2024 research activities

Head Prof. Yitzhak Pilpel

Picture of Prof. Yitzhak Pilpel
Head

Prof. Yitzhak Pilpel

Office +972-8-934-6058

Overview

The molecular basis of genetics and related biological processes are under investigation in our Department. The investigators approach these processes from the most reduced and reconstructed systems up to more systemic and computational analysis. Different organisms are employed including virus, yeast, Drosophila, mouse and human. These animal models and cell culture systems are used to study the mechanisms of;
a. Basic processes in gene expression, such as transcription, translation and protein degradation.
b. Cellular responses to various stimuli, such as cytokines, growth factors and exposure to DNA-damage.
c. Regulation of cell growth, senescence, differentiation and death.
d. Development; Mechanistic view of zygote to embryo transition and development of various organs, such as brain, muscles, bones and pancreas.
e. Genetic and acquired diseases such as cancer and virus infection. Embryonic stem cell biology, early development and advance human disease modeling.
f. Study of pluripotent stem cell biology and epigenetic reprogramming.
g. Computational and system biology. The function/evolution of genes and their diversification.

ScientistsShow details

  • Picture of Dr. Yaron Antebi

    Dr. Yaron Antebi

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    Developing a systems-level framework to characterize signal integration at the single cell level.
    Defining the role of perception and integration of complex stimuli in determining cellular fate.
    Analyzing multi-ligand information processing in the BMP/TGFβ pathway and its effect on mesenchymal stem cell differentiation.
    Studying signal processing capabilities of additional pathways (e.g. JAK/STAT, Wnt, FGF)

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  • Picture of Prof. Eli Arama

    Prof. Eli Arama

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    Cell death related mechanisms in Drosophila development
    Caspase-dependent non-lethal cellular processes
    Caspase-independent alternative cell death programs in Development
    Formation of the sperm mitochondria and its elimination after fertilization in Drosophila

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  • Picture of Prof. Ari Elson

    Prof. Ari Elson

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    Development and activity of bone-resorbing osteoclasts in health and disease
    Osteoclasts
    Osteoclast-related diseases: osteoporosis, osteopetrosis, cancer-related bone loss
    cell fusion
    cytoskeleton

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  • Picture of Prof. Jeffrey Gerst

    Prof. Jeffrey Gerst

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    Intracellular and Intercellular mRNA trafficking
    Collaboration with:  Prof. Robert Singer (Albert Einstein College of Medicine) Prof. Markus Landthaler (Max Delbruck Center for Molecule Medicine) Prof. Andre Levchenko (Yale University) Prof. Yitzhak Pilpel (Weizmann Institute of Science)
    Intracellular mRNA trafficking in yeast and its role in organelle biogenesis and cell physiology
    Intercellular trafficking of mRNAs in mammalian cells and its role in cell physiology
    Genome-wide mapping of mRNA localization in yeast
    Specialized ribosomes in the control of protein translation
    Identification of genes involved in chemotropism and chemotaxis

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  • Picture of Dr. David Gokhman

    Dr. David Gokhman

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    Human evolution and gene regulation
    What are the genetic changes that made us human? What is the origin of human-specific diseases? How can we computationally infer traits from genetic data? ?What is the genetic basis of human adaptation

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  • Picture of Prof. Yoram Groner

