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Professor Georg A Holländer

Roles and subjects

Professorial Fellow in Developmental Medicine

Contact

Georg.hollander@paediatrics.ox.ac.uk

Professor Georg Hollander FMedSc is the Hoffmann and Action Medical Research Professor of Developmental Medicine and Head of the Department of Paediatrics, and Professorial Fellow in Developmental Medicine at Jesus College.

Academic Background

MD, University of Basel, Switzerland, FMedSc

Basel University Medical School, Switzerland (1977- 1984): training in Paediatrics and Paediatric Pulmonary Medicine at Harvard Medical School  and at Basel University Children’s Hospitals of Basel: training in Experimental Immunology at the Basel Institute for Immunology, Basel, Switzerland, and the Dana Farber Cancer Institute, Harvard Medical School, Boston, USA.

Undergraduate Teaching

Basic Immunology.

Postgraduate Teaching

T cell and developmental immunology: Primary Immunodeficiencies.

Research Interests

The molecular and cellular control of thymus development and function in health and disease.

Research Grants

Awarded July 2014: Wellcome Trust Strategic Award entitled ‘The Homunculus in our Thymus: A Cellular Genomics Approach’.

Recent Publications

  1. Barthlott T, Bosch AJ, Berkemeier C, Nogales-Cadenas R, Jeker LT, Keller MP, Pascual-Montano A, and  Holländer GA. A subpopulation of CD103(pos) ICOS(pos) Treg cells occurs at high frequency in lymphopenic mice and represents a lymph node specific differentiation stage. Eur J Immunol. 2015;45:1760-71.
  2.  Dertschnig S, Hauri-Hohl MM, Holländer GA, and Krenger W. Impaired thymic expression of tissue-restricted antigens licenses the de novo generation of autoreactive CD4+ T cells during murine acute GVHD. Blood. 2015;125:2720-3. *=shared senior authorship
  3. Salio M, Puleston DJ, Mathan TSM, Shepherd D, Stranks AJ, Adamopoulou E,  Veerapen N, Besra GS, Hollander GA, Simon AK and Cerundolo V. Essential role for autophagy during invariant NKT cell development. Proc Natl Acad Sci 2014 Dec 30;111(52):E5678-87. doi: 10.1073/pnas.1413935112
  4. Parkinson NJ, Roddis M, Ferneyhough B, Zhang G, Marsden AJ, Maslau S, Sanchez-Pearson Y, Barthlott T, Humphreys IR, Ladell K, Price DA, Ponting CP, Hollander GA, Fischer MD. Violation of the 12/23 rule of genomic V(D)J recombination is common in lymphocytes. Genome Res. 2014 Nov 3. pii: gr.179770.114
  5. Sansom SN, Shikama N, Zhanybekova S, Nusspaumer G, Macaulay IC, Deadman ME, Heger A, Ponting CP, Holländer GA. Population and single cell genomics reveal the Aire-dependency, relief from Polycomb silencing and distribution of self-antigen expression in thymic epithelia. Genome Res. 2014 Sep 15. pii: gr.171645.113. doi:10.1101/gr.171645.113
  6. Kumar L, Chou J, Yee CS, Borzutzky A, Vollmann EH, von Andrian UH, Park SY, Hollander GA, Manis JP, Poliani PL, Geha RS. Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function. J Exp Med. 2014 May 5;211(5):929-42. doi: 10.1084/jem.20131379.
  7. Hauri-Hohl M, Zuklys S, Holländer GA, Ziegler SF. A regulatory role for TGF?-signaling in the establishment and function of the thymic medulla. Nature Immunol. 2014 Jun; 15(6):554-61. doi: 10.1038/ni.286
  8. Mayer CE, Žuklys S, Zhanybekova S, Ohigashi I, Teh HY, Sansom SN, Shikama-Dorn N, Hafen K, Macaulay IC, Deadman ME, Ponting CP, Takahama Y, Holländer GA. Dynamic spatio-temporal contribution of single β5t+ cortical epithelial precursors to the thymus medulla. Eur J Immunol. 2016, 46:846-56
