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    Lilia Iakoucheva

    TitleAssociate Professor
    SchoolUniversity of California, San Diego
    DepartmentPsychiatry
    Address9500 Gilman Drive #0603
    CA La Jolla 92093
    Phone858-822-1878
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      Biography

      Dr. Lilia Iakoucheva obtained B.S. in genetics from Kiev State University (Kiev, Ukraine) and Ph.D. in molecular biology and immunology from the Institute of Immunology (Moscow, Russia). After completing postdoctoral training in protein biochemistry at the Pacific Northwest National Laboratory (Richland, WA) she joined the group of Prof. Keith Dunker to study intrinsically disordered proteins. During that time and with active Dr. Iakoucheva’s participation, the group made a series of fundamental discoveries about disordered proteins, including their role in cell signaling and cancer, the importance of disorder for post-translational modifications and for interactions with other proteins and ligands. In 2003, Dr. Iakoucheva joined the Rockefeller University (New York, NY) as a Research Assistant Professor, where she continued to investigate functional properties of disordered proteins, at the same time gradually shifting her interests into disease-oriented field. Rapid advancement in the disease gene discovery in the post-genomic era opened new avenues and opportunities for more detailed investigation of protein interaction networks and pathways underlying many human diseases. Dr. Iakoucheva became especially interested in the molecular basis of psychiatric diseases, which she began to explore using systems biology approaches. She joined the Psychiatry Department of the University of California San Diego (La Jolla, CA) as an Assistant Professor in 2010, where she continues to apply her experience in protein structure, disorder and protein-protein interactions analyses towards investigation of autism and schizophrenia. Dr. Iakoucheva has been the principal investigator on research grants from NSF, NCI, NICHD, and NIMH.

      Research Interests

      Dr. Iakoucheva’s research focuses on understanding of the molecular basis of autism and schizophrenia using systems biology approaches. Our aim is to discover functional protein interaction networks connecting seemingly unrelated candidate genes for psychiatric diseases. We are building comprehensive protein-protein interaction networks for autism and schizophrenia candidate genes and their splicing isoforms. In addition, we are integrating gene expression data with our experimentally derived networks to understand spatio-temporal dynamics of protein interactions in the brain. Our immediate goal is to investigate perturbations of the disease networks by the Copy Number Variants (CNVs) and protein-damaging Single Nucleotide Variants (SNVs) identified in the patients using the Whole Exome Sequencing (WES) studies. Additionally, we are interested in interpreting non-coding genetic variation with relevance to psychiatric diseases. We are investigating functional impact of UTR, promoter and splice site mutations identified in the Whole Genome Sequencing (WGS) studies of autism and schizophrenia using in vitro cellular systems.


      Collapse Research 
      Collapse Research Activities and Funding
      Integrative functional genomic study of pathways impacted by recurrent autism CNV
      NIH/NIMH R01MH108528Sep 1, 2016 - Jun 30, 2021
      Role: Principal Investigator
      Evaluating the effect of splicing mutations on isoform networks in autism
      NIH/NIMH R01MH109885May 1, 2016 - Feb 28, 2021
      Role: Principal Investigator
      A computational framework for predicting the impact of mutations in autism
      NIH/NIMH R01MH105524Sep 25, 2014 - Jul 31, 2017
      Role: Principal Investigator
      Protein network of high risk copy number variants for psychiatric disorders
      NIH/NIMH R21MH104766Jul 1, 2014 - Jun 30, 2016
      Role: Principal Investigator
      Schizophrenia interactome mapping and global discovery of brain splice variants
      NIH/NIMH R01MH091350May 20, 2010 - Mar 31, 2015
      Role: Principal Investigator
      A systems biology approach to unravel theunderlying functional modules of ASD
      NIH/NICHD R01HD065288Sep 30, 2009 - Aug 31, 2012
      Role: Principal Investigator
      Protein structural disorder and ubiquitination
      NIH/NCI R21CA113711Aug 2, 2007 - Jul 31, 2010
      Role: Principal Investigator

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      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Brandler WM, Antaki D, Gujral M, Noor A, Rosanio G, Chapman TR, Barrera DJ, Lin GN, Malhotra D, Watts AC, Wong LC, Estabillo JA, Gadomski TE, Hong O, Fajardo KV, Bhandari A, Owen R, Baughn M, Yuan J, Solomon T, Moyzis AG, Maile MS, Sanders SJ, Reiner GE, Vaux KK, Strom CM, Zhang K, Muotri AR, Akshoomoff N, Leal SM, Pierce K, Courchesne E, Iakoucheva L, Corsello C, Sebat J. Frequency and Complexity of De Novo Structural Mutation in Autism. Am J Hum Genet. 2016 Apr 7; 98(4):667-79. PMID: 27018473.