    Prof. Yoram Groner

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    Runx transcription factor 1 and 3 in development and disase
    Collaboration with:  The Proprioceptive System Masterminds Spinal Alignment: Insight into the Mechanism of Scoliosis. Blecher R, Krief S, Galili T, Biton IE, Stern T, Assaraf E, Levanon D, Appel E, Anekstein Y, Agar G, Groner Y, Zelzer E. Dev Cell. 2017 Aug 21;42(4):388-399.e3. doi: 10.1016/j.devcel.2017.07.022. PMID: 28829946 Similar articles Select item 28621410 2. The Leo Sachs' legacy: a pioneer's journey through hematopoiesis. Lotem J, Groner Y. Int J Dev Biol. 2017;61(3-4-5):127-136. doi: 10.1387/ijdb.160262yg. PMID: 28621410 Similar articles Select item 28299669 3. Runx3 in Immunity, Inflammation and Cancer. Lotem J, Levanon D, Negreanu V, Bauer O, Hantisteanu S, Dicken J, Groner Y. Adv Exp Med Biol. 2017;962:369-393. doi: 10.1007/978-981-10-3233-2_23. Review. PMID: 28299669 Similar articles Select item 28007784 4. An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons. Appel E, Weissmann S, Salzberg Y, Orlovsky K, Negreanu V, Tsoory M, Raanan C, Feldmesser E, Bernstein Y, Wolstein O, Levanon D, Groner Y. Genes Dev. 2016 Dec 1;30(23):2607-2622. doi: 10.1101/gad.291484.116. PMID: 28007784 Free PMC Article Similar articles Select item 26697350 5. Genomic-wide transcriptional profiling in primary myoblasts reveals Runx1-regulated genes in muscle regeneration. Umansky KB, Feldmesser E, Groner Y. Genom Data. 2015 Sep 1;6:120-2. doi: 10.1016/j.gdata.2015.08.030. eCollection 2015 Dec. PMID: 26697350 Free PMC Article Similar articles Select item 26414766 6. Runx3 specifies lineage commitment of innate lymphoid cells. Ebihara T, Song C, Ryu SH, Plougastel-Douglas B, Yang L, Levanon D, Groner Y, Bern MD, Stappenbeck TS, Colonna M, Egawa T, Yokoyama WM. Nat Immunol. 2015 Nov;16(11):1124-33. doi: 10.1038/ni.3272. Epub 2015 Sep 28. PMID: 26414766 Free PMC Article Similar articles Select item 26275053 7. Runx1 Transcription Factor Is Required for Myoblasts Proliferation during Muscle Regeneration. Umansky KB, Gruenbaum-Cohen Y, Tsoory M, Feldmesser E, Goldenberg D, Brenner O, Groner Y. PLoS Genet. 2015 Aug 14;11(8):e1005457. doi: 10.1371/journal.pgen.1005457. eCollection 2015 Aug. PMID: 26275053 Free PMC Article Similar articles Select item 25641675 8. Runx3 at the interface of immunity, inflammation and cancer. Lotem J, Levanon D, Negreanu V, Bauer O, Hantisteanu S, Dicken J, Groner Y. Biochim Biophys Acta. 2015 Apr;1855(2):131-43. doi: 10.1016/j.bbcan.2015.01.004. Epub 2015 Jan 30. Review. PMID: 25641675 Free Article Similar articles Select item 25605327 9. Loss of osteoblast Runx3 produces severe congenital osteopenia. Bauer O, Sharir A, Kimura A, Hantisteanu S, Takeda S, Groner Y. Mol Cell Biol. 2015 Apr;35(7):1097-109. doi: 10.1128/MCB.01106-14. Epub 2015 Jan 20. PMID: 25605327 Free PMC Article 10. Carcinogen-induced skin tumor development requires leukocytic expression of the transcription factor Runx3. Bauer O, Hantisteanu S, Lotem J, Groner Y. Cancer Prev Res (Phila). 