  9. Saldaña JI, Solanki A, Lau CI, Sahni H, Ross S, Furmanski AL, Ono M, Holländer G, Crompton T. Sonic Hedgehog regulates thymic epithelial cell differentiation. J Autoimmun. 2016, ;68:86-97
  10. Satoh R, Kakugawa K, Yasuda T, Yoshida H, Sibilia M, Katsura Y, Levi B, Abramson J, Koseki Y, Koseki H, van Ewijk W, Hollander GA, Kawamoto H. Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells. PLoS Genet. 2016, 12:e1005776.
  11. Ohigashi I, Zuklys S, Sakata M, Mayer CE, Hamazaki Y, Minato N, Hollander GA, Takahama Y.Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors. Cell Rep. 2015 13:1432-43.
  12. Simon AK, Hollander GA, McMichael A. Evolution of the immune system in humans from infancy to old age. Proc Biol Sci. 2015, 282:20143085.
  13. Dertschnig, S, Hauri-Hohl MM, Vollmer M, Holländer* GA, Krenger* W. Impaired thymic expression of tissue-restricted antigens licenses the de novo generation of autoreactive CD4+ T cells during murine acute GVHD. Blood 2015, [125:2720-3. *=shared senior authorship]
  14. Žuklys s, Handel A, Zhanybekova S, Govani F, Keller M, Maio S, Mayer CE, The HY, Hafen K, Gallone G, Barthlott T, Ponting CP and Holländer GA. Foxn1 regulates in postnatal thymic epithelial cells key target genes essential for T cell development. Nature Immunology; 2016 [forthcoming]
  15. Smith MJ, Reichenbach DK, Parker SL, Riddle MJ, Mitchell J, Osum KC, Mohtashami M, Stefanski HE, Fife BT, Bhandoola A, Hogquist KA, Holländer GA, Zúñiga-Pflücker JC, Tolar J, Blazar BR. T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction. JCI Insight. 2017 May 18;2(10). pii: 92056. doi: 10.1172/jci.insight.9205
  16. Smith AR, Rota IA, Maio S, Massaad MJ, Lund TC, Notarangelo LD, Holländer GA, Blazar BR. Cadherin 17 mutation associated with leaky severe combined immune deficiency is corrected by HSCT. Blood Adv. 2017 Oct 23;1(23):2083-2087. doi:10.1182/bloodadvances.2017010926.
  17. Jain R, Sheridan JM, Policheni A, Heinlein M, Gandolfo LC, Dewson G, Smyth GK, Sansom SN, Fu NY, Visvader JE, Holländer GA, Strasser A, Gray DHD. A critical epithelial survival axis regulated by MCL-1 maintains thymic function in mice. Blood. 2017 Dec 7;130(23):2504-2515. doi: 10.1182/blood-2017-03-771576. Epub 2017 Sep 29.
  18. Wu Q, Ferry QRV, Baeumler TA, Michaels YS, Vitsios DM, Habib O, Arnold R, Jiang X, Maio S, Steinkraus BR, Tapia M, Piazza P, Xu N, Holländer GA, Milne TA, Kim JS, Enright AJ, Bassett AR, Fulga TA. In situ functional dissection of RNA cis-regulatory elements by multiplex CRISPR-Cas9 genome engineering. Nat Commun. 2017 Dec 13;8(1):2109. doi: 10.1038/s41467-017-00686-2.
  19. Wendland K, Niss K, Kotarsky K, Wu NYH, White AJ, Jendholm J, Rivollier A, Izarzugaza JMG, Brunak S, Holländer GA, Anderson G, Sitnik KM, Agace WW.Retinoic Acid Signaling in Thymic Epithelial Cells Regulates Thymopoiesis. J Immunol. 2018 Jul 15;201(2):524-532. doi: 10.4049/jimmunol.1800418. Epub 2018 May 30. PMID: 29848752
  20. Stefanski HE, Xing Y, Taylor PA, Maio S, Henao-Meija J, Williams A, Flavell RA, Hollander GA, Blazar BR. Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development. PLoS One. 2018 Jun 27;13(6):e0198871. doi: 10.1371/journal.pone.0198871. eCollection 2018. PMID: 29949604
