Professor Eric C. Schirmer (PhD)

  • Institute of Cell Biology
  • School of Biological Sciences

Contact details

Address

Street

Room 5.22
Michael Swann Building
Kings Buildings
Max Born Crescent

City
Edinburgh
Post code
EH9 3BF

Biography

Background

Education:

1987    B.A., The College, The University of Chicago, Chicago, Illinois, USA

1988    Graduate courses at the Foundation for Advanced Education in the Sciences at the National Institutes of Health while working at NIAID, Bethesda, Maryland, USA

1997    Ph.D., Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois, USA.  Dissertation: Mutational and Biochemical Analysis of Saccharomyces cerevisiae Hsp104 Reveals Critical Functions and Functional Domains, Thesis Advisor: Susan L. Lindquist, Professor, Howard Hughes Medical Institute Investigator, Member National Academy of Sciences, former Director of the Whitehead Institute for Biomedical Research.  

 

Chronology of Employment:

2017-current   Professor of Nuclear Envelope Biology

2012-2017      Reader

2005-2018      Wellcome Trust Senior Research Fellow

2004-current   Group Leader, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK

1997-2004      Post-doctoral work, Department of Cell Biology, The Scripps Research      Institute, La Jolla, California, USA, Laboratory of Larry Gerace 

1988-1990      Biologist, grade 9, NIH, National Institute of Allergy and Infectious Diseases (NIAID), Laboratory of Viral Diseases, Supervisor Niza Frenkel      

1984-1984      Summer Research Internship, Eli Lilly & Co, Indianapolis, Indiana, USA  

 

Scientific Society Membership:

American Society for Cell Biology 1995- current     

British Society for Cell Biology 2004- 2012; 2015- current     

Member of European Consortium on Lipodystrophy (EClip) 2014- current     

Biochemical Society 2015- current     

Genetics Society 2016- current     

European Laminopathies Network 2018- current

Undergraduate teaching

SFP (Course organiser Paul McLaughlin)

Cell Biology From Fundamental Mechanisms to Human Disease, Honours (Course Organiser since 2015)

Membrane Biology, Honours (Course Organiser since 2009)

Science Ethics (Course Organiser since 2015)

Current PhD students supervised

Qingqin Ji, PhD student (matriculated 2021).

Yuwen Gao, PhD student (matriculating 2023).

Past PhD students supervised

PhD students (year graduated):

Charles Dixon, Wellcome Trust 4-year PhD student (2021)

Aishwarya Sivakumar, Darwin Trust student (2020)

Nikolaj Zuleger, Staff Scholarship Scheme (2012) 

Dzmitry G. Batrakou, Darwin Trust student (2012)

Michael I. Robson, Wellcome Trust 4-year PhD student (2015)

Phu Le Thanh, MRC student (2017)

Natalia Saiz Ros, University of Edinburgh Principal’s student (2017)

Alexandr Makarov, University of Edinburgh Principal’s student (2017)

Andrea Rizzotto, Darwin Trust student (2019)

 

MSc students (year graduated):

Nikolaj Zuleger, Lausitz University of Applied Sciences (2008) obtained 1st

Gerlinde Regina Otti, Universitat Wien (2010) obtained 1st

Keerthi Sri Jagadeesh Kumar, Biotechnology programme University of Edinburgh (2012)

Hannah Elam, University of Edinburgh (2013)

Lior Pytowski, Universite La Rochelle (2016) obtained 1st

Charlotte Capitanchik, Biotechnology programme University of Edinburgh, (2018) obtained 1st

Dario Barreiros, University of Edinburgh (2020)

Muhunden Jayakrishnan Nallappa, IISER Pune (2020)

 

Honours/ Diploma Students Trained: 17

First degrees obtained by 8, also winners of the Cell Biology and Molecular Biology 4 Top Student Prize, Genetics and Molecular Genetics 4 Top Student Prize, Genetics and Molecular Biology 4 Top Student Prize, and Society of Biology Top Student Award.

Research summary

Nuclear envelope transmembrane (NET) protein regulation of tissue specific genome organisation in differentiation and disease

Mutations in widely expressed nuclear envelope (NE) proteins cause many distinct diseases with tissue-specific pathologies including muscular dystrophies, lipodystrophies, neuropathy, dermopathy, and premature-aging syndromes. This raised the question: how could mutations in the same ubiquitous protein cause distinct diseases affecting different tissues? Hypothesizing that tissue-specific partners mediate the tissue-specific pathologies, we identified candidate partners with proteomics. The NE connects on the inside to chromatin and genome organisation is disrupted in patient cells. If our hypothesis is correct, it follows that these tissue-specific NETs might direct tissue-specific patterns of genome organisation with consequences for gene expression and we have found this to be the case.

We found three muscle-specific NETs that re-position genes to the NE that are needed early in myogenesis, but subsequently become inhibitory and must be tightly shut down. Their combined knockdown blocks myogenesis. Thus, NE gene recruitment enables tighter regulatory control. Importantly, we found mutations in these muscle NETs in unlinked Emery-Dreifuss muscular dystrophy patients, further arguing the importance of this novel regulatory mechanism. We have found similar effects with a fat-specific NET in adipogenesis and found that mice lacking this protein have difficulty producing fat, become insensitive to insulin, have metabolic dysfunction and a general lipodystrophy phenotype.

It appears that NE connections can also influence gene activities in the nuclear interior as during lymphocyte activation we found that released genes that were flanked by unchanging NE-associated regions remained within <0.8 µm from the NE, presumably because the flanking contacts restrict their diffusion and thus promote their association in chromosome compartments in what we call the “constrained diffusion” hypothesis. We showed that several genes and an enhancer up to 14 Mb away from one another are all released upon lymphocyte activation and associate in A2 sub-compartments. This type of regulation could contribute temporal control to lymphocyte activation.