        View in: PubMed
      2. Yang X, Coulombe-Huntington J, Kang S, Sheynkman GM, Hao T, Richardson A, Sun S, Yang F, Shen YA, Murray RR, Spirohn K, Begg BE, Duran-Frigola M, MacWilliams A, Pevzner SJ, Zhong Q, Trigg SA, Tam S, Ghamsari L, Sahni N, Yi S, Rodriguez MD, Balcha D, Tan G, Costanzo M, Andrews B, Boone C, Zhou XJ, Salehi-Ashtiani K, Charloteaux B, Chen AA, Calderwood MA, Aloy P, Roth FP, Hill DE, Iakoucheva L, Xia Y, Vidal M. Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell. 2016 Feb 11; 164(4):805-17. PMID: 26871637.
        View in: PubMed
      3. Lin GN, Corominas R, Lemmens I, Yang X, Tavernier J, Hill DE, Vidal M, Sebat J, Iakoucheva L. Spatiotemporal 16p11.2 Protein Network Implicates Cortical Late Mid-Fetal Brain Development and KCTD13-Cul3-RhoA Pathway in Psychiatric Diseases. Neuron. 2015 Feb 18; 85(4):742-54. PMID: 25695269.
        View in: PubMed
      4. Rolland T, Ta An M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N, Yi S, Lemmens I, Fontanillo C, Mosca R, Kamburov A, Ghiassian SD, Yang X, Ghamsari L, Balcha D, Begg BE, Braun P, Brehme M, Broly MP, Carvunis AR, Convery-Zupan D, Corominas R, Coulombe-Huntington J, Dann E, Dreze M, Dricot A, Fan C, Franzosa E, Gebreab F, Gutierrez BJ, Hardy MF, Jin M, Kang S, Kiros R, Lin GN, Luck K, MacWilliams A, Menche J, Murray RR, Palagi A, Poulin MM, Rambout X, Rasla J, Reichert P, Romero V, Ruyssinck E, Sahalie JM, Scholz A, Shah AA, Sharma A, Shen Y, Spirohn K, Tam S, Tejeda AO, Trigg SA, Twizere JC, Vega K, Walsh J, Cusick ME, Xia Y, Barabási AL, Iakoucheva L, Aloy P, De Las Rivas J, Tavernier J, Calderwood MA, Hill DE, Hao T, Roth FP, Vidal M. A proteome-scale map of the human interactome network. Cell. 2014 Nov 20; 159(5):1212-26. PMID: 25416956.
        View in: PubMed
      5. Uversky VN, Davé V, Iakoucheva L, Malaney P, Metallo SJ, Pathak RR, Joerger AC. Pathological unfoldomics of uncontrolled chaos: intrinsically disordered proteins and human diseases. Chem Rev. 2014 Jul 9; 114(13):6844-79. PMID: 24830552.
        View in: PubMed
      6. Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, Broly M, Rodriguez M, Tam S, Trigg SA, Fan C, Yi S, Tasan M, Lemmens I, Kuang X, Zhao N, Malhotra D, Michaelson JJ, Vacic V, Calderwood MA, Roth FP, Tavernier J, Horvath S, Salehi-Ashtiani K, Korkin D, Sebat J, Hill DE, Hao T, Vidal M, Iakoucheva L. Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. Nat Commun. 2014; 5:3650. PMID: 24722188.
