Vanderbilt University School of Medicine

Samuels, David Charles , PhD
Associate Professor of Molecular Physiology and Biophysics

Lab Url:

Phone Number: 615-343-7870


Samuels, David's picture

Office Address   Mailing Address

507B Light Hall

507B Light Hall 37232

Research Keywords
mitochondria, mtDNA, polymerase gamma, mitochondrial toxicity, mitochondrial genetics, mitochondrial disease,DNA synthesis,DRUG metabolism,Genetics,Genome,Human Genetics,Infectious disease,Mutation,Neuroscience,Physiology

Research Specialty
Mitochondrial genetics and diseases. Toxicity mechanisms of HIV treatment. Pathogenesis of protein variations.

Research Description
The Samuels group uses computational methods for research on mitochondrial biology and disease. These methods range from biochemical simulations to genetic sequence analysis to clinical data analysis. We collaborate with clinicians and wet-lab biologists.

Our group is applying full-sequence analysis methods to determine the role of mitochondrial DNA variations on various diseases. These include the toxicity of HIV drugs, neurodegenerative diseases, and other phenotypes.

Eilertson, B, Maruri, F, Blackman, A, Herrera, M, Samuels, DC, Sterling, TR. High proportion of heteroresistance in gyrA and gyrB in fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates. Antimicrob Agents Chemother, 58(6), 3270-5, 2014.

Estopinal, CB, Chocron, IM, Parks, MB, Wade, EA, Roberson, RM, Burgess, LG, Brantley, MA, Samuels, DC. Mitochondrial haplogroups are associated with severity of diabetic retinopathy. Invest Ophthalmol Vis Sci, 55(9), 5589-95, 2014.

Guo, Y, He, J, Zhao, S, Wu, H, Zhong, X, Sheng, Q, Samuels, DC, Shyr, Y, Long, J. Illumina human exome genotyping array clustering and quality control. Nat Protoc, 9(11), 2643-62, 2014.

Kallianpur, AR, Jia, P, Ellis, RJ, Zhao, Z, Bloss, C, Wen, W, Marra, CM, Hulgan, T, Simpson, DM, Morgello, S, McArthur, JC, Clifford, DB, Collier, AC, Gelman, BB, McCutchan, JA, Franklin, D, Samuels, DC, Rosario, D, Holzinger, E, Murdock, DG, Letendre, S, Grant, I, , . Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy. PLoS One, 9(8), e103123, 2014.

Pereira, L, Soares, P, Triska, P, Rito, T, van der Waerden, A, Li, B, Radivojac, P, Samuels, DC. Global human frequencies of predicted nuclear pathogenic variants and the role played by protein hydrophobicity in pathogenicity potential. Sci Rep, 4, 7155, 2014.

Steffann, J, Gigarel, N, Samuels, DC, Monnot, S, Borghese, R, Hesters, L, Frydman, N, Burlet, P, Frydman, R, Benachi, A, Rotig, A, Munnich, A, Bonnefont, JP. Data from artificial models of mitochondrial DNA disorders are not always applicable to humans. Cell Rep, 7(4), 933-4, 2014.

Wang, J, Raskin, L, Samuels, DC, Shyr, Y, Guo, Y. Genome measures used for quality control are dependent on gene function and ancestry. Bioinformatics, , , 2014.

Ye, F, Samuels, DC, Clark, T, Guo, Y. High-throughput sequencing in mitochondrial DNA research. Mitochondrion, 17, 157-63, 2014.

Guo, Y, Li, J, Li, CI, Shyr, Y, Samuels, DC. MitoSeek: extracting mitochondria information and performing high-throughput mitochondria sequencing analysis. Bioinformatics, 29(9), 1210-1, 2013.

Guo, Y, Samuels, DC, Li, J, Clark, T, Li, CI, Shyr, Y. Evaluation of allele frequency estimation using pooled sequencing data simulation. ScientificWorldJournal, 2013, 895496, 2013.

Guo, Y, Sheng, Q, Li, J, Ye, F, Samuels, DC, Shyr, Y. Large scale comparison of gene expression levels by microarrays and RNAseq using TCGA data. PLoS One, 8(8), e71462, 2013.