Other lines of investigation include: 1) Studying the structure of intermediate filament lamins with the Rappsilber lab. 2) Investigating NET effects on nuclear size changes in several cancer types and screening for small molecules targeting this with the Auer and Tyers labs. Nuclear size changes mark increased disease severity and this is also tissue- specific. 3) Investigating STING (NET23) function at the NE, finding NE-specific partners that contribute to innate immune responses 4) Investigating how herpesviruses escape through the NE, finding that vesicle fusion proteins in the NE are needed for efficient virus nuclear egress.

Current project grants

Muscular Dystrophy UK project grant: Identification of convergent gene regulatory pathways as novel targets in Emery-Dreifuss muscular dystrophy.
18GRO-PG24-0248, 01/2019-12/2020, £145,185

Medical Research Council project grant: Nuclear envelope directed genome organization in myogenesis and Emery-Dreifuss muscular dystrophy.
MR/R018073/1, 08/2018-07/2021, £714,043

Past project grants

Wellcome Trust Senior Research Fellowship: Nuclear envelope transmembrane protein regulation of tissue-specific genome organization and cell cycle regulation.
095209Z/10/Z, 08/2011-07/2016, £2,089,698

Wellcome Trust Project Grant: Identity and role of integral membrane proteins of nuclear envelope precursor vesicles in membrane fusion and nuclear pore assembly, Co-Investigator with Principal Investigator Christopher J Hutchison, Durham University.
086169, 01/01/2009-12/31/2011, £222,069

Wellcome Trust Senior Research Fellowship: The role of the nuclear envelope in genome architecture and cellular differentiation
076616, 08/2005-07/2011, £1,442,969

Organiser

2019 September 2-5 — 9th Nuclear Envelope Disease and Chromatin Organisation Meeting and 3rd International Meeting on Laminopathies, co-organized with main organizer Qiuping Zhang, London, UK

2019 August 25-29 — Nucleo-cytoplasmic Transport International Meeting, co-organized with Mark Field, Peebles Hydro, Peebles, UK

2019 April 22-25 — Integrative Biology: from molecules to ecosystems in extreme environments. EMBO Workshop (€34,000 award) co-organized with Rodrigo Gutierrez, Santiago, Chile

2018 February 23 — Cross-College Meeting in Science and Engineering, University of Edinburgh

2017 November 20 — Cross-School Fellows meeting, University of Edinburgh

2017 August 22-25 — The Pleiotropic Nuclear Envelope, Biochemical Society Focused International meeting (£30,000 award), co-organized with Sue Shackleton and Edgar Gomes, Edinburgh, UK.

2015 November 27 — Cross-School Fellows meeting, University of Edinburgh

2013 September 25-26 —6th Nuclear Envelope and Chromatin Organisation meeting co-organized with main organizer Joanna Bridger at Brunel, London, UK.

2007 April 2 — Nuclear Envelope and Chromatin Organisation meeting at the University of Edinburgh

In the press

Podcast

Podcast about Makarov et al., 2019 Nature Communications study generating a new model for how the lamin polymer is so elastic. 

BioPOD February 2020: Lamin-A Proteins

Beyond Discipline

Outreach film about interdisciplinary science that was made by Dr Alexander Kagansky and Paul Maguire and featured interviews with myself and several lab members along with those from several other labs including Nobel Laureate Peter Higgs.  It was shown at UNESCO World Science Day and in over 100 universities across Russia and can be found at

Global Young Academy - Beyond Discipline Video 

Watch Beyond Discipline Video

Research in a Nutshell

Research in a Nutshell Video

 

$subject of patent application; *commented on by popular press; Ffaculty of 1000; Cnoted on journal cover. According to Google Scholar: >6,000 citations; 33 papers with >50 citations(GS50); 20 papers with >100 citations (GS100); 4 papers with >500 citations (GS500).

Refereed Research Reports

Rizzotto, A., Tollis, S., Pham, N. T., Wildenhain, J., Zuleger, N., Keys, J. T., Batrakou, D., Culley, J., Zheng, S., Lammerding, J., Carragher, N. O., Brunton, V. G., Auer, M., Tyers, M., and Schirmer, E. C.  Chemical-genetic interrogation of nuclear size control reveals cancer-specific effects on cell migration and invasion. Posted on BioRxiv https://biorxiv.org/cgi/content/short/2020.01.10.902148v1 Submitted.

Mudumbi, K. C., Czapiewski, R., Luo, W., Ngo, C., Ospina, V., Schirmer, E. C., and Yang, W.  (2020)  Transmembrane proteins transit two distinct channels of the nuclear pore complex into the nucleus. Nat Commun. 11(1):2184. doi: 10.1038/s41467-020-16033-x. PMID:32366843

*Meinke, P., Kerr, A. R. W., Czapiewski, R., de las Hera, J. I., Dixon, C. R., Harris, E., Kolbel, H., Muntoni, F., Schara, U., Straub, V., Schoser, B., Wehnert, M., and Schirmer, E. C. (2020) A multistage sequencing strategy pinpoints novel candidate alleles for Emery-Dreifuss muscular dystrophy and supports gene misregulation as its pathomechanism. EbioMedicine 102587.doi: 10.1016/j.ebiom.2019.11.048. (Original version on BioRxiv http://biorxiv.org/cgi/content/short/705780v1). Highlighted with commentary by Hui Xiong: https://www.thelancet.com/action/showPdf?pii=S2352-3964%2819%2930835-7 c. PMID:31862442