  21. Xing Y, Smith MJ, Goetz CA, McElmurry RT, Parker SL, Min D,Hollander, Weinberg KI, Tolar J, Stefanski HE, Blazar BR Thymic epithelial cell support of thymopoiesis does not require Klotho,” J Immunol. 2018 Dec 1;201(11):3320-3328. doi: 10.4049/jimmunol.1800670. Epub 2018 Oct 29.
  22. Handel AE, Shakama-Dorn N, Zhanybekova S, Maio S, Graedel AN, Žuklys S, Ponting CP and Hollander GA. Comprehensively profiling the chromatin architecture of tissue restricted antigen expression in thymic epithelial cells over development. Front Immunol. 2018 Sep 19;9:2120. doi: 10.3389/fimmu.2018.02120. eCollection 2018.
  23. Handel AE, Irani SR, Holländer GA. Grand Central: The role of central tolerance for induction of central nervous system autoimmunity. Nat Rev Neurol. 2018 Dec;14(12):723-734. doi: 10.1038/s41582-018-0095-7. Review.
  24. Fergusson JR, Morgan MD, Bruchard M, Huitema L, Heesters BA, van Unen V, van Hamburg JP, van der Wel NN, Picavet D, Koning F, Tas SW, Anderson MS, Marioni JC, Holländer GA, Spits H. Maturing Human CD127+ CCR7+ PDL1+ Dendritic Cells Express AIRE in the Absence of Tissue Restricted Antigens.Front Immunol. 2019 Jan 14;9:2902. doi: 10.3389/fimmu.2018.02902. eCollection 2018.
  25. Coles AJ, Azzopardi L, Kousin-Ezewu O, Mullay HK, Thompson SA, Jarvis L, Davies J, Howlett S, Rainbow D, Babar J, Sadler TJ, Brown JWL, Needham E, May K, Georgieva ZG, Handel AE, Maio S, Deadman M, Rota I, Holländer G, Dawson S, Jayne D, Seggewiss-Bernhardt R, Douek DC, Isaacs JD, Jones JL. Keratinocyte growth factor impairs human thymic recovery from lymphopenia. JCI Insight. 2019 May 7;5. pii: 125377. doi: 10.1172/jci.insight. 125377.
  26. Bortolomai I, Sandri M, Draghici E, Fontana E, Campodoni E, Marcovecchio GE, Ferrua F, Perani L, Spinelli A, Canu T, Catucci M, Di Tomaso T, Sergi LS, Esposito A, Lombardo A, Naldini L, Tampieri  A, Hollander GA, Villa A, Bosticardo M. Gene modification and 3D scaffolds as novel tools to allow the use of post-natal thymic epithelial cells for thymus regeneration approaches.Stem Cells Transl Med. 2019 Oct;8(10):1107-1122. doi: 10.1002/sctm.18-0218. Epub 2019 May 29.
  27. Dhalla F, Baran-Gale J, Maio S, Chappell L, Holländer GA, Ponting CP. Biologically indeterminate yet ordered promiscuous gene expression in single medullary thymic epithelial cells. EMBO J. 2019 Oct 28:e101828. doi: 10.15252/embj.2019101828.
  28. Handel AE, Holländer GA. Comment on “Identification of an Intronic Regulatory Element Necessary for Tissue-Specific Expression of Foxn1 in Thymic Epithelial Cells”. J Immunol. 2019 Nov 1;203(9):2355. doi: 10.4049/jimmunol.1900948.
  29. Newman JA, Aitkenhead H, Gavard AE, Rota IA, Handel AE,Hollander GA,Gileadi O.The crystal structure of human forkhead box N1 in complex with DNA reveals the structural basis for forkhead box family specificity. J Biol Chem. 2020 Mar 6;295(10):2948-2958. doi: 10.1074/jbc.RA119.010365. Epub 2019 Dec 30.PMID: 31914405

Other Information

In addition to his academic roles in Oxford, Georg is also the Director of the Botnar Research Centre for Child Health, BRCCH, where scientist jointly address essential challenges in global paediatric and adolescent health.

Hobbies

Travel, Films, Art

Links

Subject notes for courses taught at Jesus College:

See also Professor Holländer’s personal web page, the Department of Paediatrics website and the MRC Weatherall Institute of Molecular Medicine website.