Guo, Y, Sheng, Q, Samuels, DC, Lehmann, B, Bauer, JA, Pietenpol, J, Shyr, Y. Comparative study of exome copy number variation estimation tools using array comparative genomic hybridization as control. Biomed Res Int, 2013, 915636, 2013.

Guo, Y, Zhao, S, Sheng, Q, Ye, F, Li, J, Lehmann, B, Pietenpol, J, Samuels, DC, Shyr, Y. Multi-perspective quality control of Illumina exome sequencing data using QC3. Genomics, 103(5-6), 323-8, 2013.

Hart, AB, Samuels, DC, Hulgan, T. The other genome: a systematic review of studies of mitochondrial DNA haplogroups and outcomes of HIV infection and antiretroviral therapy. AIDS Rev, 15(4), 213-20, 2013.

Samuels, DC, Han, L, Li, J, Quanghu, S, Clark, TA, Shyr, Y, Guo, Y. Finding the lost treasures in exome sequencing data. Trends Genet, 29(10), 593-9, 2013.

Samuels, DC, Li, C, Li, B, Song, Z, Torstenson, E, Boyd Clay, H, Rokas, A, Thornton-Wells, TA, Moore, JH, Hughes, TM, Hoffman, RD, Haines, JL, Murdock, DG, Mortlock, DP, Williams, SM. Recurrent tissue-specific mtDNA mutations are common in humans. PLoS Genet, 9(11), e1003929, 2013.

Samuels, DC, Wonnapinij, P, Chinnery, PF. Preventing the transmission of pathogenic mitochondrial DNA mutations: Can we achieve long-term benefits from germ-line gene transfer. Hum Reprod, 28(3), 554-9, 2013.

Chinnery, PF, Elliott, HR, Hudson, G, Samuels, DC, Relton, CL. Epigenetics, epidemiology and mitochondrial DNA diseases. Int J Epidemiol, , , 2012.

Gandhi, VV, Samuels, DC. Correlated Tissue Expression of Genes of Cytoplasmic and Mitochondrial Nucleotide Metabolisms in Normal Tissues is Disrupted in Transformed Tissues. Nucleosides Nucleotides Nucleic Acids, 31(2), 112-29, 2012.

Guo, Y, Li, J, Li, CI, Long, J, Samuels, DC, Shyr, Y. The effect of strand bias in Illumina short-read sequencing data. BMC Genomics, 13, 666, 2012.

Holzinger, ER, Hulgan, T, Ellis, RJ, Samuels, DC, Ritchie, MD, Haas, DW, Kallianpur, AR, Bloss, CS, Clifford, DB, Collier, AC, Gelman, BB, Marra, CM, McArthur, JC, McCutchan, JA, Morgello, S, Simpson, DM, Franklin, DR, Rosario, D, Selph, D, Letendre, S, Grant, I, , . Mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER. J Neurovirol, 18(6), 511-20, 2012.

Hulgan, T, Robbins, GK, Kalams, SA, Samuels, DC, Grady, B, Shafer, R, Murdock, DG, Selph, D, Haas, DW, Pollard, RB, , . T cell activation markers and African mitochondrial DNA haplogroups among non-Hispanic black participants in AIDS clinical trials group study 384. PLoS One, 7(8), e43803, 2012.

Gandhi, VV, Samuels, DC. Enzyme kinetics of the mitochondrial deoxyribonucleoside salvage pathway are not sufficient to support rapid mtDNA replication. PLoS Comput Biol, 7(8), e1002078, 2011. PMCID:3150320

Gandhi, VV, Samuels, DC. A review comparing deoxyribonucleoside triphosphate (dNTP) concentrations in the mitochondrial and cytoplasmic compartments of normal and transformed cells. Nucleosides Nucleotides Nucleic Acids, 30(5), 317-39, 2011. PMCID:3210641

Grady, BJ, Samuels, DC, Robbins, GK, Selph, D, Canter, JA, Pollard, RB, Haas, DW, Shafer, R, Kalams, SA, Murdock, DG, Ritchie, MD, Hulgan, T, , . Mitochondrial genomics and CD4 T-cell count recovery after antiretroviral therapy initiation in AIDS clinical trials group study 384. J Acquir Immune Defic Syndr, 58(4), 363-70, 2011. PMCID:3204178