Makarov, A. A., Zou, J., Houston, D. R., Spanos, C., Solovyova, A. S., Cardinale-Peralta, C., Rappsilber, J., and Schirmer, E. C. (2019) Lamin A molecular compression and sliding as mechanisms behind nucleoskeleton elasticity. Nat Communs 10(1), 3056 doi 10.1038/s41467-019-11063-6. PMID:31296869

*Duan, J., Navarro-Dorado, J., Clark, J. H., Kinnear, N. P., Meinke, P., Schirmer, E. C., and Evans, A. M.  (2019) The cell-wide web coordinates cellular processes by directing site-specific Ca2+ flux across cytoplasmic nanocourses. Nat. Commun. 10(1), 2299 doi 10.1038/s41467-019-19955-w. PMID:31127110

Saiz-Ros, N., Czapiewski, R., Epifano, I., Stevenson, A., Swanson, S. K., Dixon, C. R., Zamora, D. B., McElwee, M., Vijayakrishnan, S., Richardson, C. A., Dong, L., Kelly, D. A., Pytowski, L., Goldberg, M. W., Florens, L., Graham, S. V., and Schirmer, E. C. (2019) Host vesicle fusion protein VAPB contributes to the nuclear egress stage of herpes simplex virus type-1 (HSV-1) replication. Cells 8(2), pii: E120 doi: 10.3390/cells8020120. (Original version on BioRxiv https://doi.org/10.1101/088633.) PMID:30717447

Bikkul, M. U., Faragher, R. G. A., Worthington, G., Meinke, P., Kerr, A. R. W., Sammy, A., Riyahi, K., Horton, D., Schirmer, E. C., Hubank, M., Kill, I. R., Anderson, R. M., Slijepcevic, P., Makarov, E., and Bridger, J. M. (2019) Telomere elongation through hTERT immortalization leads to chromosome repositioning in control cells and genomic instability in Hutchison-Gilford progeria syndrome fibroblasts, expressing a novel SUN1 isoform. Genes Chromosomes Cancer 58(6), 341-356. PMID:30474255

Gatticchi, L., de las Heras, J. I., Roberti, R., and Schirmer, E. C.  (2019) Optimization of DamID for use in primary cultures of mouse hepatocytes. Methods 157, 88-99. PMID:30445179

Capitanchik, C., Dixon, C., Swanson, S. K., Florens, L., Kerr, A. R. W., and Schirmer, E. C. (2018) Analysis of RNA-Seq datasets reveals enrichment of tissue-specific splice variants for nuclear envelope proteins.  Nucleus 9(1), 410-430. PMID:29912636

Zhiteneva, A., Bonfiglio, J. J., Makarov, A. A., Colby, T., Vagnarelli, P., Schirmer, E. C., Matic, I., and Earnshaw, W. C.   (2017)  Mitotic post-translational modifications of histones promote chromatin compaction in vitro. Open Biol 7(9), pii: 170076. PMID: 28903997

FRobson, M. I., de las Heras, J. I., Czapiewski, R., Sivakumar, A., Kerr, A. R. W., and Schirmer, E. C.  (2017)  Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments. Genome Res doi: 10.1101/gr.212308.116. (Original version on BioRxiv https://doi.org/10.1101/062224.) PMID: 28424353

Dixon, C. R., Platani, M., Makarov, A. A., and Schirmer, E. C.  (2017)  Microinjection of antibodies targeting the lamin A/C histone-biding site blocks mitotic entry and reveals separate chromatin interactions with HP1, CenpB and PML.  Cells 6(2), pii: E9. doi: 10.3390/cells6020009. PMID: 28346356

Le Thanh, P., Meinke, P., Korfali, N., Srsen, V., Robson, M. I., Wehnert, M. Schoser, B., Sewry, C. A., and Schirmer, E. C.  (2017)  Immunohistochemistry on a panel of Emery-Dreifuss muscular dystrophy samples reveals nuclear envelope proteins as inconsistent markers for pathology. Neuromuscul Disord 27(4), 338-351. PMID: 28214269

de las Heras, J. I., Zuleger, N., Batrakou, D. G., Czapiewski, R., Kerr, A. R. W., and Schirmer, E. C.  (2017)  Tissue-specific NETs alter genome organization and regulation even in a heterologous system. Nucleus 8(1), 81-97. PMID: 28045568

*De Castro, I. J., Budzak, J., Di Giacinto, M. L., Ligammari, L., Gokhan, E., Spanos, C., Moralli, D., de las Heras, J. I., Schirmer, E. C., Ullman, K., Bickmore, W., Green, K., Rappsilber, J., Lamble, S., Goldberg, M. W., Vinciotii, V., and Vagnarelli, P.  (2017)  Repo-Man/PP1 regulates heterochromatin formation in interphase. Nat. Commun. 8, 14048. PMID: 28091603

Mudumbi, K. C., Schirmer, E. C., and Yang, W.  (2016)  Single-point single-molecule FRAP distinguishes inner and outer nuclear membrane protein distribution. Nat. Commun. 7, 12562. PMID: 27558844

*,F, GS50Robson, M. I., de las Heras, J. I., Czapiewski, R., Le Thanh, P., Booth, D. G., Kelly, D. A., Webb, S., Kerr, A. R. W., and Schirmer, E. C.  (2016)  Tissue-specific gene repositioning by muscle nuclear membrane proteins enhances repression of critical developmental genes during myogenesis. Mol. Cell 62(6), 834-847. PMID: 27264872

