Lilia M. Iakoucheva, PhD
Department of Psychiatry
University of California, San Diego
9500 Gilman Drive, MC 0603
La Jolla, CA 92093-0603
Dr. Lilia Iakoucheva received her PhD degree from the Institute of Immunology, Moscow, Russia. After completing postdoctoral training in protein biochemistry and protein structure/intrinsic disorder analysis, she joined The Rockefeller University (New York, NY) as a Research Assistant Professor, and then the faculty of the UCSD Department of Psychiatry as an Assistant Professor. Dr. Iakoucheva is applying her experience in protein structure and protein-protein interactions analysis towards investigation of psychiatric disorders. Her research focuses on understanding molecular basis of psychiatric diseases using systems biology approaches. Dr. Iakoucheva has been the principal investigator on research grants from NSF, NCI, NICHD, and NIMH.
Genes play an important role in the etiology of psychiatric disorders. Recent genome-wide association (GWA) studies and studies of copy number variants (CNVs) and single nucleotide polymorphisms (SNPs) in psychiatric diseases implicated a large number of different genes including common and rare variants. Our main goal is to understand how these seemingly unrelated candidate genes contribute to psychiatric diseases, such as autism and schizophrenia.
Like their normal counterparts, protein products of disease genes do not function in isolation, but are part of highly interconnected cellular networks. Given potentially large number of genes involved, and the complexity of the interactions of their protein products, the “one-gene/protein-at-a-time” approaches to study psychiatric diseases may be too slow and labor-intensive. As an alternative to the “one-gene/protein-at-a-time” approach, we propose to look at psychiatric disorders from so-called “systems biology” perspective. We hypothesize that defects in multiple genes that are diverse in their individual functions, but interact within the context of common cellular pathways/networks/functional modules are important for disease pathogenesis.
To discover these common pathways/networks of psychiatric diseases, we are building disease-focused protein-protein interaction networks (i.e. disease interactomes) using experimental (yeast two-hybrid) and computational (“omics”) approaches. Our goals are: (1) to construct comprehensive maps of protein-protein interaction networks for autism and schizophrenia candidate genes; (2) to define the splicing repertoire of the autism and schizophrenia candidate genes; (3) to integrate the splicing interactomes with the traditional interactomes of autism and schizophrenia candidate proteins; (4) to investigate the perturbations of the disease networks and functional modules by CNV mutations identified from the patients. We believe that the “pathway” hypothesis could explain how defects in seemingly unrelated genes contribute to psychiatric disease pathogenesis, and how the defects in the same gene lead to the diversity of psychiatric disease manifestations.
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