Song, Z, Cao, Y, Samuels, DC. Replication pauses of the wild-type and mutant mitochondrial DNA polymerase gamma: a simulation study. PLoS Comput Biol, 7(11), e1002287, 2011. PMCID:3219627

Marchington, D, Malik, S, Banerjee, A, Turner, K, Samuels, D, Macaulay, V, Oakeshott, P, Fratter, C, Kennedy, S, Poulton, J. Information for genetic management of mtDNA disease: sampling pathogenic mtDNA mutants in the human germline and in placenta. J Med Genet, 47(4), 257-61, 2010. PMCID:2813015

Samuels, DC, Wonnapinij, P, Cree, LM, Chinnery, PF. Reassessing evidence for a postnatal mitochondrial genetic bottleneck. Nat Genet, 42(6), 471-2; author reply 472-3, 2010.

Song, Z, Samuels, DC. Analysis of enzyme kinetic data for mtDNA replication. Methods, 51(4), 385-91, 2010. PMCID:2901142

Wonnapinij, P, Chinnery, PF, Samuels, DC. Previous estimates of mitochondrial DNA mutation level variance did not account for sampling error: comparing the mtDNA genetic bottleneck in mice and humans. Am J Hum Genet, 86(4), 540-50, 2010. PMCID:2901142

Yu-Wai-Man, P, Sitarz, KS, Samuels, DC, Griffiths, PG, Reeve, AK, Bindoff, LA, Horvath, R, Chinnery, PF. OPA1 mutations cause cytochrome c oxidase deficiency due to loss of wild-type mtDNA molecules. Hum Mol Genet, 19(15), 3043-52, 2010. PMCID:2901142

Cao, Y, Samuels, DC. Discrete stochastic simulation methods for chemically reacting systems. Methods Enzymol, 454, 115-40, 2009.

Cree, LM, Samuels, DC, Chinnery, PF. The inheritance of pathogenic mitochondrial DNA mutations. Biochim Biophys Acta, , , 2009.

Guan, X, Silva, P, Gyenai, KB, Xu, J, Geng, T, Tu, Z, Samuels, DC, Smith, EJ. The mitochondrial genome sequence and molecular phylogeny of the turkey, Meleagris gallopavo. Anim Genet, 40(2), 134-41, 2009. PMCID:2664387

Pereira, L, Freitas, F, Fernandes, V, Pereira, JB, Costa, MD, Costa, S, M?!ximo, V, Macaulay, V, Rocha, R, Samuels, DC. The diversity present in 5140 human mitochondrial genomes. Am J Hum Genet, 84(5), 628-40, 2009. PMCID:2681004

Samuels, DC, Burn, DJ, Chinnery, PF. Detecting new neurodegenerative disease genes: does phenotype accuracy limit the horizon. Trends Genet, 25(11), 486-8, 2009. PMCID:2824109

Wendelsdorf, KV, Song, Z, Cao, Y, Samuels, DC. An analysis of enzyme kinetics data for mitochondrial DNA strand termination by nucleoside reverse transcription inhibitors. PLoS Comput Biol, 5(1), e1000261, 2009. PMCID:2603287

Cree, LM, Samuels, DC, de Sousa Lopes, SC, Rajasimha, HK, Wonnapinij, P, Mann, JR, Dahl, HH, Chinnery, PF. A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat Genet, 40(2), 249-54, 2008.

Elliott, HR, Samuels, DC, Eden, JA, Relton, CL, Chinnery, PF. Pathogenic mitochondrial DNA mutations are common in the general population. Am J Hum Genet, 83(2), 254-60, 2008. PMCID:2495064

Kang, J, Samuels, DC. The evidence that the DNC (SLC25A19) is not the mitochondrial deoxyribonucleotide carrier. Mitochondrion, 8(2), 103-8, 2008.