Batrakou, D. G., de las Heras, J. I., Czapiewski, R., Mouras, R., and Schirmer, E. C.  (2015)  TMEM120A and B: Nuclear envelope transmembrane proteins important for adipocyte differentiation. PLoS One 10(5):e0127712. PMID: 26024229

GS50Agirre, X., Castellano, G., Pascual, M., Heath, S., Kulis, M., Segura, V., Bergmann, A., Esteve, A., Merkel, A., Raineri, E., Agueda, L., Blanc, J., Richardson, D., Clarke, L., Russiñol, N., Queirós, A. C., Beekman, R., Rodriguez-Madoz, J. R., José-Enériz, E. S., Fang, F., Gutiérrez, N. C., García-Verdugo, J. M., Robson, M. I., Schirmer, E. C., Guruceaga, E., Martens, J., Gut, M., Calasanz, M. J., Flicek, P., Siebert, R., Campo, E., San Miguel, J. F., Melnick, A., Stunnenberg, H., Gut, I. G., Prosper, F., and Martin-Subero, J. I. (2015) Whole-genome epigenomic analysis in multiple myeloma reveals DNA hypermethylation of B-cell specific enhancers. Genome Res. Pii: gr180240.114. PMID: 25644835

Meinke, P., Schneiderat, P., Srsen, V., Korfali, N., Le Thanh, P., Cowan, G., Cavanagh, D. R., Wehnert, M., Schirmer, E. C.**, and Walter, M. C.**  (2015)  Abnormal proliferation and spontaneous differentiation of myoblasts from a symptomatic female carrier of X-linked Emery-Dreifuss muscular dystrophy. Neuromuscul. Disord. 25, 127-136. PMID: 25454731 Note: Commentary by Glenn E. Morris Neuromuscul. Disord. 25, 137.  **Corresponding authors.

Malik, P., Zuleger, N., de las Heras, J. I., Ros, N., Makarov, A. A., Lazou, V., Meinke, P., Waterfall, M., Kelly, D. A., and Schirmer, E. C.  (2014) NET23/STING promotes chromatin compaction from the nuclear envelope. PLoS One 9(11), e111851. PMID: 25386906

GS50Zuleger, N., Boyle, S., Kelly, D. A., de las Heras, J., Lazou, V., Korfali, N., Batrakou, D. G., Randles, K. N., Morris, G. E., Harrison, D. J., Bickmore, W. A., and Schirmer, E. C.  (2013) Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery. Genome Biol. 14(2), R14. PMID: 23414781

*,GS100Korfali, N., Wilkie, G. S., Swanson, S. K., Srsen, V., de las Heras, J., Batrakou, D. G., Malik, P., Zuleger, N., Kerr, A. R. W., Florens, L., and Schirmer, E. C.  (2012) The nuclear envelope proteome differs notably between tissues.  Nucleus 3(6), 552-564. PMID: 22990521

Malik, P., Tabarraei, A., Kehlenbach, R. H., Korfali, N., Iwasawa, R., Graham, S. V., and Schirmer, E. C. (2012)  Herpes simplex virus ICP27 protein directly interacts with the nuclear pore complex through Nup62, inhibiting host nucleocytoplasmic transport pathways.  J. Biol. Chem. 287(15), 12277-12292. PMID: 22334672

Kerr, A. R. W. and Schirmer, E. C.  (2011)  FG repeats facilitate integral protein trafficking to the inner nuclear membrane.  Commun. Integr. Biol. 4, 557-559. PMID: 22046461

Korfali, N., Srsen, V., Waterfall, M., Batrakou, D. G., Pekovic, V., Hutchison, C. J., and Schirmer, E. C.  (2011)  A flow cytometry-based screen of nuclear envelope transmembrane proteins identifies NET4/Tmem53 as involved in stress-dependent cell cycle withdrawal.  PLoS ONE 6(4), e18762. PMID: 21533191

F,C,GS50Zuleger, N., Kelly, D. A., Richardson, A. C., Kerr, A. R. W., Goldberg, M. W., Goryachev, A. B., and Schirmer, E. C.  (2011)  System analysis shows distinct mechanisms and common principles of nuclear envelope protein dynamics.  J. Cell Biol. 193, 109-123. PMID: 21444689

GS100Wilkie, G. S., Korfali, N., Swanson, S. K., Malik, P., Srsen, V., Batrakou, D. G., de las Heras, J., Zuleger, N., Kerr, A. R. W., Florens, L., and Schirmer, E. C.  (2011) Several novel nuclear envelope proteins from muscle have cytoskeletal associations.  Mol.  Cell.  Proteomics 10, M110.003129. PMID: 20876400

GS100Korfali, N., Wilkie, G.  S., Swanson, S.  K., Srsen, V., Batrakou, D.  G., Fairley, E.  A.  L., Malik, P., Zuleger, N., Goncharevich A., de las Heras, J., Kelly, D.  A., Kerr, A.  R.  W., Florens, L., and Schirmer, E.  C.  (2010) The leukocyte nuclear envelope proteome varies with cell activation and contains novel transmembrane proteins that affect genome architecture.  Mol.  Cell.  Proteomics 9, 2571-2585. PMID: 20693407

Malik, P., Korfali, N., Srsen, V., Lazou, V., Batrakou, D. G., Zuleger, N., Kavanagh, D. M., Wilkie, G. S., Goldberg, M. W., and Schirmer, E. C.  (2010) Cell-specific and lamin-dependent targeting of novel transmembrane proteins in the nuclear envelope.  Cell. Mol. Life Sci. 67, 1353-1369. PMID: 20091084

Ostlund, C., Guan, T., Figlewicz, D. A., Hays, A. P., Worman, H. J., Gerace, L., and Schirmer, E. C.  (2009) Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation.  Biochem. Biophys. Res. Commun. 389, 279-283. PMID: 19716805

Tunnah, D., Sewry, C. A., Vaux, D., Schirmer, E. C., and Morris, G. E.  (2005) The apparent absence of lamin B1 and emerin in many tissue nuclei is due to epitope masking.  J. Mol. Histol. 36(5), 337-344.  PMID: 16283426

F,GS100Ohba, T., Schirmer, E. C., Nishimoto, T., and Gerace, L.  (2004) Energy and temperature-dependent transport of integral proteins to the inner nuclear membrane via the nuclear pore. J. Cell Biol. 167, 1051-1062.

