DNA mutations in disease and aging. Environ Mol Mutagen. 2010 Jun;51(5):440-50. Review.
Lakatos A, Derbeneva O, Younes D, Keator D, Bakken T, Lvova M, Brandon M, Guffanti G, Reglodi D, Saykin A, Weiner M, Macciardi F, Schork N, Wallace DC, Potkin SG; Alzheimer's Disease Neuroimaging Initiative. Association between mitochondrial DNA variations and Alzheimer's disease in the ADNI cohort. Neurobiol Aging. 2010 Aug;31(8):1355-63. Epub 2010 Jun 11.
Coskun PE, Wyrembak J, Derbereva O, Melkonian G, Doran E, Lott IT, Head E, Cotman CW, Wallace DC. Systemic mitochondrial dysfunction and the etiology of Alzheimer's disease and down syndrome dementia. J Alzheimers Dis. 2010;20 Suppl 2:S293-310.
Wallace DC. Colloquium paper: bioenergetics, the origins of complexity, and the ascent of man. Proc Natl Acad Sci USA. 2010 May 11;107 Suppl 2:8947-53. Epub 2010 May 5.
Lim TS, Dávila A, Wallace DC, Burke P. Assessment of mitochondrial membrane potential using an on-chip microelectrode in a microfluidic device. Lab Chip. 2010 Jul 7;10(13):1683-8. Epub 2010 Apr 12.
Kenney MC, Atilano SR, Boyer D, Chwa M, Chak G, Chinichian S, Coskun P, Wallace DC, Nesburn AB, Udar NS. Characterization of retinal and blood mitochondrial DNA from age-related macular degeneration patients. Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4289-97. Epub 2010 Mar 31.
Hendrickson SL, Jabs DA, Van Natta M, Lewis RA, Wallace DC, O'Brien SJ. Mitochondrial haplogroups are associated with risk of neuroretinal disorder in HIV-positive patients. J Acquir Immune Defic Syndr. 2010 Apr 1;53(4):451-5.
Wallace DC, Fan W, Procaccio V. Mitochondrial energetics and therapeutics. Annu Rev Pathol. 2010;5:297-348. Review.
2009
Wallace DC. Mitochondria, bioenergetics, and the epigenome in eukaryotic and human evolution. Cold Spring Harb Symp Quant Biol. 2009;74:383-93. Epub 2009 Dec 2. Review.
Vesa J, Su H, Watts GD, Krause S, Walter MC, Martin B, Smith C, Wallace DC, Kimonis VE. Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts. Neuromuscul Disord. 2009 Nov;19(11):766-72. Epub 2009 Oct 13. Free PMC Article.
Wallace DC, Fan W. Energetics, epigenetics, mitochondrial genetics. Mitochondrion. 2010 Jan;10(1):12-31. Epub 2009 Sep 29. Review.
Wallace DC, Fan W. The pathophysiology of mitochondrial disease as modeled in the mouse. Genes Dev. 2009 Aug 1;23(15):1714-36. Review. Free PMC Article.
Su H, Fan W, Coskun PE, Vesa J, Gold JA, Jiang YH, Potluri P, Procaccio V, Acab A, Weiss JH, Wallace DC, Kimonis VE. Mitochondrial dysfunction in CA1 hippocampal neurons of the UBE3A deficient mouse model for Angelman syndrome. Neurosci Lett. 2009 Jun 27. [Epub ahead of print] Free PMC Article.
Brandon MC, Wallace DC, Baldi P. Data structures and compression algorithms for genomic sequence data. Bioinformatics. 2009 Jul 15;25(14):1731-8. Epub 2009 May 15. Free PMC Article
Suissa S, Wang Z, Poole J, Wittkopp S, Feder J, Shutt TE, Wallace DC, Shadel GS, Mishmar D. Ancient mtDNA genetic variants modulate mtDNA transcription and replication. PLoS Genet. 2009 May;5(5):e1000474. Epub 2009 May 8. Free PMC Article.
Atilano SR, Chwa M, Kim DW, Jordan N, Udar N, Coskun P, Jester JV, Wallace DC, Kenney MC. Hydrogen peroxide causes mitochondrial DNA damage in corneal epithelial cells. Cornea. 2009 May;28(4):426-33.
Lee J, Schriner SE, Wallace DC. Adenine nucleotide translocator 1 deficiency increases resistance of mouse brain and neurons to excitotoxic insults. Biochim Biophys Acta. 2009 May;1787(5):364-70. Epub 2009 Jan 30.
Hendrickson SL, Kingsley LA, Ruiz-Pesini E, Poole JC, Jacobson LP, Palella FJ, Bream JH, Wallace DC, O'Brien SJ. Mitochondrial DNA haplogroups influence lipoatrophy after highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):111-6. Free PMC Article.