Krishnan, KJ, Reeve, AK, Samuels, DC, Chinnery, PF, Blackwood, JK, Taylor, RW, Wanrooij, S, Spelbrink, JN, Lightowlers, RN, Turnbull, DM. What causes mitochondrial DNA deletions in human cells. Nat Genet, 40(3), 275-9, 2008.

Pereira, F, Soares, P, Carneiro, J, Pereira, L, Richards, MB, Samuels, DC, Amorim, A. Evidence for variable selective pressures at a large secondary structure of the human mitochondrial DNA control region. Mol Biol Evol, 25(12), 2759-70, 2008.

Rajasimha, HK, Chinnery, PF, Samuels, DC. Selection against pathogenic mtDNA mutations in a stem cell population leads to the loss of the 3243A-->G mutation in blood. Am J Hum Genet, 82(2), 333-43, 2008. PMCID:2427290

Wonnapinij, P, Chinnery, PF, Samuels, DC. The distribution of mitochondrial DNA heteroplasmy due to random genetic drift. Am J Hum Genet, 83(5), 582-93, 2008. PMCID:2668051

Durham, SE, Samuels, DC, Cree, LM, Chinnery, PF. Normal levels of wild-type mitochondrial DNA maintain cytochrome c oxidase activity for two pathogenic mitochondrial DNA mutations but not for m.3243A-->G. Am J Hum Genet, 81(1), 189-95, 2007. PMCID:1950909

Pyle, A, Taylor, RW, Durham, SE, Deschauer, M, Schaefer, AM, Samuels, DC, Chinnery, PF. Depletion of mitochondrial DNA in leucocytes harbouring the 3243A->G mtDNA mutation. J Med Genet, 44(1), 69-74, 2007.

Samuels, DC. Computational models of antiviral toxicity. Curr Opin Drug Discov Devel, 10(1), 43-8, 2007.

Durham, SE, Samuels, DC, Chinnery, PF. Is selection required for the accumulation of somatic mitochondrial DNA mutations in post-mitotic cells. Neuromuscul Disord, 16(6), 381-6, 2006.

Samuels, DC. Mitochondrial AZT metabolism. IUBMB Life, 58(7), 403-8, 2006.

Samuels, DC, Carothers, AD, Horton, R, Chinnery, PF. The power to detect disease associations with mitochondrial DNA haplogroups. Am J Hum Genet, 78(4), 713-20, 2006. PMCID:1424681

Bradshaw, PC, Li, J, Samuels, DC. A computational model of mitochondrial AZT metabolism. Biochem J, 392(Pt 2), 363-73, 2005. PMCID:1316272

Bradshaw, PC, Rathi, A, Samuels, DC. Mitochondrial-encoded membrane protein transcripts are pyrimidine-rich while soluble protein transcripts and ribosomal RNA are purine-rich. BMC Genomics, 6, 136, 2005. PMCID:1262711

Bradshaw, PC, Samuels, DC. A computational model of mitochondrial deoxynucleotide metabolism and DNA replication. Am J Physiol Cell Physiol, 288(5), C989-1002, 2005.

Durham, SE, Bonilla, E, Samuels, DC, DiMauro, S, Chinnery, PF. Mitochondrial DNA copy number threshold in mtDNA depletion myopathy. Neurology, 65(3), 453-5, 2005.

Samuels, DC. Life span is related to the free energy of mitochondrial DNA. Mech Ageing Dev, 126(10), 1123-9, 2005.

Samuels, DC. Mitochondrial DNA repeats constrain the life span of mammals. Trends Genet, 20(5), 226-9, 2004.

Samuels, DC, Schon, EA, Chinnery, PF. Two direct repeats cause most human mtDNA deletions. Trends Genet, 20(9), 393-8, 2004.

Capps, GJ, Samuels, DC, Chinnery, PF. A model of the nuclear control of mitochondrial DNA replication. J Theor Biol, 221(4), 565-83, 2003.

