Emily Hodges
Faculty Member
Last active: 4/26/2017


Research in the Hodges Lab strives to understand how epigenetic features shape human genomes. We study this relationship on two levels; first, we are interested in how DNA methylation states are established in differentiating cells. Second, we are interested in the relationship between genotype and DNA methylation state (epitype). 

I. DNA methylation of functional elements in differentiating cells

Cis-regulatory elements such as enhancers are docking sites for transcription factors that control gene expression. They are the nodes of complex gene interaction networks that direct cell fate specification and maintain tissue homeostasis. Furthermore, they are believed to be a driving force behind the diversification of organisms. We have shown that enhancers progressively lose DNA methylation during cell fate specification. This process is accompanied by increased DNase hypersensitivity, post-translational modification of histones associated with active transcription, as well as the production of non-coding transcripts (eRNAs) within the enhancer element itself. In embryonic stem cells, many pre-established DHS regions remain methylated, suggesting that enhancer activation is sequential and DNA demethylation is secondary to chromatin remodeling. The order of these activities during differentiation is not well understood. Projects in our lab address these questions utilizing innovative biochemical, functional genomic and bioinformatic approaches.

 II. Human methylation variation and disease susceptibility

Enhancers display higher DNA methylation variability between species and human individuals than other genomic elements. These differential patterns of enhancer methylation may reflect individual differences in gene regulation and disease susceptibility. Central to this observation is the proposition that genotype and methylation state are strongly linked, and methylation changes that accompany genetic modifications could be used to infer the status of the enhancer. Understanding the genetic determinants that promote cell-type specific methylation patterns are vital to interpreting how changes in changes in DNA methylation patterns result in gene expression differences. Therefore, projects in our lab aim to investigate the interplay between sequence plasticity and methylation state, and to test the functional impact of this variation on gene regulatory activity.



