Professor Emeritus, Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University
Director, National Laboratory for the Genetics of Israeli Populations
Editorial Board Member: Trends in Molecular Medicine, Genome Medicine, CNS Drugs, Scientific Reports, Pharmacogenomics, Drug Development Research
Genomic Biomarkers for CNS Drug Response
Our lab, serving as the National Laboratory for the Genetics of Israeli Populations, was established in 1995 by the Israeli Academy for Sciences and Humanities as the National Biobank of Israel. The biobank includes DNA samples and immortalized lymphoblastoid cell lines from over 2000 unrelated healthy donors representing the large genetic diversity of Jewish, Arab and Druze communities of Israel. This novel resource has been applied by hundreds of research groups in Israel and abroad.
Our primary interest is in finding genomic biomarkers for the response to CNS drugs – , for improving personalized medicine with respect to both treatment efficacy and safety. Our research is currently focused on drugs for treating major depression, bipolar disorder, and Alzheimer’s disease. These CNS diseases inflict huge societal costs, and biomarkers are needed for better treatment. We use human immortalized lymphoblastoid cell lines from unrelated healthy donors for comparing drug response and searching for genomic biomarkers, including mRNA for genes, and non-coding RNAs such as microRNAs (miRNAs) and small nucleolar RNAs = snoRNAs.
Among genes that we identified as tentative genomic biomarkers for the response to anti-depressant drugs, two genes, CHL1 and ITGB3, have been replicated in clinical cohorts of major depression patients, lending support for our novel research approach. A recent publication from our lab has been cited in a report by Scientific American: Unraveling the Mystery of How Antidepression Drugs Work. In addition to the research on genomic biomarkers, we are involved in research on bioethics and societal aspects of human genomics research.
PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=Gurwitz+D&sort=date
Google Scholar: https://scholar.google.com/citations?user=FbxiKloAAAAJ
List of key publications updated for 2017 (use the above links for publications after 1017)
Morag A, Kirchheiner J, Rehavi M, Gurwitz D. Human lymphoblastoid cell line panels: novel tools for assessing shared drug pathways. Pharmacogenomics. 11:327-340 (2010).
Gurwitz D. Pharmacogenetics education: 10 years of experience at Tel Aviv University. Pharmacogenomics.11:647-649 (2010).
Gurwitz D, Pirmohamed M. Pharmacogenomics: the importance of accurate phenotypes. Pharmacogenomics. 11:469-470 (2010).
Bismuth-Evenzal Y, Roz N, Gurwitz D, Rehavi M. N-methyl-citalopram: A quaternary selective serotonin reuptake inhibitor. Biochem Pharmacol.
80:1546-1552 (2010).
Donnelly MP, Paschou P, Grigorenko E, Gurwitz D, Mehdi SQ, Kajuna SL, Barta C, Kungulilo S, Karoma NJ, Lu RB, Zhukova OV, Kim JJ, Comas D, Siniscalco M, New M, Li P, Li H, Manolopoulos VG, Speed WC, Rajeevan H, Pakstis AJ, Kidd JR, Kidd KK. The distribution and most recent common ancestor of the 17q21 inversion in humans. Am J Hum Genet. 86:161-171 (2010).
Shahin H, Walsh T, Rayyan AA, Lee MK, Higgins J, Dickel D, Lewis K, Thompson J, Baker C, Nord AS, Stray S, Gurwitz D, Avraham KB, King MC, Kanaan M. Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families. Eur J Hum Genet. 18:407-413 (2010).
Behar DM, Yunusbayev B, Metspalu M, Metspalu E, Rosset S, Parik J, Rootsi S, Chaubey G, Kutuev I, Yudkovsky G, Khusnutdinova EK, Balanovsky O, Semino O, Pereira L, Comas D, Gurwitz D, Bonne-Tamir B, Parfitt T, Hammer MF, Skorecki K, Villems R. The genome-wide structure of the Jewish people. Nature. 466:238-242 (2011).
Kamal SM, Warnich L, Ferguson LR, Srivastava S, Ray S, Avard D, Joly Y, Le Huynh M, Page M, Masellis M, Dove ES, Gurwitz D, Ozdemir V.Forward Look: Tenth Anniversary of the Human Genome Sequence and 21 Century Postgenomics Global Health – A Close Up on Africa and Women’s Health. Curr Pharmacogenomics Person Med. 9:148-155 (2011).
