Lilia M. Iakoucheva, Ph.D. 

Assistant Professor

Iakoucheva Lab

 

Contact Information

9500 Gilman Drive, MC 0603
La Jolla, CA 92093-0603
T: (858) 822-1878
F: (858) 534-7653
lilyak@ucsd.edu

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

Research Focus

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.

Publications

  • Uversky VN, Davé V, Iakoucheva LM, Malaney P, Metallo SJ, Pathak RR, Joerger AC. Pathological Unfoldomics of Uncontrolled Chaos: Intrinsically Disordered Proteins and Human Diseases. Chem Rev. 2014 May 15. PMID: 24830552
  • 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 LM. Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. Nat. Commun. 2014 April 11;5:3650 doi: 10.1038/ncomms4650. PMID: 24722188. (* Equal contribution) (Featured by SFARI, UCSD, Nature Commu, ScienceDaily, neurosciencenews, newswise, bioon)
  • Dembinski H, Wismer K, Balasubramaniam D, Gonzalez HA, Alverdi V, Iakoucheva LM, Komives EA. Predicted disorder-to-order transition mutations in IκBα disrupt function. Phys Chem Chem Phys. 2014 Apr 14;16(14):6480-5. doi: 10.1039/c3cp54427c. Epub 2014 Mar 6. PMID: 2460536
  • 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 LM, 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
  • Vacic V, Markwick P, Oldfield CJ, Zhao X, Haynes C, Uversky V, Iakoucheva LM. Disease-associated mutations disrupt functionally important regions of intrinsic protein disorder. PLoS Comput Biol. 2012 Oct, 9 (11). PMID: 23055912
  • Vacic V, Iakoucheva LM. Disease mutations in disordered regions--exception to the rule? Mol. BioSyst. 2011 Nov 8, 27-32. PMID: 22080206
  • Vacic V, … Corominas R, Iakoucheva LM...[30 authors], Sebat J. Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature. 2011 Feb;471(7339):499-503. PMID: 21346763
  • Mills R, … Iakoucheva LM…[57 authors], Korbel J. Mapping copy number variation by population-scale genome sequencing Nature. 2011 Nov;470(7332):59-65. PMID: 21293372
  • Radivojac P, Vacic V, Haynes C, Cocklin RR, Mohan A, Heyen JW, Goebl MG, Iakoucheva LM. Identification, analysis, and prediction of protein ubiquitination sites. Proteins. 2010 Feb 1;78(2):365-80. PMID: 19722269
  • Vacic V, Iakoucheva LM, 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
  • Li S, Iakoucheva LM, Mooney SD, Radivojac P. Loss of post-translational modification sites in disease. Pac Symp Biocomput. 2010:337-47. PMID: 19908386
  • McCarthy SE, … Iakoucheva LM…[71 authors], Sebat J. Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet. 2009 Nov;41(11):1223-7. PMID: 19855392
  • Boxem M, … Iakoucheva LM… [36 authors], Vidal M. A protein domain-based interactome network for C. elegans early embryogenesis. Cell. 2008 Aug 8;134(3):534-45. PMID: 18692475
  • Haynes C, Oldfield CJ, Ji F, Klitgord N, Cusick ME, Radivojac P, Uversky VN, Vidal M, Iakoucheva LM. Intrinsic disorder is a common feature of hub proteins from four eukaryotic interactomes. PLoS Comput Biol. 2006 Aug 4;2(8):e100. Epub 2006 Jun 23. PMID: 16884331
  • Haynes C, Iakoucheva LM. Serine/arginine-rich splicing factors belong to a class of intrinsically disordered proteins. Nucleic Acids Res. 2006 Jan 10;34(1):305-12. PMID: 16407336
  • Iakoucheva LM, 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 Feb 11;32(3):1037-49. PMID: 14960716
  • Iakoucheva LM, Brown CJ, Lawson JD, Obradović Z, Dunker AK. Intrinsic disorder in cell-signaling and cancer-associated proteins. J Mol Biol. 2002 Oct 25;323(3):573-84. PMID: 12381310
  • Dunker AK, Brown CJ, Lawson JD, Iakoucheva LM, Obradović Z. Intrinsic disorder and protein function. Biochemistry. 2002 May 28;41(21):6573-82. PMID: 12022860