The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. The evolutionary and phylogeographic history of woolly mammoths: a comprehensive mitogenomic analysis. Chang D, Knapp M, Enk J, Lippold S, Kircher M, Lister A, MacPhee RD, Widga C, Czechowski P, Sommer R, Hodges E, Stümpel N, Barnes I, Dalén L, Derevianko A, Germonpré M, Hillebrand-Voiculescu A, Constantin S, Kuznetsova T, Mol D, Rathgeber T, Rosendahl W, Tikhonov AN, Willerslev E, Hannon G, Lalueza-Fox C, Joger U, Poinar H, Hofreiter M, Shapiro B (2017) Sci Rep : 44585
    › Primary publication · 28327635 (PubMed) · PMC5361112 (PubMed Central)
  2. Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma. McFadden DG, Politi K, Bhutkar A, Chen FK, Song X, Pirun M, Santiago PM, Kim-Kiselak C, Platt JT, Lee E, Hodges E, Rosebrock AP, Bronson RT, Socci ND, Hannon GJ, Jacks T, Varmus H (2016) Proc Natl Acad Sci U S A 113(42): E6409-E6417
    › Primary publication · 27702896 (PubMed) · PMC5081629 (PubMed Central)
  3. An epigenetic memory of pregnancy in the mouse mammary gland. Dos Santos CO, Dolzhenko E, Hodges E, Smith AD, Hannon GJ (2015) Cell Rep 11(7): 1102-9
    › Primary publication · 25959817 (PubMed) · PMC4439279 (PubMed Central)
  4. Two ancient human genomes reveal Polynesian ancestry among the indigenous Botocudos of Brazil. Malaspinas AS, Lao O, Schroeder H, Rasmussen M, Raghavan M, Moltke I, Campos PF, Sagredo FS, Rasmussen S, Gonçalves VF, Albrechtsen A, Allentoft ME, Johnson PL, Li M, Reis S, Bernardo DV, DeGiorgio M, Duggan AT, Bastos M, Wang Y, Stenderup J, Moreno-Mayar JV, Brunak S, Sicheritz-Ponten T, Hodges E, Hannon GJ, Orlando L, Price TD, Jensen JD, Nielsen R, Heinemeier J, Olsen J, Rodrigues-Carvalho C, Lahr MM, Neves WA, Kayser M, Higham T, Stoneking M, Pena SD, Willerslev E (2014) Curr Biol 24(21): R1035-7
    › Primary publication · 25455029 (PubMed) · PMC4370112 (PubMed Central)
  5. Two waves of de novo methylation during mouse germ cell development. Molaro A, Falciatori I, Hodges E, Aravin AA, Marran K, Rafii S, McCombie WR, Smith AD, Hannon GJ (2014) Genes Dev 28(14): 1544-9
    › Primary publication · 25030694 (PubMed) · PMC4102761 (PubMed Central)
  6. De novo DNA demethylation and noncoding transcription define active intergenic regulatory elements. Schlesinger F, Smith AD, Gingeras TR, Hannon GJ, Hodges E (2013) Genome Res 23(10): 1601-14
    › Primary publication · 23811145 (PubMed) · PMC3787258 (PubMed Central)
  7. Variations in COL15A1 and COL18A1 influence age of onset of primary open angle glaucoma. Wiggs JL, Howell GR, Linkroum K, Abdrabou W, Hodges E, Braine CE, Pasquale LR, Hannon GJ, Haines JL, John SW (2013) Clin Genet 84(2): 167-74
    › Primary publication · 23621901 (PubMed) · PMC3771394 (PubMed Central)
  8. Site identification in high-throughput RNA-protein interaction data. Uren PJ, Bahrami-Samani E, Burns SC, Qiao M, Karginov FV, Hodges E, Hannon GJ, Sanford JR, Penalva LO, Smith AD (2012) Bioinformatics 28(23): 3013-20
    › Primary publication · 23024010 (PubMed) · PMC3509493 (PubMed Central)
  9. Genomic landscape of human allele-specific DNA methylation. Fang F, Hodges E, Molaro A, Dean M, Hannon GJ, Smith AD (2012) Proc Natl Acad Sci U S A 109(19): 7332-7
    › Primary publication · 22523239 (PubMed) · PMC3358917 (PubMed Central)
  10. Sperm methylation profiles reveal features of epigenetic inheritance and evolution in primates. Molaro A, Hodges E, Fang F, Song Q, McCombie WR, Hannon GJ, Smith AD (2011) Cell 146(6): 1029-41
    › Primary publication · 21925323 (PubMed) · PMC3205962 (PubMed Central)
  11. Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment. Hodges E, Molaro A, Dos Santos CO, Thekkat P, Song Q, Uren PJ, Park J, Butler J, Rafii S, McCombie WR, Smith AD, Hannon GJ (2011) Mol Cell 44(1): 17-28
    › Primary publication · 21924933 (PubMed) · PMC3412369 (PubMed Central)
  12. Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Erlich Y, Edvardson S, Hodges E, Zenvirt S, Thekkat P, Shaag A, Dor T, Hannon GJ, Elpeleg O (2011) Genome Res 21(5): 658-64
    › Primary publication · 21487076 (PubMed) · PMC3083082 (PubMed Central)
  13. Mutations in the RNA granule component TDRD7 cause cataract and glaucoma. Lachke SA, Alkuraya FS, Kneeland SC, Ohn T, Aboukhalil A, Howell GR, Saadi I, Cavallesco R, Yue Y, Tsai AC, Nair KS, Cosma MI, Smith RS, Hodges E, Alfadhli SM, Al-Hajeri A, Shamseldin HE, Behbehani A, Hannon GJ, Bulyk ML, Drack AV, Anderson PJ, John SW, Maas RL (2011) Science 331(6024): 1571-6
    › Primary publication · 21436445 (PubMed) · PMC3279122 (PubMed Central)
  14. Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection. Albert FW, Hodges E, Jensen JD, Besnier F, Xuan Z, Rooks M, Bhattacharjee A, Brizuela L, Good JM, Green RE, Burbano HA, Plyusnina IZ, Trut L, Andersson L, Schöneberg T, Carlborg O, Hannon GJ, Pääbo S (2011) Heredity (Edinb) 107(3): 205-14
    › Primary publication · 21304545 (PubMed) · PMC3183948 (PubMed Central)
  15. Targeted enrichment of specific regions in the human genome by array hybridization. Igartua C, Turner EH, Ng SB, Hodges E, Hannon GJ, Bhattacharjee A, Rieder MJ, Nickerson DA, Shendure J (2010) Curr Protoc Hum Genet : Unit 18.3
    › Primary publication · 20582915 (PubMed) · PMC2910258 (PubMed Central)