GS50Schirmer, E. C., and Gerace, L. (2004) The stability of the nuclear lamina polymer changes with the composition of lamin subtypes according to their individual binding strengths. J. Biol. Chem. 279, 42811-42817.  Epub 2004 Jul 27.

GS100Schirmer, E. C., Hohmann, O. A., Kowal, A. S., Lindquist, S. L.  (2004) Dominant gain-of-function mutations in Hsp104p reveal crucial roles for the middle region. Mol. Biol. Cell 15, 2061-2072.  Epub 2004 Feb 20.

*,F,GS500Schirmer, E. C., Florens, L., Guan, T. Yates, J. R. III, and Gerace, L. (2003) Nuclear membrane proteins with potential disease links found by subtractive proteomics. Science 301, 1380-1382.

GS100Cashikar, A. G., Schirmer, E. C., Hattendorf, D. A., Glover, J. R., Ramakrishnan, M. S., Ware, D. M., and Lindquist, S. L.  (2002) Defining a pathway of communication from the C-terminal peptide binding domain to the N-terminal ATPase domain in a AAA protein. Mol. Cell 9, 751-760.

GS100Schirmer, E. C., Guan, T., and Gerace, L.  (2001) Involvement of the lamin rod domain in heterotypic lamin interactions important for nuclear organization. J. Cell Biol. 153, 479-489.

GS50Schirmer, E. C., Queitsch, C., Ware, D. M., Kowal, A. S., and Lindquist, S.  (2001) Subunit interactions influence the biochemical and biological properties of Hsp104.  Proc. Natl. Acad. Sci. USA 98, 914-919.

GS100Guan, T., Kehlenbach, R. H., Schirmer, E. C., Kehlenbach, A., Fan, F., Clurman, B. E., Arnheim, N., and Gerace, L. (2000) Nup50, a nucleoplasmically oriented nucleoporin with a role in nuclear protein export. Mol. Cell. Biol. 15, 5619-5630.

GS100Saphire, A. C. S., Guan, T., Schirmer, E. C., Nemerow, G. R., and Gerace, L.  (2000)  Nuclear import of adenovirus DNA in vitro involves the nuclear protein import pathway and Hsc70.  J. Biol. Chem. 275, 4298-4304.

GS100Schirmer, E. C., Queitsch, C., Kowal, A. S., Parsell, D. A., Lindquist, S. (1998)  The ATPase activity of Hsp104: effects of environmental conditions and mutations.  J. Biol. Chem. 273, 15546-15552.

*,GS100Schirmer, E. C. and Lindquist, S.  (1997)  Interactions of the chaperone Hsp104 with yeast Sup35 and mammalian PrP.  Proc. Natl. Acad. Sci. USA 94, 13932-13937.  Subject of News and Views: Nature 392, 23-24 by W. J. Welch and P. Gambetti.

*,GS500Glover, J. R., Kowal, A. S., Schirmer, E. C., Patino, M. M., Liu, J. J., Lindquist, S.  (1997)  Self-seeded fibers formed by Sup35, the protein determinant of [PSI+], a heritable prion-like factor of S. cerevisiae.  Cell  89, 811-819.  Subject of News and Views: Nature 388, 228-229 by C. L. Masters and K. Beyreuther.

GS100Katsafanas, G. C., Schirmer, E. C., Wyatt, L. S., Frenkel, N.  (1996)  In vitro activation of Human herpesviruses 6 and 7 from latency.  Proc. Natl. Acad. Sci. USA  93, 9788-9792.

$,GS100Schirmer, E. C., Lindquist, S., Vierling, E.  (1994)  An Arabidopsis heat shock protein complements a thermotolerance defect in  yeast.  Plant Cell  6, 1899-1909.

$Schirmer, E. C., Farooqui, J., Polak, P. E., Szuchet, S.  (1994)  GRASP: A novel heparin-binding serum glycoprotein that mediates oligodendrocyte-substratum adhesion.  J. Neurosci. Res. 39, 457-473.

GS100Schirmer, E. C., Wyatt, L. S., Yamanishi, K., Rodriguez, W. J., Frenkel, N.  (1991)  Differentiation between two distinct classes of viruses now classified as human herpesvirus 6.  Proc. Natl. Acad. Sci. USA  88, 5922-5926.  This paper initiated a formal reconsideration and change in the nomenclature for Human Herpesvirus 6 strains.  Arch. Virol. 129, 363-366.

GS50Frenkel, N., Schirmer, E. C., Katsafanas, G., June, C. H.  (1990)  T-cell activation is required for efficient replication of human herpesvirus-6.  J. Virol. 64, 4598-4602.

GS50Di Luca, D.,  Katsafanas, G.,  Schirmer, E. C., Balachandran, N., Frenkel, N.  (1990)  The replication of viral and cellular DNA in human herpesvirus 6 infected cells.  Virol. 175, 199-210.

