缅北禁地

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Staff Profile

Professor Jonathan Higgins

Professor of Eukaryotic Molecular Cell Biology; Director of Research Career Development; Theme Lead for Cells, Genes and Molecules

  • Telephone: +44 (0) 191 208 7431
  • Address: 缅北禁地 Biosciences Institute,
    M2.043, Cookson Building,
    Framlington Place,
    缅北禁地 upon Tyne,
    Tyne and Wear
    NE2 4HH
Background

Education:

1987-1991 BA, Biochemistry, University of Oxford

1991-1995 DPhil, University of Oxford

Postdoctoral training:

1995-1997 Research Fellow in Medicine, Brigham and Women's Hospital, Harvard Medical School, USA

Previous Appointments:

1997-2002 Instructor in Medicine, Brigham and Women's Hospital, Harvard Medical School, USA

2003-2014 Assistant Professor of Medicine, Brigham and Women's Hospital, Harvard Medical School, USA

2003-2014 Member, Cancer Cell Biology Program, Dana-Farber/Harvard Cancer Center, USA

2006-2014 Member, Biological and Biomedical Sciences Graduate Program, Harvard Medical School, USA

2017-2019 Deputy Dean of Research and Innovation, Faculty of Medical Sciences, 缅北禁地

Funding:

Over the years, our work has been funded by a Wellcome Trust Investigator Award, a Royal Society Wolfson Research Merit Award, and by the BBSRC, the MRC, Cancer Research UK/Children with Cancer UK, the National Institutes of Health (USA), the American Cancer Society, the Leukemia and Lymphoma Society, the Crohn's and Colitis Foundation, Worldwide Cancer Research, and the JGW Patterson Foundation.

Google Scholar:

Research

Our laboratory focuses on cell division, a process that requires a dramatic and highly orchestrated change in cell structure, including the condensation of chromosomes, their alignment on a bipolar spindle, the synchronous movement of exactly half of the chromosomes to opposite poles of the cell, and then cytokinesis (dividing the cell into two).

To accomplish cell division with high fidelity requires tight control of chromosome structure, including the displacement of proteins that might hinder chromosome segregation, and the recruitment of proteins that allow the chromosomes to condense and be “bi-oriented” on the spindle. Through all of this change, the cell also retains markers (“bookmarks”) on chromosomes that can “remember” whether genes are active or inactive so that they can be returned to their original states once cell division is complete. These events must be precisely controlled in location and timing. Our laboratory studies these control mechanisms. In particular, we study how chromatin modifications help determine where and when key regulatory factors can bind to chromosomes. We also study how defects in chromosome structure influence how chromosomes are segregated.

We are particularly interested in (1) how histone kinases such as Haspin and Aurora B control cell division in human cells, and (2) how dicentric chromosomes influence segregation and genome stability. In both cases, we aim to understand how these process contributes to the generation of cancer and birth defects, and how they can be exploited for disease therapy. In the future, we aim to determine the roles of additional histone modifications in mitosis and to develop a genome-wide understanding of how these marks are deposited to regulate both chromosome segregation and the inheritance of epigenetic information during cell division. As a spin off as this research, we are also interested in developing new approaches to identify kinases that are responsible for uncharacterised phosphorylation events in cells.

I am Theme Lead for Cells, Genes and Molecules, and a member of the 缅北禁地 Centre for Cancer.

Teaching


MRes Molecular Cell Biology in Health and Disease (Programme Lead)

MMB8008: MRes Chromosome Biology and Cell Cycle Control in Health and Disease (Module Lead)