  16. Targeted investigation of the Neandertal genome by array-based sequence capture. Burbano HA, Hodges E, Green RE, Briggs AW, Krause J, Meyer M, Good JM, Maricic T, Johnson PL, Xuan Z, Rooks M, Bhattacharjee A, Brizuela L, Albert FW, de la Rasilla M, Fortea J, Rosas A, Lachmann M, Hannon GJ, Pääbo S (2010) Science 328(5979): 723-5
    › Primary publication · 20448179 (PubMed) · PMC3140021 (PubMed Central)
  17. Deep sequencing of target linkage assay-identified regions in familial breast cancer: methods, analysis pipeline and troubleshooting. Rosa-Rosa JM, Gracia-Aznárez FJ, Hodges E, Pita G, Rooks M, Xuan Z, Bhattacharjee A, Brizuela L, Silva JM, Hannon GJ, Benitez J (2010) PLoS One 5(4): e9976
    › Primary publication · 20368986 (PubMed) · PMC2848842 (PubMed Central)
  18. Evolutionary flux of canonical microRNAs and mirtrons in Drosophila. Berezikov E, Liu N, Flynt AS, Hodges E, Rooks M, Hannon GJ, Lai EC (2010) Nat Genet 42(1): 6-9; author reply 9-10
    › Primary publication · 20037610 (PubMed) · PMC4136759 (PubMed Central)
  19. High definition profiling of mammalian DNA methylation by array capture and single molecule bisulfite sequencing. Hodges E, Smith AD, Kendall J, Xuan Z, Ravi K, Rooks M, Zhang MQ, Ye K, Bhattacharjee A, Brizuela L, McCombie WR, Wigler M, Hannon GJ, Hicks JB (2009) Genome Res 19(9): 1593-605
    › Primary publication · 19581485 (PubMed) · PMC2752124 (PubMed Central)
  20. Hybrid selection of discrete genomic intervals on custom-designed microarrays for massively parallel sequencing. Hodges E, Rooks M, Xuan Z, Bhattacharjee A, Benjamin Gordon D, Brizuela L, Richard McCombie W, Hannon GJ (2009) Nat Protoc 4(6): 960-74
    › Primary publication · 19478811 (PubMed) · PMC2990409 (PubMed Central)
  21. Exploring the foundation of genomics: a northern blot reference set for the comparative analysis of transcript profiling technologies. Kemmer D, Faxén M, Hodges E, Lim J, Herzog E, Ljungström E, Lundmark A, Olsen MK, Podowski R, Sonnhammer EL, Nilsson P, Reimers M, Lenhard B, Roberds SL, Wahlestedt C, Höög C, Agarwal P, Wasserman WW (2004) Comp Funct Genomics 5(8): 584-95
    › Primary publication · 18629180 (PubMed) · PMC2447472 (PubMed Central)
  22. Conservation of small RNA pathways in platypus. Murchison EP, Kheradpour P, Sachidanandam R, Smith C, Hodges E, Xuan Z, Kellis M, Grützner F, Stark A, Hannon GJ (2008) Genome Res 18(6): 995-1004
    › Primary publication · 18463306 (PubMed) · PMC2413167 (PubMed Central)
  23. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Tam OH, Aravin AA, Stein P, Girard A, Murchison EP, Cheloufi S, Hodges E, Anger M, Sachidanandam R, Schultz RM, Hannon GJ (2008) Nature 453(7194): 534-8
    › Primary publication · 18404147 (PubMed) · PMC2981145 (PubMed Central)
  24. Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5' terminal nucleotide. Mi S, Cai T, Hu Y, Chen Y, Hodges E, Ni F, Wu L, Li S, Zhou H, Long C, Chen S, Hannon GJ, Qi Y (2008) Cell 133(1): 116-27
    › Primary publication · 18342361 (PubMed) · PMC2981139 (PubMed Central)
  25. Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures. Stark A, Lin MF, Kheradpour P, Pedersen JS, Parts L, Carlson JW, Crosby MA, Rasmussen MD, Roy S, Deoras AN, Ruby JG, Brennecke J, Harvard FlyBase curators, Berkeley Drosophila Genome Project, Hodges E, Hinrichs AS, Caspi A, Paten B, Park SW, Han MV, Maeder ML, Polansky BJ, Robson BE, Aerts S, van Helden J, Hassan B, Gilbert DG, Eastman DA, Rice M, Weir M, Hahn MW, Park Y, Dewey CN, Pachter L, Kent WJ, Haussler D, Lai EC, Bartel DP, Hannon GJ, Kaufman TC, Eisen MB, Clark AG, Smith D, Celniker SE, Gelbart WM, Kellis M (2007) Nature 450(7167): 219-32
    › Primary publication · 17994088 (PubMed) · PMC2474711 (PubMed Central)
  26. Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes. Stark A, Kheradpour P, Parts L, Brennecke J, Hodges E, Hannon GJ, Kellis M (2007) Genome Res 17(12): 1865-79
    › Primary publication · 17989255 (PubMed) · PMC2099594 (PubMed Central)
  27. Genome-wide in situ exon capture for selective resequencing. Hodges E, Xuan Z, Balija V, Kramer M, Molla MN, Smith SW, Middle CM, Rodesch MJ, Albert TJ, Hannon GJ, McCombie WR (2007) Nat Genet 39(12): 1522-7
    › Primary publication · 17982454 (PubMed)
  28. NovelFam3000--uncharacterized human protein domains conserved across model organisms. Kemmer D, Podowski RM, Arenillas D, Lim J, Hodges E, Roth P, Sonnhammer EL, Höög C, Wasserman WW (2006) BMC Genomics : 48
    › Primary publication · 16533400 (PubMed) · PMC1440326 (PubMed Central)
  29. Thorough validation of siRNA-induced cell death phenotypes defines new anti-apoptotic protein. Wu W, Hodges E, Höög C (2006) Nucleic Acids Res 34(2): e13
    › Primary publication · 16432257 (PubMed) · PMC1345702 (PubMed Central)
  30. Accelerated discovery of novel protein function in cultured human cells. Hodges E, Redelius JS, Wu W, Höög C (2005) Mol Cell Proteomics 4(9): 1319-27
    › Primary publication · 15965266 (PubMed)
  31. A novel approach for evaluating the efficiency of siRNAs on protein levels in cultured cells. Wu W, Hodges E, Redelius J, Höög C (2004) Nucleic Acids Res 32(2): e17
    › Primary publication · 14739231 (PubMed) · PMC373369 (PubMed Central)