$,*,GS500Frenkel, N., Schirmer, E. C., Wyatt, L. S., Katsafanas, G., Roffman, E., Danovich, R., June, C. H.  (1990)  Isolation of a new herpesvirus from human CD4+ T cells.  Proc. Natl. Acad. Sci. USA  87, 748-752.

Invited Research Reports

Robson, M. I. and Schirmer, E. C.  (2016)  The application of DamID to identify peripheral gene sequences in differentiated and primary cells.  Methods Mol Biol. 1411, 359-386. PMID: 27147054

Korfali, N., Florens, L., and Schirmer, E. C.  (2016)  Isolation, proteomic analysis and microscopy confirmation of the liver nuclear envelope proteome.  Methods Mol Biol. 1411, 3-44. PMID: 27147032

Makarov, A. A., Rizzotto, A., Meinke, P., and Schirmer, E. C.  (2016)  Purification of lamins and soluble fragments of NETs.  Methods Enzymol. 569, 79-100. PMID: 26778554

Zuleger, N., Kelly, D. A., and Schirmer, E. C.  (2013)  Considering discrete proteins pools when measuring the dynamics of nuclear membrane proteins.  Methods Mol Biol. 1042, 275-298. PMID: 23980015

Korfali, N., Fairley, E. A. L., Swanson, S. K., Florens, L., and Schirmer, E. C.  (2009)  Use of sequential chemical extractions to purify nuclear membrane proteins for proteomics identification.  Methods Mol Biol. 528, 201-225. PMID: 19153695

Wilkie, G. S., and Schirmer, E. C.  (2008)  Purification of nuclei and preparation of nuclear envelopes from skeletal muscle.  Methods Mol Biol. 463, 23-41. PMID: 18951158

Florens, L., Korfali, N., and Schirmer, E. C.  (2008)  Subcellular Fractionation and Proteomics of Nuclear Envelopes.  Methods Mol Biol. 432, 117-137. PMID: 18370014

Lindquist, S., DebBurman, S. K., Glover, J. R., Kowal, A. S., Liu, J. J., Schirmer, E. C., and Serio, T. R.  (1998)  Amyloid fibres of Sup35 support a prion-like mechanism of inheritance in yeast.  Biochem. Soc. Trans. 26, 486-490.

Schirmer, E. C. and Lindquist, S.  (1998)  Purification and properties of Hsp104 from yeast.  Methods Enzymol. 290, 430-444.

Frenkel, N.,  Roffman, E., Schirmer, E. C., Katsafanas, G., Wyatt, L. S., June, C. H.  (1990)  Cellular and growth-factor requirements for the replication of human herpesvirus 6 in primary lymphocyte cultures.  Adv. Expt. Med. and Biol. 278, 1-8.

Refereed Review Articles

Tingey, M., Mudumbi, K. C., Schirmer E. C., and Yang, W. (2019) Casting a wider net: differentiation between inner nuclear envelope and outer nuclear envelope transmembrane proteins. Int. J. Mol. Sci. 20(21) pii: E5248. doi: 10.3390/ijms20215248. PMID: 31652379

Sivakumar, A., de las Heras, J. I., and Schirmer, E. C.  (2019) Spatial genome organization: from development to disease. Front. Genet. 7:18 doi 10.3389/fcell.2019.00018. PMID: 30949476

DORA statement: This review covers much of what is known about spatial genome organization in embryonic stem cells and early development and how it can go awry in human disease. As is typically the case for review articles from my lab, we also performed a bioinformatics analysis to add some new data, this time on the evolutionary conservation of architectural proteins involved in 3D spatial genome organization.

Meinke, P., and Schirmer, E. C.  (2016) The increasing relevance of nuclear envelope myopathies. Curr. Opin. Neurol. Jul 6. PMID: 27389815

Czapiewski, R., Robson, M. I., and Schirmer, E. C.  (2016) Anchoring a leviathan: how the nuclear membrane tethers the genome. Front. Genet. 7:82, doi: 10.3389/fgene.2016.00082. PMID: 27200088

Zhdanov, R., Schirmer, E. C., Venkatasubramani, A. V., Kerr, A. R. W., Mandrou, E., Rodriguez-Blanco, G., and Kagansky, A.  (2015) A subset of cellular lipids may provide a new dimension of epigenetic regulation through control over the structure and functions of chromatin. Science Open https://www.scienceopen.com/document_file/10c602eb-4360-45f9-9d38-2a10201bfd20/ScienceOpen/Lipids_in_Epigenetics_Review.pdf

GS50Worman H. J., and Schirmer, E. C.  (2015) Nuclear membrane diversity: underlying tissue-specific pathologies in disease? Curr. Opin. Cell Biol. 34. 101-112. PMID: 26115475

Meinke, P., and Schirmer, E. C.  (2015) LINC’ing form and function at the nuclear envelope. FEBS Lett. pii: S0014-5793(15)00468-8. PMID: 26096784

F,GS50de las Heras, J. I., Meinke, P., Batrakou, D. G. Srsen, V., Zuleger, N., Kerr, A. R. W., and Schirmer, E. C.  (2013) Tissue specificity in the nuclear envelope supports its functional complexity. Nucleus 4(6). 460-477. PMID: 24213376

CZuleger, N., Kerr, A. R. W., and Schirmer, E. C.  (2012) Many mechanisms, one entrance: membrane protein translocation into the nucleus. Cell. Mol. Life Sci. 69(13), 2205-2216. PMID: 22327555

GS50de las Heras, J. I., Batrakou, D. G., and Schirmer, E. C.  (2013) Cancer biology and the nuclear envelope: a convoluted relationship.  Sem. Cancer Biol. 23, 125-137. PMID: 22311402