Gurwitz D, Lunshof JE. Personalized participatory medicine: sharing knowledge and uncertainty. Genome Med. 3:69 (2011).
Gurwitz D. Biomarkers: better donor protection. Nature. 470:175 (2011)
Morag M, Pasmanik-Chor M, Oron-Karni V, Rehavi M, Stingl JC, Gurwitz D. Genome-wide expression profiling of human lymphoblastoid cell lines identifies CHL1 as putative SSRI antidepressants response biomarker. Pharmacogenomics, 12:171-184 (2011).
L, Lunshof JE, Gurwitz D, Schulte In den Bäumen T, Westerhoff HV, Lange BM, Brand A. Health technology assessment in the era of personalzied health care. Int J Technol Assess Health Care. 27:118-126 (2011).
Payne K, Gurwitz D. Informing resource allocation decision making: economic evaluations of
pharmacogenetic tests. Drug Dev. Res. 71:445-448 (2011).
Oved K, Morag M, Pasmanik-Chor M, Oron-Karni V, Shomron N, Rehavi M, Stingl JC, Gurwitz D. Genomewide expression profiling of human lymphoblastoid cell lines identifies several microRNAs as tentative SSRI antidepressants response biomarkers. Pharmacogenomics 13:1129-1139 (2012).
Vincent M, Oved K, Morag A, Pasmanik-Chor M, Oron-Karni V, Shomron N, Gurwitz D. Genome-wide transcriptomic variations of human lymphoblastoid cell lines: insights from pairwise gene expression correlations. Pharmacogenomics 13:1893-904 (2012).
Bismuth-Evenzal Y, Gonopolsky Y, Gurwitz D, Iancu I, Weizman A, Rehavi M. Decreased serotonin content and reduced agonist-induced aggregation in platelets of patients chronically medicated with SSRI drugs. J Affect Disord. 136:99-103 (2012).
Donnelly MP, Paschou P, Grigorenko E, Gurwitz D, Barta C, Lu RB, Zhukova OV, Kim JJ, Siniscalco M, New M, Li H, Kajuna SL, Manolopoulos VG, Speed WC, Pakstis AJ, Kidd JR, Kidd KK. A global view of the OCA2-HERC2 region and pigmentation. Hum Genet. 131:683-696 (2012).
Lunshof JE, Gurwitz D. Pharmacogenomic testing: knowing more, doing better. Clin Pharmacol Ther. 91:387-389 (2012).
van Mulligen EM, Fourrier-Reglat A, Gurwitz D, Molokhia M, Nieto A, Trifiro G, Kors JA, Furlong LI. The EU -ADR corpus: Annotated drugs, diseases, targets, and their relationships. J Biomed Inform. 45:879-884 (2012).
Tomková M, Marohnic CC, Gurwitz D, Seda O, Masters BS, Martásek P. Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations. Pharmacogenomics. 13:543-554 (2012).
Gurwitz D. High-Quality Phenomics are Crucial for Informative Omics Studies. Drug Development Research 73:353-356 (2012).
Gurwitz D. Data re-identification: protect the children. Science. 339(6123):1033 (2013).
Lunshof JE, Gurwitz D. Parental consent: Guarding children’s genetic privacy. Nature. 494:430 (2013).
Morag A, Oved K, Gurwitz D. Sex differences in human lymphoblastoid cells sensitivities to antipsychotic drugs. J Mol Neurosci. 49:554-8 (2013).
Gurwitz D, McLeod HL. Genome-wide studies in pharmacogenomics: harnessing the power of
extreme phenotypes. Pharmacogenomics. 14:337- 339 (2013).
Gurwitz D. Expression profiling: a cost-effective biomarker discovery tool for the personal genome
era. Genome Med. 5:41 (2013).
Oved K, Morag A, Pasmanik-Chor M, Rehavi M, Shomron N, Gurwitz D. Genome-wide expression profiling of human lymphoblastoid cell lines implicates integrin beta-3 in the mode of action of antidepressants. Transl Psychiatry. 3:e313 (2013).