MMB8099: MRes Research Projects

CMB3000: Undergraduate Research Projects

CMB4099: MSci Research Projects

BMS2002: BSc Cell Biology and Disease


Publications

  • Articles

    • Harris RJ, Heer M, Levasseur MD, Cartwright TN, Weston B, Mitchell JL, Coxhead JM, Gaughan L, Prendergast L, Rico D, Higgins JMG. . Nature Communications 2023, 14, 7243.
    • Exton J, Higgins JMG, Chen J. . Scientific Reports 2023, 13, 12826.
    • Luo M, Yang W, Cartwright TN, Higgins JMG, Chen J. . Langmuir 2022, 38(2), 620-628.
    • Cartwright TN, Meyer SK, Higgins JMG. . SLAS Discovery 2022, 27(8), 471-475.
    • Gillani SQ, Reshi I, Nabi N, Nisa MU, Sarwar Z, Bhat S, Roberts TM, Higgins JMG, Andrabi S. . Journal of Cell Science 2022, 135(3), jcs258831.
    • Cartwright TN, Harris RJ, Meyer SK, Mon AM, Watson NA, Tan C, Marcelot A, Wang F, Zinn-Justin S, Traktman P, Higgins JMG. . Scientific Reports 2022, 12, 11210.
    • Papini D, Levasseur MD, Higgins JMG. . Cell Reports 2021, 37(6), 109818.
    • Thomas C, Wetherall B, Levasseur MD, Harris RJ, Kerridge ST, Higgins JMG, Davies OR, Madgwick S. . Nature Communications 2021, 12(1), 4322.
    • Prendergast L, McClurg UL, Hristova R, Berlinguer Palmini R, Greener S, Veitch K, Hernández-López I, Pasero P, Rico D, Higgins JMG, Gospodinov A, Papamichos-Chronakis M. . Nature Communications 2020, 11, 4534.
    • Watson NA, Cartwright TN, Lawless C, Cámara-Donoso M, Sen O, Sako K, Hirota T, Kimura H, Higgins JMG. . Nature Communications 2020, 11, 1684.
    • Seibert M, Krüger M, Watson NA, Sen O, Daum JR, Slotman JA, Braun T, Houtsmuller AB, Gorbsky GJ, Jacob R, Kracht M, Higgins JMG, Schmitz ML. . Journal of Cell Biology 2019, 218(4), 1164-1181.
    • Levasseur MD, Thomas C, Davies OR, Higgins JMG, Madgwick S. . Developmental Cell 2019, 48, 1-18.
    • Sen O, Saurin AT, Higgins JMG. . Scientific Reports 2018, 8, 7898.
    • Papini D, Langemeyer L, Abad MA, Kerr A, Samejima I, Eyers PA, Jeyaprakash AA, Higgins JMG, Barr FA, Earnshaw WC. . Nature Communications 2015, 6, 7678.
    • Pores Fernando AT, Andrabi S, Cizmecioglu O, Zhu C, Livingston DM, Higgins JMG, Schaffhausen BS, Roberts TM. . Oncogene 2015, 34(19), 2483-2492.
    • Zhou L, Tian X, Zhu C, Wang F, Higgins JMG. . EMBO Reports 2014, 15, 273-281.
    • Higgins JMG, Herbert M. . PLoS Genetics 2013, 9, e1003829.
    • Cuny GD, Ulyanova NP, Patnaik D, Liu JF, Lin H, Auerbach K, Ray SS, Xian J, Glicksman MA, Stein RL, Higgins JMG. . Bioorganic and Medicinal Chemistry Letters 2012, 22(5), 2015-2019.
    • Niedzialkowska E, Wang F, Porebski PJ, Minor W, Higgins JMG, Stukenberg PT. . Molecular Biology of the Cell 2012, 23(8), 1457-1466.
    • Wang F, Ulyanova NP, Daum JR, Patnaik D, Kateneva AV, Gorbsky GJ, Higgins JMG. . Journal of Cell Biology 2012, 199(2), 251-268.
    • Czakai K, Müller K, Pepe G, Mosesso P, Jeanclos E, Gohla A, Patnaik D, Dekant W, Higgins JMG, Mally A. . Toxicological Sciences 2011, 122(2), 317-329.
    • Wang F, Ulyanova NP, van der Waal MS, Patnaik D, Lens SM, Higgins JMG. . Current Biology 2011, 21(12), 1061-1069.
    • Cuny GD, Robin M, Ulyanova NP, Patnaik D, Pique V, Casano G, Liu JF, Xian J, Glicksman MA, Stein RL, Higgins JMG. Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors. Bioorganic and Medicinal Chemistry Letters 2010, 20, 3491-3494.
    • Wang F, Dai J, Daum JR, Niedzialkowska E, Banerjee B, Stukenberg PT, Gorbsky GJ, Higgins JM. . Science 2010, 330(6001), 231-235.
    • Varier RA, Outchkourov NS, de Graaf P, van Schaik FMA, Ensing HJL, Wang F, Higgins JMG, Kops GJPL, Timmers HThM. A phospho/methyl switch at histone H3 regulates TFIID association with mitotic chromosomes. EMBO Journal 2010, 29, 3967-78.
    • Dai J, Kateneva AV, Higgins JMG. Studies of Haspin-depleted cells reveal that spindle-pole integrity requires chromosome cohesion. Journal of Cell Science 2009, 122, 4168-4176.