GS50Zuleger, N., Robson, M. I., and Schirmer, E. C.  (2011) The nuclear envelope as a chromatin organizer.  Nucleus 2, 339-349. PMID: 21970986

Batrakou, D. G., Kerr, A. R. W., and Schirmer, E. C.  (2009) Comparative proteomic analyses of the nuclear envelope and pore complex suggests a wide range of heretofore unexpected functions.  J. Proteomics. 72, 56-70. PMID: 18852071

Schirmer, E. C.  (2008) The Epigenetics of nuclear envelope organization and disease.  Mutat. Res. 647, 112-121. PMID: 18722388

GS100Schirmer, E. C. and Foisner, R.  (2007) Proteins that associate with lamins: many faces, many functions.  Exp. Cell. Rsch. 313, 2167-2179. PMID: 17451680

Wilkie, G. S. and Schirmer, E. C.  (2006) Guilt by association: the nuclear envelope proteome and disease.  Mol. Cell. Proteomics 5, 1865-1875.  PMID: 16790741

GS100Schirmer, E. C. and Gerace, L. (2005)  The Nuclear Envelope Proteome: Extending the Envelope.  Trends Biochem. Sci. 30(10), 551-558. PMID: 16125387

Schirmer, E. C., Yates, J. R. III, and Gerace, L.  (Oct. 2003)  MudPIT: A powerful proteomics tool for discovery.  Discovery Medicine 3(18), 38-39.

Schirmer, E. C., and Gerace, L.  (2002)  Organellar proteomics: the prizes and pitfalls of opening the nuclear envelope. Genome Biology 3, 1008.1-1008.4.

GS500Schirmer, E. C., Glover, J. R., Singer, M. A., Lindquist, S.  (1996)  HSP100/ Clp proteins: a common mechanism explains diverse functions.  Trends Biochem. Sci.  21, 289-296.

Book Chapters and Invited Reviews

Dixon, C. R. and Schirmer, E. C. (2018) Navigating the nuclear envelope: one or multiple transport mechanisms for integral membrane proteins? In Nuclear-cytoplasmic transport from Springer Nucleic Acids and Molecular Biology series Vol 33, ed. Maximillian D'Angelo. Springer, chpt. 7 (pp 151-178). ISBN 978-3-319-77308-7.

Robson, M. I., Rizzotto, A., and Schirmer, E. C. (2018) Spatial organization of the nucleus compartmentalizes and regulates the genome. In Nuclear pore complexes in genome organization, function and maintenance, ed. Maximillian D'Angelo. Springer, chpt. 1 (pp 1-34). ISBN 978-3-319-71612-1.

Rizzotto, A. and Schirmer, E. C. (2017) Breaking the scale: how disrupting the karyoplasmic ratio gives cancer cells an advantage for metastatic invasion.  Biochem. Soc. Trans.  45(6), 1333-1344. PMID 29150524.

Meinke, P., Makarov, A. A., Le Thanh, P., Sadurska, D., and Schirmer, E. C. (2015) Nucleoskeleton dynamics and functions in health and disease.  Cell Health and Cytoskeleton  7, 55-69.

Stancheva, I., and Schirmer, E. C. (2014) Nuclear envelope: connecting structural genome organization to regulation of gene expression.  Adv. Exp. Med. Biol.  773, 209-244. PMID: 24563350

Robson, M. I., Le Thanh, P., and Schirmer, E. C. (2014) NETs and cell cycle regulation.  Adv. Exp. Med. Biol.  773, 165-185. PMID: 24563348

de las Heras, J. I., and Schirmer, E. C. (2014) The nuclear envelope and cancer: a diagnostic perspective and historical overview.  Adv. Exp. Med. Biol.  773, 5-26. PMID: 24563341

Srsen, V., Korfali, N., and Schirmer, E. C. (2011) Nuclear envelope influences on cell cycle progression.  Biochem. Soc. Trans.  39, 1742-1746. PMID: 22103518

Zuleger, N. and Schirmer, E. C.  (2011) The nuclear lamina as a chromatin organizer. In Genome organization and function in the cell nucleus, ed Karsten Rippe. Wiley, chpt. 8 (pp 185-209). ISBN 978-3-527-32698-3 and 64000-3.

Malik, P., Zuleger, N., and Schirmer, E. C. (2010) Nuclear envelope influences on genome organization.  Biochem. Soc. Trans.  38, 268-272. PMID: 20074072

Malik, P., Zuleger, N., and Schirmer, E. C.  (2009)  Transport of inner nuclear membrane proteins.  In Nuclear Transport, ed Ralph Kehlenbach, Landes Bioscience http://www.landesbioscience.com/curie/chapter/4204/.

Zuleger, N., Korfali, N., and Schirmer, E. C.  (2008)  Inner nuclear membrane protein transport is mediated by multiple mechanisms.  Biochem. Soc. Trans. 36, 1373-1377. PMID: 19021558

Kavanagh, D. M., Powell, W. E., Malik, P., Lazou, V., and Schirmer, E. C. (2007) Organelle Proteome Variation Among Different Cell Types: Lessons from Nuclear Membrane Proteins.  Subcell. Biochem. 43, 51-76. PMID: 17953391

Malik, P. and Schirmer, E. C.  (2006)  The Kaposi’s sarcoma-associated herpesvirus ORF57 protein: a pleurotropic regulator of gene expression.  Biochem. Soc. Trans. 34, 705-710. PMID: 17052179

Schirmer, E. C., Florens, L., Guan, T., Yates, J. R. III, and Gerace, L. (2005)  Identification of Novel Integral Membrane Proteins of the  Nuclear Envelope with Potential Disease Links Using Subtractive Proteomics in Novartis Foundation Symposium No. 264 Nuclear Organization in Development and Disease, J. Goode, ed. pp 63-76; discussion pp 76-80, 227-230.

