Oscar M. Harari, PhD

Associate Professor

Computational and Systems Biology Program
Human and Statistical Genetics Program
Biomedical Informatics and Data Science Program

  • (314) 273-1862

  • BJCIH, Room 9615

  • harario@wustl.edu

  • Neurodegeneration, Alzheimer`s Disease, Genetics, Transcriptomics, Proteomics, Bioinformatics, Next generation sequencing

  • Identification of "omics" (proteomic, transcriptomic and genetic) factors associated with neurodegeneration

Research Abstract:

My research interests are focused on the interrogation of rich phenotypic, genomic, transcriptomic and proteomic dataset of neurodegenerative diseases to identify profiles that provide novel insight into altered pathways associated with disease etiology and progression.

I believe that aggregating distinct omics datasets will increase the chances of understanding the genetic architecture of complex neurodegenerative diseases. My research is based on applying and developing methods that combine high dimensional publicly available GWAS, exome-chip, whole-genome, and exome sequencing, methylation, RNA-seq, quantitative protein and clinical longitudinal data to identify associations otherwise missed in traditional genetic analysis. Distinct bioinformatic approaches that aggregate data from multiple sources (for example, genomic, transcriptomic and epigenetic) have been successfully applied to study other diseases, revealing associations otherwise missed when analyzing each of this "omic" data by themselves.

Genetic studies findings are most of the times difficult to interpret and their functional impact often lack of identification. By using and aggregating intermediate traits additional biological insight can be gained; as is the case of the analysis of surrogate tissues (i.e. cerebrospinal fluid (CSF) to study the brain proteome); brain from biopsies (i.e. gene expression and epigenetic factors) and Induced pluripotent stem cell derived neurons for functional studies. All of these alternatives limit the number of samples available to analyze. However, the research community has invested a huge amount of effort to collect a rich set of phenotypic variables that describe
the distinct aspects and progression of neurological diseases; which opens the opportunity to interrogate the data in integrative approaches. Thus, I believe that genetic studies can be interrogated using these novel approaches to provide answers to specific hypothesis.

Selected Publications:

Polygenic risk score of sporadic late-onset Alzheimer`s disease reveals a shared architecture with the familial and early-onset forms. Cruchaga C, Del-Aguila JL, Saef B, Black K, Fernandez MV, Budde J, Ibanez L, Deming Y, Kapoor M, Tosto G, Mayeux RP, Holtzman DM, Fagan AM, Morris JC, Bateman RJ, Goate AM, Harari O. Alzheimer`s & dementia : the journal of the Alzheimer`s Association. 2017;

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. Fernández MV, Kim JH, Budde JP, Black K, Medvedeva A, Saef B, Deming Y, Del-Aguila J, Ibañez L, Dube U, Harari O, Norton J, Chasse R, Morris JC, Goate A, Cruchaga C. PLoS genetics. 2017; 13(11):e1007045.

Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels. Ibanez L, Dube U, Saef B, Budde J, Black K, Medvedeva A, Del-Aguila JL, Davis AA, Perlmutter JS, Harari O, Benitez BA, Cruchaga C. BMC neurology. 2017; 17(1):198.

CSF protein changes associated with hippocampal sclerosis risk gene variants highlight impact of GRN/PGRN.
Fardo DW, Katsumata Y, Kauwe JS, Deming Y, Harari O, Cruchaga C, Nelson PT. Experimental gerontology. 2017; 90:83-89. NIHMSID: NIHMS852700

Genome-wide association study identifies four novel loci associated with Alzheimer`s endophenotypes and disease modifiers. Deming Y, Li Z, Kapoor M, Harari O, Del-Aguila JL, Black K, Carrell D, Cai Y, Fernandez MV, Budde J, Ma S, Saef B, Howells B, Huang KL, Bertelsen S, Fagan AM, Holtzman DM, Morris JC, Kim S, Saykin AJ, De Jager PL, Albert M, Moghekar A, O`Brien R, Riemenschneider M, Petersen RC, Blennow K, Zetterberg H, Minthon L, Van Deerlin VM, Lee VM, Shaw LM, Trojanowski JQ, Schellenberg G, Haines JL, Mayeux R, Pericak-Vance MA, Farrer LA, Peskind ER, Li G, Di Narzo AF, Kauwe JS, Goate AM, Cruchaga C. Acta neuropathologica. 2017; 133(5):839-856. NIHMSID: NIHMS902770

A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer`s disease. Huang KL, Marcora E, Pimenova AA, Di Narzo AF, Kapoor M, Jin SC, Harari O, Bertelsen S, Fairfax BP, Czajkowski J, Chouraki V, Grenier-Boley B, Bellenguez C, Deming Y, McKenzie A, Raj T, Renton AE, Budde J, Smith A, Fitzpatrick A, Bis JC, DeStefano A, Adams HHH, Ikram MA, van der Lee S, Del-Aguila JL, Fernandez MV, Ibañez L, Sims R, Escott-Price V, Mayeux R, Haines JL, Farrer LA, Pericak-Vance MA, Lambert JC, van Duijn C, Launer L, Seshadri S, Williams J, Amouyel P, Schellenberg GD, Zhang B, Borecki I, Kauwe JSK, Cruchaga C, Hao K, Goate AM. Nature neuroscience. 2017; 20(8):1052-1061.

Last Updated: 1/23/2018 9:25:56 AM

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