    • Eswaran J, Patnaik D, Filippakopoulos P, Wang F, Stein RL, Murray JW, Higgins JMG, Knapp S. . Proceedings of the National Academy of Sciences of the United States of America 2009, 106(48), 20198–20203.
    • Metzger E, Yin N, Wissmann M, Kunowska N, Fischer K, Friedrichs N, Patnaik D, Higgins JMG, Potier N, Scheidtmann KH, Buettner R, Schüle R. Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation. Nature Cell Biology 2008, 10, 53-60.
    • Patnaik D, Xian J, Glicksman MA, Cuny GD, Stein RL, Higgins JMG. Identification of Small Molecule Inhibitors of the Mitotic Kinase Haspin by High Throughput Screening using a Homogeneous Time-Resolved Fluorescence Resonance Energy Transfer Assay. Journal of Biomolecular Screening 2008, 13, 1025-1034.
    • Parisini E, Higgins JMG, Liu JH, Brenner MB, Wang JH. The crystal structure of human E-cadherin domains 1 and 2, and comparison with other cadherins in the context of adhesion mechanism. Journal of Molecular Biology 2007, 373, 401-411.
    • Kiener HP, Stipp CS, Allen PG, Higgins JMG, Brenner MB. The cadherin-11 cytoplasmic juxta-membrane domain promotes α-catenin turnover at adherens junctions and intercellular motility. Molecular Biology of the Cell 2006, 17, 2366-76.
    • Dai J, Sullivan BA, Higgins JMG. Regulation of mitotic chromosome cohesion by Haspin and Aurora B. Developmental Cell 2006, 11, 741-750.
    • Dai J, Sultan S, Taylor SS, Higgins JMG. The kinase haspin is required for mitotic histone H3 threonine-3 phosphorylation and normal metaphase chromosome alignment. Genes and Development 2005, 19, 472-488.
    • Hintermann E, Yang N, O'Sullivan D, Higgins JMG, Quaranta V. Integrin α6β4/erbB2 complex inhibits haptotaxis by upregulating E-cadherin cell-cell junctions in keratinocytes. Journal of Biological Chemistry 2004, 280, 8004-80015.
    • Valencia X, Higgins JMG, Kiener HP, Lee DM, Pobrebarac TA, Dascher CC, Mizoguchi E, Simmons B, Patel DD, Bhan AK, Brenner MB. Cadherin-11 provides specific cellular between fibroblast-like synoviocytes. Journal of Experimental Medicine 2004, 200, 1673-1679.
    • Higgins JMG. The Haspin gene: location in an intron of the Integrin αE gene, associated transcription of an Integrin αE-derived RNA and expression in diploid as well as haploid cells. Gene 2001, 267, 55-69.
    • Bono P, Rubin K, Higgins JMG, Hynes RO. Layilin, a novel integral membrane protein, is a hyaluronan receptor. Molecular Biology of the Cell 2001, 12, 891-900.
    • Strauch UG, Mueller RC, Li XY, Cernadas M, Higgins JMG, Binion DG, Parker CM. Integrin αE(CD103)β7 mediates adhesion to intestinal microvascular endothelial cell lines via an E-cadherin independent mechanism. Journal of Immunology 2001, 166, 3506-3514.
    • Higgins JMG. Haspin-like proteins, a new family of evolutionarily conserved putative eukaryotic protein kinases. Protein Science 2001, 10, 1677-1684.
    • Higgins JMG, Cernadas M, Tan K, Irie A, Wang JH, Takada Y, Brenner MB. The Role of α and β Chains in Ligand Recognition by β7 Integrins. Journal of Biological Chemistry 2000, 275, 25652-25664.
    • Taraszka KS, Higgins JMG, Tan K, Mandelbrot DA, Wang JH, Brenner MB. Molecular Basis for Leukocyte Integrin αEβ7 Adhesion to Epithelial (E)-Cadherin. Journal of Experimental Medicine 2000, 191, 1555-1567.
    • Li Z, Kim SH, Higgins JMG, Brenner MB, Sacks D. IQGAP1 and Calmodulin Modulate E-cadherin Function. Journal of Biological Chemistry 1999, 274, 37885-37892.
    • Higgins JMG, Mandelbrot DA, Shaw SK, Russell GJ, Murphy EA, Chen YT, Nelson WJ, Parker CM, Brenner MB. Direct and regulated interaction of integrin αEβ7 with E-cadherin. Journal of Cell Biology 1998, 40, 197-210.
    • Higgins JMG, Wiedemann H, Timpl R, Reid KBM. Characterization of Mutant Forms of Recombinant Human Properdin Lacking Single Thrombospondin Type I Repeats: Identification of modules important for function. Journal of Immunology 1995, 155, 5777-5785.
    • Nolan KF, Kaluz S, Higgins JMG, Goundis D, Reid KBM. Characterization of the human properdin gene. Biochemical Journal 1992, 287, 291-297.