2014 Sep;7(9):913-26. doi: 10.1158/1940-6207.CAPR-14-0098-T. Epub 2014 Jun 24. PMID: 24961879 Free Article Similar articles Select item 24469826 11. Pioneer of hematopoietic colony-stimulating factors: Leo Sachs (1924-2013). Sela M, Groner Y. Proc Natl Acad Sci U S A. 2014 Feb 4;111(5):1664-5. doi: 10.1073/pnas.1324228111. Epub 2014 Jan 27. No abstract available. PMID: 24469826 Free PMC Article Similar articles Select item 24421391 12. Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation. Levanon D, Negreanu V, Lotem J, Bone KR, Brenner O, Leshkowitz D, Groner Y. Mol Cell Biol. 2014 Mar;34(6):1158-69. doi: 10.1128/MCB.01202-13. Epub 2014 Jan 13. PMID: 24421391 Free PMC Article Similar articles Select item 24236182 13. Runx3-mediated transcriptional program in cytotoxic lymphocytes. Lotem J, Levanon D, Negreanu V, Leshkowitz D, Friedlander G, Groner Y. PLoS One. 2013 Nov 13;8(11):e80467. doi: 10.1371/journal.pone.0080467. eCollection 2013. PMID: 24236182 Free PMC Article Similar articles Select item 24204843 14. Transcriptional reprogramming of CD11b+Esam(hi) dendritic cell identity and function by loss of Runx3. Dicken J, Mildner A, Leshkowitz D, Touw IP, Hantisteanu S, Jung S, Groner Y. PLoS One. 2013 Oct 15;8(10):e77490. doi: 10.1371/journal.pone.0077490. eCollection 2013. PMID: 24204843 Free PMC Article Similar articles Select item 24055056 15. Addiction of t(8;21) and inv(16) acute myeloid leukemia to native RUNX1. Ben-Ami O, Friedman D, Leshkowitz D, Goldenberg D, Orlovsky K, Pencovich N, Lotem J, Tanay A, Groner Y. Cell Rep. 2013 Sep 26;4(6):1131-43. doi: 10.1016/j.celrep.2013.08.020. Epub 2013 Sep 19. PMID: 24055056 Free Article Similar articles Select item 23717578 16. Cell-autonomous function of Runx1 transcriptionally regulates mouse megakaryocytic maturation. Pencovich N, Jaschek R, Dicken J, Amit A, Lotem J, Tanay A, Groner Y. PLoS One. 2013 May 23;8(5):e64248. doi: 10.1371/journal.pone.0064248. Print 2013. PMID: 23717578 Free PMC Article Similar articles Select item 22903063 17. Positional differences of axon growth rates between sensory neurons encoded by Runx3. Lallemend F, Sterzenbach U, Hadjab-Lallemend S, Aquino JB, Castelo-Branco G, Sinha I, Villaescusa JC, Levanon D, Wang Y, Franck MC, Kharchenko O, Adameyko I, Linnarsson S, Groner Y, Turner E, Ernfors P. EMBO J. 2012 Sep 12;31(18):3718-29. doi: 10.1038/emboj.2012.228. Epub 2012 Aug 17. PMID: 22903063 Free PMC Article Similar articles Select item 22693452 18. The App-Runx1 region is critical for birth defects and electrocardiographic dysfunctions observed in a Down syndrome mouse model. Raveau M, Lignon JM, Nalesso V, Duchon A, Groner Y, Sharp AJ, Dembele D, Brault V, Hérault Y. PLoS Genet. 2012 May;8(5):e1002724. doi: 10.1371/journal.pgen.1002724. Epub 2012 May 31. PMID: 22693452 Free PMC Article Similar articles Select item 22370763 19. Roles of VWRPY motif-mediated gene repression by Runx proteins during T-cell development. Seo W, Tanaka H, Miyamoto C, Levanon D, Groner Y, Taniuchi I. Immunol Cell Biol. 2012 Sep;90(8):827-30. doi: 10.1038/icb.2012.6. Epub 2012 Feb 28. PMID: 22370763 Similar articles Select item 21786422 20. Absence of Runx3 expression in normal gastrointestinal epithelium calls into question its tumour suppressor function. Levanon D, Bernstein Y, Negreanu V, Bone KR, Pozner A, Eilam R, Lotem J, Brenner O, Groner