Verhoef TI, Ragia G, de Boer A, Barallon R, Kolovou G, Kolovou V, Konstantinides S, Le Cessie S, Maltezos E, van der Meer FJ, Redekop WK, Remkes M, Rosendaal FR, van Schie RM, Tavridou A, Tziakas D, Wadelius M, Manolopoulos VG, Maitland-van der Zee AH; EU-PACT Group. A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. N Engl J Med. 369:2304-12 (2013).
Gurwitz D. Gene drives raise dual-use concerns. Science. 345:1010 (2014).
Gurwitz D. Computing: Keep files small to curb energy use. Nature. 514:305 (2014).
Gurwitz D. From transcriptomics to biological networks. Drug Dev Res. 75(5):267-70 (2014).
Gurwitz D., Milanesi E, Koenig T. Grant application review: the case of transparency. PLoS Biology. DOI:
10.1371/journal.pbio.1002010 (2014).
Chouchana L, Fernández-Ramos AA, Dumont F, Marchetti C, Ceballos-Picot I, Beaune P, Gurwitz D, Loriot MA. Molecular insight into thiopurine resistance: transcriptomic signature in lymphoblastoid cell lines. Genome Med. 7:37 (2015).
Markovič T, Gobec M, Gurwitz D, Mlinarič-Raščan I. Characterization of human lymphoblastoid cell lines as a novel in vitro test system to predict the immunotoxicity of xenobiotics. Toxicol Lett. 233:8-15 (2015).
Milanesi E, Hadar A, Maffioletti E, Werner H, Shomron N, Gennarelli M, Schulze TG, Costa M, Del Zompo M, Squassina A, Gurwitz D. Insulin-like Growth Factor 1 Differentially Affects Lithium Sensitivity of Lymphoblastoid Cell Lines from Lithium Responder and Non-responder Bipolar Disorder Patients. J Mol Neurosci. 56:681-7 (2015).
Fabbri C, Crisafulli C, Gurwitz D, Stingl J, Calati R, Albani D, Forloni G, Calabrò M, Martines R, Kasper S, Zohar J, Juven-Wetzler A, Souery D, Montgomery S, Mendlewicz J, Girolamo GD, Serretti A. Neuronal cell adhesion genes and antidepressant response in three independent samples. Pharmacogenomics J. 15:538-48 (2015).
Probst-Schendzielorz K, Scholl C, Efimkina O, Ersfeld E, Viviani R, Serretti A, Fabbri C, Gurwitz D, Lucae S, Ising M, Paul AM, Lehmann ML, Steffens M, Crisafulli C, Calabrò M, Holsboer F, Stingl J. CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: results from the Munich Antidepressant Response Signature (MARS) study. Pharmacogenomics. 16:689-701 (2015).
Lapkina-Gendler L, Rotem I, Pasmanik-Chor M, Gurwitz D, Sarfstein R, Laron Z, Werner H. Identification of signaling pathways associated with cancer protection in Laron syndrome. Endocr Relat Cancer. 23:399-410 (2016).
Rzezniczek S, Obuchowicz M, Datka W, Siwek M, Dudek D, Kmiotek K, Oved K, Shomron N, Gurwitz D, Pilc A. Decreased sensitivity to paroxetine-induced inhibition of peripheral blood mononuclear cell growth in depressed and antidepressant treatment-resistant patients. Transl Psychiatry. 6:e827 (2016).
Hadar A, Milanesi E, Squassina A, Niola P, Chillotti C, Pasmanik-Chor M, Yaron O, Martásek P, Rehavi M, Weisglass-Volkov D, Shomron N, Gozes I, Gurwitz D. RGS2 expression predicts amyloid-β sensitivity, MCI and Alzheimer’s disease: genome wide transcriptomic profiling and bioinformatics data mining. Transl Psychiatry ;6(10):e909. doi: 10.1038/tp.2016.179.
Reviews
Gurwitz D. Genetic privacy: trust is not enough. Science. 347:957-8 (2015).
Gurwitz D. Exosomal microRNAs in tissue crosstalk. Drug Dev Res. 76:259-62 (2015).
Gurwitz D. Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders. Dialogues Clin Neurosci. 2016 Sep;18(3):267-276.
