Dr. Tzachi Hagai

Tzachi Hagai is a senior lecturer in the School of Molecular Cell Biology & Biotechnology since 2019.  During his PhD he has used computational tools in bioinformatics and modelling to study the regulation and evolution of protein ubiquitination. In his postdoctoral studies, he has focused on host-pathogen co-evolution. In the first part of his postdoc, he has studied the pathogen side, asking how viruses evolved to interact with host proteins, using virological replication assays and protein network analysis. In the second part of his postdoctoral work, he has focused on the evolution of host immune response in mammals, using comparative genomics, single-cell transcriptomics and in vitro immune stimulation assays.

2004 BSc Biology & Chemistry, Hebrew University of Jerusalem

2012 PhD Chemistry, Computational biophysics of proteins, Weizmann Institute

2013-2014 Postdoctoral fellow, Evolution of host-virus interactions, UCSF, USA

2014-2019 Postdoctoral fellow, Evolution of mammalian innate immunity, European Bioinformatics Institute & Wellcome Sanger Institute, Cambridge, UK

Our research goals are to understand how the evolutionary arms race between pathogens and their hosts has shaped the immune system and influenced human and animal susceptibility to infectious diseases. For this we combine analytical tools in evolutionary genomics and bioinformatics with immunological stimulations and in vitro infection assays to compare the immune response between species. Our long-term vision is to harness diverse defence mechanisms from across the vertebrate clade to devise new therapeutics against pathogens. 

Davidson S, Efremova M, Riedel A, Mahata B, Pramanik J, Huuhtanen J, Kar G, Vento-Tormo R, Hagai T, Chen X, Haniffa MA, Shields JA & Teichmann SA. A dynamic stromal niche supports tumour growth during tumour evolution.  Preprint: bioRxiv. DOI: https://doi.org/10.1101/467225.

McCarthy DJ, Rostom R, Huang Y, Kunz DJ, Danecek P, Bonder MJ, Hagai T, HipSci Consortium, Wang W, Gaffney DJ, Simons BD, Stegle O & Teichmann SA. Cardelino: Integrating whole exomes and single-cell transcriptomes to reveal phenotypic impact of somatic variants. Preprint: bioRxiv. DOI: https://doi.org/10.1101/413047.  

Hagai T, Chen X, Miragaia RJ, Rostom R, Gomes T, Kunowska N, Henriksson J, Park J, Proserpio V, Donati G, Bossini-Castillo L, Braga FAV, Naamati G, Fletcher J, Stephenson E, Vegh P, Trynka G, Kondova I, Dennis M, Hanniffa M, Nourmohammad A, Lassig M & Teichmann SA. (2018) Gene expression variability across cells and species shapes innate immunity. Nature. Nov;563(7730):197-202.  DOI: 10.1038/s41586-018-0657-2. Highlighted in: Nature Reviews Immunology, Nature Immunology, Cell.

Mor N, Rais Y, Sheban D, Peles S, Aguilera-Castrejon A, Zviran A, Elinger D, Viukov S, Geula S, Krupalnik V, Zerbib M, Chomsky E, Lasman L, Shani T, Bayerl J, Gafni O, Hanna S, Buenrostro JD, Hagai T, Masika H, Vainorius G, Bergman Y, Greenleaf WJ, Esteban MA, Elling U, Levin Y, Massarwa R, Merbl Y, Novershtern N & Hanna JH. (2018) Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency. Cell Stem Cell. DOI: 10.1016/j.stem.2018.07.004

Miragaia RJ, Teichmann, SA, Hagai T. (2017) Single-cell insights into transcriptomic diversity in immunity. Curr Opin Sys Bio, 5:63-71. DOI: 10.1016/j.coisb.2017.08.003

Y Gavrilov, Hagai T & Levy Y.  (2015) Nonspecific yet decisive: Ubiquitination can affect the native‐state dynamics of the modified protein. Protein Science 24 (10): 1580-1592. DOI: 10.1002/pro.268

Gitlin L, Hagai T, LaBarbera A, Solovey M & Andino R. (2014) Rapid evolution of virus sequences and functions through intrinsically disordered regions. PLoS Pathogens 10 (12): e1004529. DOI: 10.1371/journal.ppat.1004529

Hagai T, Azia A, Babu MM & Andino R. (2014) Use of host-like peptide motifs in viral proteins is a prevalent strategy in host-virus interactions. Cell Reports 7(5):1729-39. DOI: 10.1016/j.celrep.2014.04.052

Tsvetkov P, Myers N, Eliav R, Adamovich Y, Hagai T, Adler J, Navon A & Shaul Y. (2014). NADH binds and stabilizes the 26S proteasomes independent of ATP. J Biol Chem 289(16):11272-81. DOI: 10.1074/jbc.M113.537175

Rais Y, Zviran A, Geula S, Gafni O, Chomsky E, Viukov S, AlFatah Mansour A, Caspi I, Krupalnik V, Zerbib M, Maza I, Mor N, Baran D, Weinberger L, Jaitin DA, Lara-Astiaso D, Blecher-Gonen R, Shipony Z, Mukamel Z, Hagai T, Gilad S, Amann-Zalcenstein D, Tanay A, Amit I, Novershtern N & Hanna JH. (2013). Deterministic direct reprogramming of somatic cells to pluripotency. Nature 502, 65–70. DOI: 10.1038/nature1258

Dagan S, Hagai T, Gavrilov Y, Kapon R, Levy Y & Reich Z. (2013). Stabilization of a protein conferred by an increase in folded state entropy. Proc Natl Acad Sci U S A 110, 10628-33. DOI: 10.1073/pnas.1302284110Hagai T, Azia A, Trizac E & Levy Y. (2012). Modulation of folding kinetics of repeat proteins: Interplay between intra- and inter-domain interactions. Biophys J 103, 1555-1565. DOI: 10.1016/j.bpj.2012.08.018

Hagai T, Toth-Petroczy A, Azia A & Levy Y. (2012). The origins and evolution of ubiquitination sites. Mol Biosyst 8, 1865-77. DOI: 10.1039/c2mb25052g

Hagai T, Azia A, Toth-Petroczy A & Levy Y. (2011). Intrinsic disorder in ubiquitination substrates. J Mol Biol 412, 319-24. DOI: 10.1016/j.jmb.2011.07.024

Hagai T & Levy Y. (2010). Ubiquitin not only serves as a tag but also assists degradation by inducing protein unfolding. Proc Natl Acad Sci U S A 107, 2001-6. DOI:10.1073/pnas.0912335107

Shental D, Arviv O, Hagai T & Y Levy. (2010). Folding of conjugated proteins. Annu Rep Comput Chem 6, 263-277.

Hagai T & Levy Y. (2008). Folding of elongated proteins: conventional or anomalous?  J Am Chem Soc 130, 14253-62. DOI: 10.1021/ja804280p

Hagai T, Cohen M & Bloch G. (2007). Genes encoding putative Takeout/juvenile hormone binding proteins in the honeybee (Apis mellifera) and modulation by age and juvenile hormone of the takeout-like gene GB19811. Insect Biochem Mol Biol 37, 689-701. DOI: 10.1016/j.ibmb.2007.04.002