Y. EMBO Mol Med. 2011 Oct;3(10):593-604. doi: 10.1002/emmm.201100168. Epub 2011 Aug 8. PMID: 21786422 Free PMC Article Similar articles A Runx1-Smad6 rheostat controls Runx1 activity during embryonic hematopoiesis. Knezevic K, Bee T, Wilson NK, Janes ME, Kinston S, Polderdijk S, Kolb-Kokocinski A, Ottersbach K, Pencovich N, Groner Y, de Bruijn M, Göttgens B, Pimanda JE. Mol Cell Biol. 2011 Jul;31(14):2817-26. doi: 10.1128/MCB.01305-10. Epub 2011 May 16. PMID: 21576367 Free PMC Article Similar articles Select item 21536859 22. ERG promotes T-acute lymphoblastic leukemia and is transcriptionally regulated in leukemic cells by a stem cell enhancer. Thoms JA, Birger Y, Foster S, Knezevic K, Kirschenbaum Y, Chandrakanthan V, Jonquieres G, Spensberger D, Wong JW, Oram SH, Kinston SJ, Groner Y, Lock R, MacKenzie KL, Göttgens B, Izraeli S, Pimanda JE. Blood. 2011 Jun 30;117(26):7079-89. doi: 10.1182/blood-2010-12-317990. Epub 2011 May 2. PMID: 21536859 Free Article Similar articles Select item 20959602 23. Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models. Pencovich N, Jaschek R, Tanay A, Groner Y. Blood. 2011 Jan 6;117(1):e1-14. doi: 10.1182/blood-2010-07-295113. Epub 2010 Oct 19. PMID: 20959602 Free Article Similar articles Select item 20615577 24. The novel RUNX3/p33 isoform is induced upon monocyte-derived dendritic cell maturation and downregulates IL-8 expression. Puig-Kröger A, Aguilera-Montilla N, Martínez-Nuñez R, Domínguez-Soto A, Sánchez-Cabo F, Martín-Gayo E, Zaballos A, Toribio ML, Groner Y, Ito Y, Dopazo A, Corcuera MT, Alonso Martín MJ, Vega MA, Corbí AL. Immunobiology. 2010 Sep-Oct;215(9-10):812-20. doi: 10.1016/j.imbio.2010.05.018. Epub 2010 Jun 20. PMID: 20615577 Similar articles Select item 20596738 25. In vivo effects of APP are not exacerbated by BACE2 co-overexpression: behavioural characterization of a double transgenic mouse model. Azkona G, Levannon D, Groner Y, Dierssen M. Amino Acids. 2010 Nov;39(5):1571-80. doi: 10.1007/s00726-010-0662-8. Epub 2010 Jul 2. PMID: 20596738 Similar articles Select item 20554226 26. Translation regulation of Runx3. Bone KR, Gruper Y, Goldenberg D, Levanon D, Groner Y. Blood Cells Mol Dis. 2010 Aug 15;45(2):112-6. doi: 10.1016/j.bcmd.2010.04.001. Epub 2010 Jun 2. PMID: 20554226 Similar articles Select item 19233693
    Transcription factor Runx3 is the master regulator of Dorsal Root ganglia TrkC neuron development and as such controls body's proprioception; perception or awareness of position and movement of the body. An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons. Appel E, Weissmann S, Salzberg Y, Orlovsky K, Negreanu V, Tsoory M, Raanan C, Feldmesser E, Bernstein Y, Wolstein O, Levanon D, Groner Y. Genes Dev. 2016 Dec 1;30(23):2607-2622.
    Dynamic combinatorial interactions of RUNX1 and cooperating partners during megakaryocytic differentiation
    Collaboration with:  Amos Tanay Department of Computer Science & Applied Mathematics Eli Zelzer department of Molecular Genetics
    Biological function of the RUNX transcription factors
    Positive and negative transcriptional regulation by Runx3
    The Human Leukemia Associated Transcription Factor RUNX1/AML1 and Down syndrome leukemia