        View in: PubMed
      7. Dembinski H, Wismer K, Balasubramaniam D, Gonzalez HA, Alverdi V, Iakoucheva L, Komives EA. Predicted disorder-to-order transition mutations in I?Ba disrupt function. Phys Chem Chem Phys. 2014 Apr 14; 16(14):6480-5. PMID: 24605363.
        View in: PubMed
      8. Michaelson JJ, Shi Y, Gujral M, Zheng H, Malhotra D, Jin X, Jian M, Liu G, Greer D, Bhandari A, Wu W, Corominas R, Peoples A, Koren A, Gore A, Kang S, Lin GN, Estabillo J, Gadomski T, Singh B, Zhang K, Akshoomoff N, Corsello C, McCarroll S, Iakoucheva L, Li Y, Wang J, Sebat J. Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. Cell. 2012 Dec 21; 151(7):1431-42. PMID: 23260136.
        View in: PubMed
      9. Vacic V, Markwick PR, Oldfield CJ, Zhao X, Haynes C, Uversky VN, Iakoucheva L. Disease-associated mutations disrupt functionally important regions of intrinsic protein disorder. PLoS Comput Biol. 2012; 8(10):e1002709. PMID: 23055912.
        View in: PubMed
      10. Vacic V, Iakoucheva L. Disease mutations in disordered regions--exception to the rule? Mol Biosyst. 2012 Jan; 8(1):27-32. PMID: 22080206.
        View in: PubMed
      11. Vacic V, McCarthy S, Malhotra D, Murray F, Chou HH, Peoples A, Makarov V, Yoon S, Bhandari A, Corominas R, Iakoucheva L, Krastoshevsky O, Krause V, Larach-Walters V, Welsh DK, Craig D, Kelsoe JR, Gershon ES, Leal SM, Dell Aquila M, Morris DW, Gill M, Corvin A, Insel PA, McClellan J, King MC, Karayiorgou M, Levy DL, DeLisi LE, Sebat J. Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature. 2011 Mar 24; 471(7339):499-503. PMID: 21346763.
        View in: PubMed
      12. Mills RE, Walter K, Stewart C, Handsaker RE, Chen K, Alkan C, Abyzov A, Yoon SC, Ye K, Cheetham RK, Chinwalla A, Conrad DF, Fu Y, Grubert F, Hajirasouliha I, Hormozdiari F, Iakoucheva L, Iqbal Z, Kang S, Kidd JM, Konkel MK, Korn J, Khurana E, Kural D, Lam HY, Leng J, Li R, Li Y, Lin CY, Luo R, Mu XJ, Nemesh J, Peckham HE, Rausch T, Scally A, Shi X, Stromberg MP, Stütz AM, Urban AE, Walker JA, Wu J, Zhang Y, Zhang ZD, Batzer MA, Ding L, Marth GT, McVean G, Sebat J, Snyder M, Wang J, Ye K, Eichler EE, Gerstein MB, Hurles ME, Lee C, McCarroll SA, Korbel JO. Mapping copy number variation by population-scale genome sequencing. Nature. 2011 Feb 3; 470(7332):59-65. PMID: 21293372.
        View in: PubMed
      13. Radivojac P, Vacic V, Haynes C, Cocklin RR, Mohan A, Heyen JW, Goebl MG, Iakoucheva L. Identification, analysis, and prediction of protein ubiquitination sites. Proteins. 2010 Feb 1; 78(2):365-80. PMID: 19722269.
        View in: PubMed
      14. Vacic V, Iakoucheva L, Lonardi S, Radivojac P. Graphlet kernels for prediction of functional residues in protein structures. J Comput Biol. 2010 Jan; 17(1):55-72. PMID: 20078397.
        View in: PubMed
      15. Li S, Iakoucheva L, Mooney SD, Radivojac P. Loss of post-translational modification sites in disease. Pac Symp Biocomput. 2010; 337-47. PMID: 19908386.