Samuels, DC, Boys, RJ, Henderson, DA, Chinnery, PF. A compositional segmentation of the human mitochondrial genome is related to heterogeneities in the guanine mutation rate. Nucleic Acids Res, 31(20), 6043-52, 2003. PMCID:219467

Taylor, RW, Barron, MJ, Borthwick, GM, Gospel, A, Chinnery, PF, Samuels, DC, Taylor, GA, Plusa, SM, Needham, SJ, Greaves, LC, Kirkwood, TB, Turnbull, DM. Mitochondrial DNA mutations in human colonic crypt stem cells. J Clin Invest, 112(9), 1351-60, 2003. PMCID:228466

Barenghi, CF, Hulton, S, Samuels, DC. Polarization of superfluid turbulence. Phys Rev Lett, 89(27), 275301, 2002.

Barenghi, CF, Samuels, DC. Evaporation of a packet of quantized vorticity. Phys Rev Lett, 89(15), 155302, 2002.

Chinnery, PF, Samuels, DC, Elson, J, Turnbull, DM. Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism. Lancet, 360(9342), 1323-5, 2002.

Elson, JL, Samuels, DC, Johnson, MA, Turnbull, DM, Chinnery, PF. The length of cytochrome c oxidase-negative segments in muscle fibres in patients with mtDNA myopathy. Neuromuscul Disord, 12(9), 858-64, 2002.

Brown, DT, Samuels, DC, Michael, EM, Turnbull, DM, Chinnery, PF. Random genetic drift determines the level of mutant mtDNA in human primary oocytes. Am J Hum Genet, 68(2), 533-6, 2001. PMCID:1235288

Elson, JL, Samuels, DC, Turnbull, DM, Chinnery, PF. Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age. Am J Hum Genet, 68(3), 802-6, 2001. PMCID:1274494

Kivotides, D, Barenghi, CF, Samuels, DC. Fractal dimension of superfluid turbulence. Phys Rev Lett, 87(15), 155301, 2001.

Kivotides, D, Vassilicos, JC, Barenghi, CF, Khan, MA, Samuels, DC. Quantum signature of superfluid turbulence. Phys Rev Lett, 87(27 Pt 1), 275302, 2001.

Kivotides, D, Vassilicos, JC, Samuels, DC, Barenghi, CF. Kelvin waves cascade in superfluid turbulence. Phys Rev Lett, 86(14), 3080-3, 2001.

Leadbeater, M, Winiecki, T, Samuels, DC, Barenghi, CF, Adams, CS. Sound emission due to superfluid vortex reconnections. Phys Rev Lett, 86(8), 1410-3, 2001.

Chinnery, PF, Thorburn, DR, Samuels, DC, White, SL, Dahl, HM, Turnbull, DM, Lightowlers, RN, Howell, N. The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both. Trends Genet, 16(11), 500-5, 2000.

Kivotides, D, Barenghi, CF, Samuels, DC. Triple vortex ring structure in superfluid helium II. Science, 290(5492), 777-9, 2000.

Chinnery, PF, Samuels, DC. Relaxed replication of mtDNA: A model with implications for the expression of disease. Am J Hum Genet, 64(4), 1158-65, 1999. PMCID:1377840

Miller, KE, Samuels, DC. The axon as a metabolic compartment: protein degradation, transport, and maximum length of an axon. J Theor Biol, 186(3), 373-9, 1997.

Samuels, DC, Hentschel, HG, Fine, A. The origin of neuronal polarization: a model of axon formation. Philos Trans R Soc Lond B Biol Sci, 351(1344), 1147-56, 1996.

Samuels, DC. Response of superfluid vortex filaments to concentrated normal-fluid vorticity. Phys Rev B Condens Matter, 47(2), 1107-1110, 1993.

Samuels, DC. Velocity matching and Poiseuille pipe flow of superfluid helium. Phys Rev B Condens Matter, 46(18), 11714-11724, 1992.

Samuels, DC, Donnelly, RJ. Motion of charged vortex rings in helium II. Phys Rev Lett, 67(18), 2505-2508, 1991.

Samuels, DC, Donnelly, RJ. Dynamics of the interactions of rotons with quantized vortices in helium II. Phys Rev Lett, 65(2), 187-190, 1990.

Samuels, DC, Donnelly, RJ. Sideband instability and recurrence of Kelvin waves on vortex cores. Phys Rev Lett, 64(12), 1385-1388, 1990.

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