Sagiv Shifman

Sagiv Shifman (born August 2, 1971) is an Israeli scientist, professor in the field of neurogenetics at the Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem. He holds the Arnold and Bess Zeldich Ungerman chair in Neurobiology.

Sagiv Shifman
BornAugust 2, 1971
NationalityIsraeli
Alma materThe Hebrew University of Jerusalem
Scientific career
InstitutionsThe Hebrew University of Jerusalem
Websitehttps://neurogenetics.huji.ac.il/

Biography

Sagiv Shifman was born in Jerusalem in 1971 to Rachel and Pinhas Shifman. He completed all his degrees at The Hebrew University of Jerusalem. His doctorate was under the guidance of Ariel Darvasi in the genetics of complex traits, focusing on the genetic mapping of schizophrenia.[1] In 2004 he started post-doctoral studies at the University of Oxford, in Jonathan Flint's laboratory, where he worked on genetic mapping in mice[2] and genetics of neuroticism in humans.[3] In 2008 he returned to Israel and founded the Neurogenetics Research Laboratory at the Department of Genetics, the Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem. In 2015 he was a visiting professor at the University of California at Los Angeles (UCLA) for about a year.

In 2013, he won the Krill Prize[4] from the Wolf Foundation for excellence in scientific research.

Between 2017 and 2021, he served as the head of the genetics teaching program at the Hebrew University, and then as the head of the department.

Sagiv is married to Limor Shifman, father of two, and lives in Jerusalem.

Research

Shifman's main research area is the genetics of neurodevelopmental and psychiatric disorders. His research focuses on genetic, molecular, and neurobiological mechanisms that lead to these disorders. His laboratory studies genetic variations in the human genome that affect gene function or regulation and investigates the relationship between genomics and neurodevelopmental disorders, focusing mainly on autism spectrum disorders.

His studies span over several fields and can be divided into three main topics:

• Genetic mapping of psychiatric diseases - Shifman's early works dealt with creating genetic maps in humans and mice and identifying genes related to schizophrenia and neuroticism.[1][2][3][5][6][7]

• Biological mechanisms related to the autism spectrum - Shifman's laboratory pioneered the development of approaches to studying genes related to autism through the analysis of gene networks and their expression pattern in the human brain. Using these methods, they were able to show for the first time that genes related to autism are involved in the control of transcription, many of them are chromatin regulators, and that these genes are active during early brain development.[8][9][10] In a series of articles, they studied the mechanism of autism-related chromatin regulators using a cellular, mouse, and fly models.[11][12][13]

• Essential genes in mice and humans - to study genes sensitive to mutations, Shifman's laboratory conducted a CRISPR genetic screen for essential genes in mouse embryonic stem cells.[14] In this study, they report the most comprehensive and systematic analysis of essential genes in the mouse genome, greatly expanding the understanding of essential genes for embryonic stem cells. This work shows that many of the genes associated with neurodevelopmental disorders are already essential at very early embryonic stages. In other studies, they identify the mechanisms that cause genes to be essential in human cancer cells originating from specific tissues.[15] They also identify genes that are affected by the sex chromosomes and show differences in essentiality between males and females.[16]