        View in: PubMed
      16. McCarthy SE, Makarov V, Kirov G, Addington AM, McClellan J, Yoon S, Perkins DO, Dickel DE, Kusenda M, Krastoshevsky O, Krause V, Kumar RA, Grozeva D, Malhotra D, Walsh T, Zackai EH, Kaplan P, Ganesh J, Krantz ID, Spinner NB, Roccanova P, Bhandari A, Pavon K, Lakshmi B, Leotta A, Kendall J, Lee YH, Vacic V, Gary S, Iakoucheva L, Crow TJ, Christian SL, Lieberman JA, Stroup TS, Lehtimäki T, Puura K, Haldeman-Englert C, Pearl J, Goodell M, Willour VL, Derosse P, Steele J, Kassem L, Wolff J, Chitkara N, McMahon FJ, Malhotra AK, Potash JB, Schulze TG, Nöthen MM, Cichon S, Rietschel M, Leibenluft E, Kustanovich V, Lajonchere CM, Sutcliffe JS, Skuse D, Gill M, Gallagher L, Mendell NR. Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet. 2009 Nov; 41(11):1223-7. PMID: 19855392.
        View in: PubMed
      17. Uversky VN, Oldfield CJ, Midic U, Xie H, Xue B, Vucetic S, Iakoucheva L, Obradovic Z, Dunker AK. Unfoldomics of human diseases: linking protein intrinsic disorder with diseases. BMC Genomics. 2009; 10 Suppl 1:S7. PMID: 19594884.
        View in: PubMed
      18. Boxem M, Maliga Z, Klitgord N, Li N, Lemmens I, Mana M, de Lichtervelde L, Mul JD, van de Peut D, Devos M, Simonis N, Yildirim MA, Cokol M, Kao HL, de Smet AS, Wang H, Schlaitz AL, Hao T, Milstein S, Fan C, Tipsword M, Drew K, Galli M, Rhrissorrakrai K, Drechsel D, Koller D, Roth FP, Iakoucheva L, Dunker AK, Bonneau R, Gunsalus KC, Hill DE, Piano F, Tavernier J, van den Heuvel S, Hyman AA, Vidal M. A protein domain-based interactome network for C. elegans early embryogenesis. Cell. 2008 Aug 8; 134(3):534-45. PMID: 18692475.
        View in: PubMed
      19. Oldfield CJ, Meng J, Yang JY, Yang MQ, Uversky VN, Dunker AK. Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners. BMC Genomics. 2008; 9 Suppl 1:S1. PMID: 18366598.
        View in: PubMed
      20. Nikolakaki E, Drosou V, Sanidas I, Peidis P, Papamarcaki T, Iakoucheva L, Giannakouros T. RNA association or phosphorylation of the RS domain prevents aggregation of RS domain-containing proteins. Biochim Biophys Acta. 2008 Feb; 1780(2):214-25. PMID: 18022399.
        View in: PubMed
      21. Xie H, Vucetic S, Iakoucheva L, Oldfield CJ, Dunker AK, Obradovic Z, Uversky VN. Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins. J Proteome Res. 2007 May; 6(5):1917-32. PMID: 17391016.
        View in: PubMed
      22. Vucetic S, Xie H, Iakoucheva L, Oldfield CJ, Dunker AK, Obradovic Z, Uversky VN. Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions. J Proteome Res. 2007 May; 6(5):1899-916. PMID: 17391015.
        View in: PubMed
      23. Xie H, Vucetic S, Iakoucheva L, Oldfield CJ, Dunker AK, Uversky VN, Obradovic Z. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J Proteome Res. 2007 May; 6(5):1882-98. PMID: 17391014.
        View in: PubMed
      24. Uversky VN, Radivojac P, Iakoucheva L, Obradovic Z, Dunker AK. Prediction of intrinsic disorder and its use in functional proteomics. Methods Mol Biol. 2007; 408:69-92. PMID: 18314578.
        View in: PubMed
      25. Radivojac P, Iakoucheva L, Oldfield CJ, Obradovic Z, Uversky VN, Dunker AK. Intrinsic disorder and functional proteomics. Biophys J. 2007 Mar 1; 92(5):1439-56. PMID: 17158572.
        View in: PubMed
      26. Haynes C, Oldfield CJ, Ji F, Klitgord N, Cusick ME, Radivojac P, Uversky VN, Vidal M, Iakoucheva L. Intrinsic disorder is a common feature of hub proteins from four eukaryotic interactomes. PLoS Comput Biol. 2006 Aug 4; 2(8):e100. PMID: 16884331.