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  • Picture of Dr. Dvir Gur

    Dr. Dvir Gur

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    Unraveling the development and function of specialized crystal-forming cells
    Harnessing insights from uric acid bio-crystallization to better understand kidney stone and gout diseases, and develop new therapeutic approaches
    Exploration and discovery of new bio-organic crystals, architectures and functions in organisms.

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  • Picture of Dr. Jacob (Yaqub) Hanna

    Dr. Jacob (Yaqub) Hanna

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    Deciphering Cellular Reprogramming
    Following a breakthrough that was made in 2006 (by Takahashi & Yamanaka), today we can reverse cellular differentiation, and generate induced pluripotent stem cells from somatic cells by epigenetic “reprogramming”. We investigate what are the dramatic molecular changes happening in the cell during reprogramming and how they are connected to similar in-vivo processes. We pointed out two chromatin regulators that play a role in this process, one is essential for reprogramming (Utx, Mansour et al 2012), and the other (Mbd3/NuRD, Rais et al 2013) is an obstacle, which upon its near-removal the reprogramming becomes dramatically faster and synchronized.
    Understanding Naïve and Primed Pluripotent States
    Being able to generate all cell types, mouse embryonic stem cells are a most valuable tool for research. They can be found in the developing mouse embryo in two distinct states: naïve – in the blastocyst, and primed – in the post-implantation epiblast. These two states are distinct in various aspects, most notable, only naïve cells can contribute efficiently to chimera. Naïve and primed cells can be sustained in-vitro, and are dependent on distinct signaling. In human, naïve stem cells were out of reach for a long time. We investigate the regulation of naïve and primed pluripotent stem cell in mouse and human. Specifically, we were able to maintain human stem cells in a “naive” state, with distinct molecular and functional properties, including enhanced ability to contribute to cross-species mouse chimeric embryos (Gafni et al, 2013). In addition, we found that mRNA methylation has a critical role in facilitating degradation of pluripotent genes, an essential step during the switch from naïve to primed states, both in-vitro and in-vivo (Geula et al, 2014). Our current studies involve elucidating molecular regulation of these states across different species, and define how their molecular architecture dictates their functional competence.
    Human-Mouse Cross-Species Chimerism
    Human stem cells that are sustained in naïve culture conditions, can be injected to mouse blastocyst and contribute to cross-species chimera (Gafni et al, 2013). We investigate these chimeric mice, which are valuable tool for human disease modeling in a whole-organism context.

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  • Picture of Prof. Eran Hornstein

    Prof. Eran Hornstein

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    molecular Neurodegeneration
    RNA and RNA -binding proteins in motor neurons and amyotrophic lateral sclerosis (ALS)
    Human genetics for neuroscience research
    Biomarkers of neurodegeneration
    Multi-omics and machine learning for biomarkers
    biomolecular condensates and stress granules in ALS

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  • Picture of Prof. Adi Kimchi

    Prof. Adi Kimchi

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    Programmed Cell Death, autophagy, RNA translation control, cancer biology
    Deciphering the roles of the DAP genes in programmed cell death, embryonic stem cells and cancer stem cells
    Identifying soft-spots in the networks of programmed cell death and cellular senescence in cancer cells.
    The role of RNA binding proteins in embryonic development
    RNA translation control: structure/function analysis of the DAP5 gene and its mode of action
    New modes of cell death in post-implantation mouse embryos
    Identifying small compound inhibitors pf autophagy

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  • Picture of Prof. Doron Lancet

    Prof. Doron Lancet

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    Bioinformatic tools for disease gene discovery, Origin of life on earth
    Collaboration with:  Prof. Rafi Zidovetzki, University of California Riverside Prof. Philippe Schmitt-Kopplin, Helmholz Center Munich Prof. Daniel Segre, Boston University
    Gene and disease databases, Identification of disease-related mutations by next generation DNA sequencing (NGS), development of software tool for the analysis of NGS results
    Computer simulations of emergence, selection and evolution at the origin of life. Chemical kinetic modeals for mutually catalytic sets, Systems Chemistry

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  • Picture of Dr. Orly Laufman

    Dr. Orly Laufman

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    Molecular and Cell Biology of RNA viruses
    RNA viruses including corona, zika and dengue are a major threat to human health. We study how RNA viruses interact with their host cells and transform them into viral manufactories.
    Our main model is enteroviruses - common viral pathogens that cause severe medical complications in humans, with no available therapeutic treatments.
    We investigate how enteroviruses remodel the structure and function of host organelles to generate an environment favorable to virus replication.
    Another key question we tackle is how enteroviruses, that express only a small number of proteins, take control of human cells with complex protein machineries. We study the different roles of viral proteins and the mechanisms they use to hijack host machineries.
    We aim to piece together the complete program of enterovirus replication. This could lead to the development of new antiviral therapeutics.