  • Book Chapters

    • Watson NA, Higgins JMG. . In: Binda O; Fernandez-Zapico M, ed. Chromatin Signaling and Diseases. Waltham, MA: Elsevier Inc, 2016, pp.75–94.
    • Hadley GA, Higgins JMG. . In: I Domain Integrins. Dordrecht: Springer, 2014, pp.97-110.
    • Sacks DB, Higgins JMG. Cadherin Signaling. In: Lennarz, WJ; Lane, MD, ed. Encyclopedia of Biological Chemistry. Academic Press/Elsevier Science, 2004.
    • Kilshaw PJ, Higgins JMG. Integrin αEβ7: molecular features and functional significance in the immune system. In: Gullberg, D, ed. I-domains in integrins. Georgetown, TX: Landes Bioscience/Springer, 2002.

  • Reviews

    • Zhou X, Higgins JMG, Wang F. . Science China Life Sciences 2025.
    • Stephenson EH, Higgins JMG. . Frontiers in Pharmacology 2023, 14, 1310135.
    • Schmitz ML, Higgins JMG, Seibert M. . Cell Cycle 2020, 19(6), 625-641.
    • Higgins JMG, Prendergast L. . Developmental Cell 2016, 36(5), 477-478.
    • Wang F, Higgins JMG. . Trends in Cell Biology 2013, 23(4), 175-184.
    • Higgins JMG. . Current Biology 2013, 23(19), R883-R885.
    • Higgins JMG. . Chromosoma 2010, 119, 137-147.
    • Kateneva AV, Higgins JMG. . Developmental Cell 2009, 17(3), 303-305.
    • Higgins JMG. . UCSD-Nature Molecule Pages 2008.
    • Dai J, Higgins JMG. . Cell Cycle 2005, 4(5), 665-668.
    • Higgins JMG. Structure, function and evolution of haspin and haspin-related proteins, a distinctive group of eukaryotic proteins kinases. Cellular and Molecular Life Sciences 2003, 60, 446-462.
    • Kilshaw PJ, Higgins JMG. Alpha E: no more rejection?. Journal of Experimental Medicine 2002, 196, 873-876.
    • Agace WW, Higgins JMG, Sadasivan B, Brenner MB, Parker CM. . Current Opinion in Cell Biology 2000, 12(5), 563-568.