Rollins B, Martin MV, Sequeira PA, Moon EA, Morgan LZ, Watson SJ, Schatzberg A, Akil H, Myers RM, Jones EG, Wallace DC, Bunney WE, Vawter MP. Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder. PLoS One. 2009;4(3):e4913. Epub 2009 Mar 17. Free PMC Article.
Tang S, Le PK, Tse S, Wallace DC, Huang T. Heterozygous mutation of Opa1 in Drosophila shortens lifespan mediated through increased reactive oxygen species production. PLoS One. 2009;4(2):e4492. Epub 2009 Feb 16. Free PMC Article.
Potluri P, Davila A, Ruiz-Pesini E, Mishmar D, O'Hearn S, Hancock S, Simon M, Scheffler IE, Wallace DC, Procaccio V. A novel NDUFA1 mutation leads to a progressive mitochondrial complex I-specific neurodegenerative disease. Mol Genet Metab. 2009 Apr;96(4):189-95. Epub 2009 Jan 29.
Udar N, Atilano SR, Memarzadeh M, Boyer DS, Chwa M, Lu S, Maguen B, Langberg J, Coskun P, Wallace DC, Nesburn AB, Khatibi N, Hertzog D, Le K, Hwang D, Kenney MC. Mitochondrial DNA haplogroups associated with age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2966-74. Epub 2009 Jan 17. Free Article.
2008
Hendrickson SL, Hutcheson HB, Ruiz-Pesini E, Poole JC, Lautenberger J, Sezgin E, Kingsley L, Goedert JJ, Vlahov D, Donfield S, Wallace DC, O'Brien SJ. Mitochondrial DNA haplogroups influence AIDS progression. AIDS. 2008 Nov 30;22(18):2429-39. Free PMC Article.
Brandon MC, Ruiz-Pesini E, Mishmar D, Procaccio V, Lott MT, Nguyen KC, Spolim S, Patil U, Baldi P, Wallace DC. MITOMASTER: a bioinformatics tool for the analysis of mitochondrial DNA sequences. Hum Mutat. 2009 Jan;30(1):1-6.
Wallace DC. Mitochondria as chi. Genetics. 2008 Jun;179(2):727-35. Review. No abstract available. Free PMC Article.
Volodko NV, Starikovskaya EB, Mazunin IO, Eltsov NP, Naidenko PV, Wallace DC, Sukernik RI. Mitochondrial genome diversity in arctic Siberians, with particular reference to the evolutionary history of Beringia and Pleistocenic peopling of the Americas. Am J Hum Genet. 2008 May;82(5):1084-100. Epub 2008 May 1. Free PMC Article.
Subramaniam V, Golik P, Murdock DG, Levy S, Kerstann KW, Coskun PE, Melkonian GA, Wallace DC. MITOCHIP assessment of differential gene expression in the skeletal muscle of Ant1 knockout mice: coordinate regulation of OXPHOS, antioxidant, and apoptotic genes. Biochim Biophys Acta. 2008 Jul-Aug;1777(7-8):666-75. Epub 2008 Mar 28.
Fan W, Waymire KG, Narula N, Li P, Rocher C, Coskun PE, Vannan MA, Narula J, Macgregor GR, Wallace DC. A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations. Science. 2008 Feb 15;319(5865):958-62. Free Article.
Yarosh W, Monserrate J, Tong JJ, Tse S, Le PK, Nguyen K, Brachmann CB, Wallace DC, Huang T. The molecular mechanisms of OPA1-mediated optic atrophy in Drosophila model and prospects for antioxidant treatment. PLoS Genet. 2008 Jan;4(1):e6. Free PMC Article.
2007
Bannwarth S, Procaccio V, Rouzier C, Fragaki K, Poole J, Chabrol B, Desnuelle C, Pouget J, Azulay JP, Attarian S, Pellissier JF, Gargus JJ, Abdenur JE, Mozaffar T, Calvas P, Labauge P, Pages M, Wallace DC, Lambert JC, Paquis-Flucklinger V. Rapid identification of mitochondrial DNA (mtDNA) mutations in neuromuscular disorders by using surveyor strategy. Mitochondrion. 2008 Mar;8(2):136-45. Epub 2007 Nov 6.
Wallace DC. Why do we still have a maternally inherited mitochondrial DNA? Insights from evolutionary medicine. Annu Rev Biochem. 2007;76:781-821. Review.
Tong JJ, Schriner SE, McCleary D, Day BJ, Wallace DC. Life extension through neurofibromin mitochondrial regulation and antioxidant therapy for neurofibromatosis-1 in Drosophila melanogaster. Nat Genet. 2007 Apr;39(4):476-85. Epub 2007 Mar 18.
Ruiz-Pesini E, Lott MT, Procaccio V, Poole JC, Brandon MC, Mishmar D, Yi C, Kreuziger J, Baldi P, Wallace DC. An enhanced MITOMAP with a global mtDNA mutational phylogeny. Nucleic Acids Res. 2007 Jan;35(Database issue):D823-8. Epub 2006 Dec 18. Free PMC Article.