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  • Picture of Prof. Shmuel Pietrokovski

    Prof. Shmuel Pietrokovski

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    Developing computational methods for using and identifying protein motifs and applying them for the analysis of particular protein families.
    Developing advanced methods for comparing protein motifs.
    Applying protein motif comparisons for functional and structural predictions and to database annotation.
    Analysis of inteins ("protein splicing" elements) and homing endonucleases.
    Genetic variations in humans and different gene usage in women and men
    Gene variations causing human disease, in particular infertility in men and various cancers.
    Different gene usage in women and men leading to differential selection between the sexes and allowing the accumulation of deleterious mutations.

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  • Picture of Prof. Orly Reiner

    Prof. Orly Reiner

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    Formation of the brain structure in human is a complex process. One of the most striking features of the human brain is characteristic convolutions. These convolutions are lacking in a severe human brain malformation known as lissencephaly (smooth brain).
    Identification of genes that are downstream to Lis1 mutation using microarray technology.
    Study of LIS1 and DCX functions through characterization of protein interactions
    Analysis of the developmental function of LIS1, DCX and Doublecortin-like-kinase using gene targeting in the mouse.
    Functional Analysis of Genes Involved in Lissencephaly.

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  • Picture of Prof. Michel Revel

    Prof. Michel Revel

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    Applications of IL-6 Chimera and Interferon-beta in neurology, hematopoiesis, and oncology.
    Collaboration with:  J. Chebath
    Interleukin-6 Chimera, a superactivator of the gp130 receptor system: role in nerve myelination, neuroprotection and in the development of neuro-glial cells from embryonic tissues and stem cells.
    Collaboration with:  J. Chebath
    Transdifferentiation of neural crest cell derived melanoma into myelinating Schwann cell. Genes controlling cell growth, differentiation, melanogenesis and synthesis of myelin proteins.
    Collaboration with:  J. Chebath
  • Picture of Prof. Maya Schuldiner

    Prof. Maya Schuldiner

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    Uncovering tethers, functions and regulators of membrane contact sites in yeast
    Mitochondria-ER contact sites
    Peroxisome-Lipid Droplet contact sites
    Nucleus-Mitochondria contact sites
    The proteome of contact sites
    Targeting and translocation to Organelles
    Uncovering a role for the Ssh1, the alternative, translocon in yeast
    Deciphering targeting of proteins to mitochondria
    Targeting of membrane proteins to peroxisomes
    Targeting of low-hydrophobicity SS proteins to the ER
    Targeting of proteins to the surface of the ER
    Uncovering new peroxisomal proteins and their functions
    Collaboration with:  Dr. Einat Zalckvar
    Metabolite transport across the peroxisome membrane
    Peroxisome contact sites
    Peroxisome quality control
    Peroxisome targeting
    New peroxisomal enzymes and their functions
    Pexophagy
    Peroxisomes in metabolism
    Novel methodologies for systematic exploration of yeast organelle protein functions
    Creation of versatile yeast libraries
    High throughput electron microscopy techniques
    Translocation sensors

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  • Picture of Prof. Yosef Shaul

    Prof. Yosef Shaul

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    The molecular basis of virus-host cell interaction. How HBV modifies cell behavior.
    Collaboration with:  Charles Rice the Rockefeller university
    proteasomes as a target in cancer therapy
    proteasome composition, dynamics, function and regulation and various conditions.
    proteasomal degradation of intrinsically disordered proteins (IUP or IDP). the concept of degradation by default

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  • Picture of Prof. Rotem Sorek

    Prof. Rotem Sorek

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    Microbial genomics and systems biology
    CRISPR-Cas, an antiviral microbial defense system
    Interactions between bacteria and phages
    Communication between viruses
    RNA-mediated regulation in bacteria
    Computational discovery of novel natural antimicrobials

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  • Picture of Prof. Elazar Zelzer

    Prof. Elazar Zelzer

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    the roles of the VEGF pathway in different steps during skeletal development.
    Studying the role of mechanical load on embryonic bone development

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