References
  1. Shifman, Sagiv; Bronstein, Michal; Sternfeld, Meira; Pisanté-Shalom, Anne; Lev-Lehman, Efrat; Weizman, Avraham; Reznik, Ilya; Spivak, Baruch; Grisaru, Nimrod; Karp, Leon; Schiffer, Richard; Kotler, Moshe; Strous, Rael D.; Swartz-Vanetik, Marnina; Knobler, Haim Y. (December 2002). "A Highly Significant Association between a COMT Haplotype and Schizophrenia". The American Journal of Human Genetics. 71 (6): 1296–1302. doi:10.1086/344514. PMC 378567. PMID 12402217.
  2. Shifman, Sagiv; Bell, Jordana Tzenova; Copley, Richard R.; Taylor, Martin S.; Williams, Robert W.; Mott, Richard; Flint, Jonathan (November 2006). "A high-resolution single nucleotide polymorphism genetic map of the mouse genome". PLOS Biology. 4 (12): e395. doi:10.1371/journal.pbio.0040395. ISSN 1545-7885. PMC 1635748. PMID 17105354.
  3. Shifman, S; Bhomra, A; Smiley, S; Wray, N R; James, M R; Martin, N G; Hettema, J M; An, S S; Neale, M C; van den Oord, E J C G; Kendler, K S; Chen, X; Boomsma, D I; Middeldorp, C M; Hottenga, J J (March 2008). "A whole genome association study of neuroticism using DNA pooling". Molecular Psychiatry. 13 (3): 302–312. doi:10.1038/sj.mp.4002048. ISSN 1359-4184. PMC 4004964. PMID 17667963.
  4. "The Krill Prize, Wolf Foundation".
  5. Shifman, Sagiv; Darvasi, Ariel (August 2001). "The value of isolated populations". Nature Genetics. 28 (4): 309–310. doi:10.1038/91060. ISSN 1061-4036. PMID 11479587. S2CID 20913559.
  6. Shifman, Sagiv; Kuypers, Jane; Kokoris, Mark; Yakir, Benjamin; Darvasi, Ariel (2003-04-01). "Linkage disequilibrium patterns of the human genome across populations". Human Molecular Genetics. 12 (7): 771–776. doi:10.1093/hmg/ddg088. ISSN 0964-6906. PMID 12651872.
  7. Shifman, Sagiv; Johannesson, Martina; Bronstein, Michal; Chen, Sam X; Collier, David A; Craddock, Nicholas J; Kendler, Kenneth S; Li, Tao; O'Donovan, Michael; O'Neill, F. Anthony; Owen, Michael J; Walsh, Dermot; Weinberger, Daniel R; Sun, Cuie; Flint, Jonathan (2008-02-15). Gibson, Greg (ed.). "Genome-Wide Association Identifies a Common Variant in the Reelin Gene That Increases the Risk of Schizophrenia Only in Women". PLOS Genetics. 4 (2): e28. doi:10.1371/journal.pgen.0040028. ISSN 1553-7404. PMC 2242812. PMID 18282107.
  8. Ben-David, Eyal; Shifman, Sagiv (2012-03-08). Gibson, Greg (ed.). "Networks of Neuronal Genes Affected by Common and Rare Variants in Autism Spectrum Disorders". PLOS Genetics. 8 (3): e1002556. doi:10.1371/journal.pgen.1002556. ISSN 1553-7404. PMC 3297570. PMID 22412387.
  9. Ben-David, E; Shifman, S (October 2013). "Combined analysis of exome sequencing points toward a major role for transcription regulation during brain development in autism". Molecular Psychiatry. 18 (10): 1054–1056. doi:10.1038/mp.2012.148. ISSN 1359-4184. PMID 23147383. S2CID 3002086.
  10. Shohat, Shahar; Ben-David, Eyal; Shifman, Sagiv (2017-02-28). "Varying Intolerance of Gene Pathways to Mutational Classes Explain Genetic Convergence across Neuropsychiatric Disorders". Cell Reports. 18 (9): 2217–2227. doi:10.1016/j.celrep.2017.02.007. ISSN 2211-1247. PMID 28249166.
  11. Monderer-Rothkoff, Galya; Tal, Nitzan; Risman, Marina; Shani, Odem; Nissim-Rafinia, Malka; Malki-Feldman, Laura; Medvedeva, Vera; Groszer, Matthias; Meshorer, Eran; Shifman, Sagiv (February 2021). "AUTS2 isoforms control neuronal differentiation". Molecular Psychiatry. 26 (2): 666–681. doi:10.1038/s41380-019-0409-1. ISSN 1476-5578. PMID 30953002. S2CID 96448731.
  12. Suliman-Lavie, Reut; Title, Ben; Cohen, Yahel; Hamada, Nanako; Tal, Maayan; Tal, Nitzan; Monderer-Rothkoff, Galya; Gudmundsdottir, Bjorg; Gudmundsson, Kristbjorn O.; Keller, Jonathan R.; Huang, Guo-Jen; Nagata, Koh-Ichi; Yarom, Yosef; Shifman, Sagiv (2020-11-17). "Pogz deficiency leads to transcription dysregulation and impaired cerebellar activity underlying autism-like behavior in mice". Nature Communications. 11 (1): 5836. Bibcode:2020NatCo..11.5836S. doi:10.1038/s41467-020-19577-0. ISSN 2041-1723. PMC 7673123. PMID 33203851.
  13. Herman, Neta; Kadener, Sebastian; Shifman, Sagiv (2022-12-06). "The chromatin factor ROW cooperates with BEAF ‐32 in regulating long‐range inducible genes". EMBO Reports. 23 (12): e54720. doi:10.15252/embr.202254720. ISSN 1469-221X. PMC 9724677. PMID 36245419.
  14. Shohat, Shahar; Shifman, Sagiv (November 2019). "Genes essential for embryonic stem cells are associated with neurodevelopmental disorders". Genome Research. 29 (11): 1910–1918. doi:10.1101/gr.250019.119. ISSN 1549-5469. PMC 6836742. PMID 31649057.
  15. Dvir, Elad; Shohat, Shahar; Flint, Jonathan; Shifman, Sagiv (2022-11-01). "Identification of genetic mechanisms for tissue-specific genetic effects based on CRISPR screens". Genetics. 222 (3): iyac134. doi:10.1093/genetics/iyac134. ISSN 1943-2631. PMC 9630981. PMID 36063051.
  16. Shohat, Shahar; Vol, Ethel; Shifman, Sagiv (2022-11-23). "Gene essentiality in cancer cell lines is modified by the sex chromosomes". Genome Research. 32 (11–12): 1993–2002. doi:10.1101/gr.276488.121. ISSN 1549-5469. PMC 9808629. PMID 36418059.
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