Lindquist, S. and Schirmer, E. C.  (1999)  The Role of Hsp104 in Stress Tolerance and Prion Maintenance in Molecular Chaperones and Folding Catalysts: Regulation, Cellular Function and Mechanisms, B. Bukau,  ed. Harwood Academic Publishers, chpt. 17, pp 347-380.  ISBN 90-5702-370-9.

Schirmer, E. C., and Lindquist, S.  (1997)  The HSP100 family — an overview and Saccharomyces cerevisiae Hsp104 in Guidebook to Molecular Chaperones and Protein-Folding Catalysts.  M.-J. Gething (ed.). Sambrook & Tooze at Oxford University Press, pp. 231-236 and 249-251.  ISBN 0 19 859948 X and 0 19 859949 8.

Glover, J. R., Schirmer, E. C., Singer, M. A., Lindquist, S.  (1997)  Hsp104 in Molecular Chaperones in the Life Cycle of Proteins: Structure, Function, and Mode of Action.  A. L. Fink and Y. Goto (eds.).  Marcel Dekker Inc., chpt. 9 (pp 193-224).  ISBN 0-8247-0100-3.

Other Publications (1)

Schirmer, E.  (1997)  Stimulated Yeast.  Annals of Improbable Research  3 (5), 22.

A summary table of the nuclear envelope proteomics datasets we have generated can be accessed here: NE Proteomics Blood Liver Muscle (Excel 19.71MB)

 

Summary of tested NETs experimentally confirmed for nuclear envelope targeting can be accessed here: Net Targeting (Excel 50KB)

 

Gene expression and DamID datasets associated with our publications have all been submitted to the GEO short read sequence repository at NCBI.  The papers and links are given below.

 

Robson, M. I., et al.  (2016)  Tissue-specific gene repositioning by muscle nuclear membrane proteins enhances repression of critical developmental genes during myogenesis. Mol. Cell 62(6), 834-847. PMID: 27264872

 

LaminB1 DamID in undifferentiated mouse C2C12 myoblasts (ATCC, Lot 59501261) and differentiated C2C12 myotubes

DamID - C2C12 differentiation 4 samples

GSE80328

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80328

 

Transcriptome analysis of differentiating C2C12 mouse myoblasts (ATCC, Lot 59501261) with knock-down of NET39, TMEM38A, TMEM214 and WFS1.

Microarray - C2C12 differentiation with NET knockdowns 21 samples

GSE80329

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80329

 

Establishment of tissue-specific genome organisation by muscle-specific nuclear envelope transmembrane proteins (NETs) during mouse C2C12 myoblast differentiation

combined expression + genome organisation C2C12 differentiation with NET knockdowns 25 samples

GSE80330

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80330

 

de las Heras, J. I., et al.  (2017)  Tissue-specific NETs alter genome organization and regulation even in a heterologous system. Nucleus 8(1), 81-97. PMID: 28045568

 

LaminB1 DamID in HT1080 fibroblasts overexpressing NET29/TMEM120A, NET39/PPAPDC3 or NET47/TM7SF2

DamID - HT1080 with NET overexpression 8 samples

GSE87148

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87148

 

Transcriptome analysis of human HT1080 cells overexpressing full length or soluble nucleoplasmic fragment of NET29/TMEM120A, NET39/PPAPDC3 and NET47/TM7SF2

Microarray - HT1080 with NET overexpression 27 samples

GSE87150

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87150

 

Transcriptional and genome organization changes in HT1080 cells after overexpression of tissue-specific nuclear transmembrane proteins (NETs)

combined expression + genome organisation HT1080 with NET overexpression 35 samples

GSE87228

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87228

 

Robson, M. I., et al. (2017)  Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments. Genome Res doi: 10.1101/gr.212308.116. PMID: 28424353

 

Transcriptome analysis of human T-cell Jurkat cell line in resting cells (t0) and at 8h, 24h and 48h post-activation using Raji B-cells conjugated with superantigen (SEE)

Microarray - Jurkat activation 12 samples

GSE94970

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94970

 

Changes in chromatin association with the nuclear periphery in resting and activated Jurkat T-cells [DamID-seq] 4 samples

DamID - Jurkat activation

GSE94971

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94971

 

Genome reorganisation and transcriptional changes during activation of the human T-cell line Jurkat

combined expression + genome organisation Jurkat activation 16 samples

GSE94972

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94972

 

In process:

 

Czapiewski, R. C. et al. Gene/miRNA locus mispositioning in Tmem120A-/- mice yields a lipodystrophic pathology. Submitted.

 

Transcriptome analysis of differentiating 3T3L1 mouse pre-adipocytes with knock-down of Tmem120a and Tmem120b

Microarray - 3T3L1 differentiation, with NET29 knockdown 11 samples

 

LaminB1-DamID analysis of differentiating 3T3L1 mouse pre-adipocytes with knock-down of Tmem120a and Tmem120b

DamID - 3T3L1 differentiation, with NET29 knockdown 8 samples

 

Genome reorganisation and transcriptional changes during differentiation of 3T3L1 preadipocytes, with NET29 knockdown

combined expression + genome organisation 3T3L1 differentiation with NET29 knockdowns 19 samples

 

Gatticchi, L. et al. TM7SF2 disruption alters radial gene positioning in mouse liver leading to metabolic defects and diabetes characteristics. Submitted.

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