        View in: PubMed
      27. Vacic V, Iakoucheva L, Radivojac P. Two Sample Logo: a graphical representation of the differences between two sets of sequence alignments. Bioinformatics. 2006 Jun 15; 22(12):1536-7. PMID: 16632492.
        View in: PubMed
      28. Haynes C, Iakoucheva L. Serine/arginine-rich splicing factors belong to a class of intrinsically disordered proteins. Nucleic Acids Res. 2006; 34(1):305-12. PMID: 16407336.
        View in: PubMed
      29. Dunker AK, Cortese MS, Romero P, Iakoucheva L, Uversky VN. Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J. 2005 Oct; 272(20):5129-48. PMID: 16218947.
        View in: PubMed
      30. Bracken C, Iakoucheva L, Romero PR, Dunker AK. Combining prediction, computation and experiment for the characterization of protein disorder. Curr Opin Struct Biol. 2004 Oct; 14(5):570-6. PMID: 15465317.
        View in: PubMed
      31. Vucetic S, Obradovic Z, Vacic V, Radivojac P, Peng K, Iakoucheva L, Cortese MS, Lawson JD, Brown CJ, Sikes JG, Newton CD, Dunker AK. DisProt: a database of protein disorder. Bioinformatics. 2005 Jan 1; 21(1):137-40. PMID: 15310560.
        View in: PubMed
      32. Iakoucheva L, Radivojac P, Brown CJ, O'Connor TR, Sikes JG, Obradovic Z, Dunker AK. The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res. 2004; 32(3):1037-49. PMID: 14960716.
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      33. Iakoucheva L, Dunker AK. Order, disorder, and flexibility: prediction from protein sequence. Structure. 2003 Nov; 11(11):1316-7. PMID: 14604521.
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      34. Iakoucheva L, Brown CJ, Lawson JD, Obradovic Z, Dunker AK. Intrinsic disorder in cell-signaling and cancer-associated proteins. J Mol Biol. 2002 Oct 25; 323(3):573-84. PMID: 12381310.
        View in: PubMed
      35. Dunker AK, Brown CJ, Lawson JD, Iakoucheva L, Obradovic Z. Intrinsic disorder and protein function. Biochemistry. 2002 May 28; 41(21):6573-82. PMID: 12022860.
        View in: PubMed
      36. Iakoucheva L, Walker RK, van Houten B, Ackerman EJ. Equilibrium and stop-flow kinetic studies of fluorescently labeled DNA substrates with DNA repair proteins XPA and replication protein A. Biochemistry. 2002 Jan 8; 41(1):131-43. PMID: 11772010.
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      37. Lu HP, Iakoucheva L, Ackerman EJ. Single-molecule conformational dynamics of fluctuating noncovalent DNA-protein interactions in DNA damage recognition. J Am Chem Soc. 2001 Sep 19; 123(37):9184-5. PMID: 11552836.
        View in: PubMed
      38. Iakoucheva L, Kimzey AL, Masselon CD, Smith RD, Dunker AK, Ackerman EJ. Aberrant mobility phenomena of the DNA repair protein XPA. Protein Sci. 2001 Jul; 10(7):1353-62. PMID: 11420437.
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      39. Iakoucheva L, Kimzey AL, Masselon CD, Bruce JE, Garner EC, Brown CJ, Dunker AK, Smith RD, Ackerman EJ. Identification of intrinsic order and disorder in the DNA repair protein XPA. Protein Sci. 2001 Mar; 10(3):560-71. PMID: 11344324.
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      40. Ackerman EJ, Iakoucheva L. Nucleotide excision repair in oocyte nuclear extracts from Xenopus laevis. Methods. 2000 Oct; 22(2):188-93. PMID: 11020334.
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      41. Buchko GW, Iakoucheva L, Kennedy MA, Ackerman EJ, Hess NJ. Extended X-ray absorption fine structure evidence for a single metal binding domain in Xenopus laevis nucleotide excision repair protein XPA. Biochem Biophys Res Commun. 1999 Jan 8; 254(1):109-13. PMID: 9920741.
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