Dr Freek van Eeden
School of Biosciences
Senior Lecturer
+44 114 222 2348
Full contact details
School of Biosciences
C13
Firth Court
Western Bank
葫芦影业
S10 2TN
- Profile
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- 2006- present: Senior Lecturer, University of 葫芦影业
- 1999 - 2005: Junior Group Leader Hubrecht Laboratory, Utrecht, The Netherlands
- 1997 - 1999: Post-doctoral worker, D. StJohnston Lab, Wellcome/CRC Inst. Cambridge UK
- 1992 - 1997: PhD, C. N眉sslein-Volhard Lab. Max Planck Inst. f眉r Entwicklungsbiologie, T眉bingen, Germany
- 1986 - 1992 MSc. Wageningen Agricultural University, The Netherlands
- Research interests
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Using the zebrafish as a genetic tool to study development and disease. We are interested in understanding the role of the patched genes in Hedgehog signaling. In addition, we have created a knockout for the von Hippel Lindau disease (VHL) gene and are interested in modeling VHL deficient cancers in zebrafish.
Understanding VHL and hypoxic signalling in Cancer
The zebrafish provides a powerful organism to model human development and disease. We are exploiting and developing the zebrafish, e.g. by creating such disease models, by using knockout technology like CRISPR, or by looking for chemicals that can modify disease-relevant phenotypes.
One of our current projects, models the human Von Hippel Lindau disease, caused by mutation of the VHL gene. VHL is a negative regulator of the Hypoxia Inducible Factor (HIF) signalling pathway, which is vital for development and survival of many tumours. However, this is not the only function of VHL and over the years numerous others have been identified. We found that in zebrafish, the functions of human VHL have been split over two genes, which we named vhl and vhl-like (vll).
Interestingly, we found that the fish vhl gene has an important role in HIF regulation, as mutants we made by reverse genetics show all hallmarks of an inappropriate hypoxic response under normoxic conditions. The role of vll was initially enigmatic, null mutants that we created in this gene were viable and fertile. However, using a unique and novel in vivo reporter for genome stability that we created, we discovered that the vll gene is important for maintaining genome stability, which is a major driver for tumour initiation. This is what we are currently trying to understand better.
Current collaborations: Sherif El-Khamisy (genome stability), Albert Ong (pkd2 model), Jane McKeating (Birmingham), Francesco Argenton (Padua) (both glucocorticoid-HIF interaction).
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- . Nature Genetics, 54(7), 1037-1050.
- . Proceedings of the National Academy of Sciences, 118(28).
- . Journal of Cell Science, 134(6).
- . Science Advances, 7(5).
- . Proceedings of the National Academy of Sciences, 114(37), 9948-9953.
- . BioTechniques, 62(1).
- . BMC Genomics, 16(1).
- . Biotechniques, 55(6), 314-316.
- . Cardiovasc Res, 100(2), 252-261.
- . Nature, 496, 494-497.
- . Cancer Res, 72(16), 4017-4027.
- . Blood, 118(3), 712-722.
- Mutations affecting somite formation and patterning in the zebrafish, Danio rerio.. Development, 123, 153-164.
All publications
Journal articles
- . Nature Genetics, 54(7), 1037-1050.
- . Cells, 10(12).
- . Brazilian Journal of Biology, 83.
- . Proceedings of the National Academy of Sciences, 118(28).
- . British Journal of Pharmacology.
- . Journal of Cell Science, 134(6).
- . Science Advances, 7(5).
- . Oncotarget, 11(13), 1109-1130.
- . Journal of Clinical Investigation.
- . Scientific Reports, 10(1).
- . Nature Communications, 10(1).
- . Nature Communications, 10.
- . Frontiers in Cell and Developmental Biology, 6.
- . Nephron, 138(4), 310-323.
- . Matrix Biology, 62, 58-74.
- . European Neuropsychopharmacology.
- . Proceedings of the National Academy of Sciences, 114(37), 9948-9953.
- , 179-197.
- . BioTechniques, 62(1).
- . EMBO reports, 17(12), 1688-1689.
- . Methods in Cell Biology.
- . Atherosclerosis, 244, E8-E9.
- . BMC Genomics, 16(1).
- . Disease Models & Mechanisms, 8(11), 1349-1360.
- Hypoxic signalling modulates neutrophil nitric oxide in a zebrafish tuberculosis model. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 44, 12-12.
- . Prog Mol Biol Transl Sci, 124, 93-122.
- . Prog Mol Biol Transl Sci, 124, 65-91.
- . PLoS Genet, 9(12), e1003955.
- . PLoS Pathog, 9(12), e1003789.
- . Biotechniques, 55(6), 314-316.
- . Cardiovasc Res, 100(2), 252-261.
- . ACS Chem Biol, 8(7), 1488-1496.
- . Nature, 496, 494-497.
- . PLoS Genet, 9(4), e1003384.
- . Blood, 123(3), 366-376.
- . Blood, 120(2), 477-488.
- . Cancer Res, 72(16), 4017-4027.
- A systematic genome-wide knockout generation and analysis of zebrafish protein-coding gene function.. MOLECULAR BIOLOGY OF THE CELL, 23.
- . BMC Dev Biol, 11, 71.
- . Development, 138(22), 4969-4978.
- . Blood, 118(3), 712-722.
- . B36. AIRWAY IMMUNE MECHANISMS AND INFLAMMATION: ANIMAL MODELS.
- . ZEBRAFISH: GENETICS, GENOMICS AND INFORMATICS, 3RD EDITION, 104, 121-127.
- , 105, 163-190.
- . Development, 137(11), e1106-e1106.
- . Dis Model Mech, 3(5-6), 343-353.
- . Development, 137(8), 1361-1371.
- . BMC Biol, 8, 65.
- . Blood, 113(25), 6449-6460.
- . Development, 135(22), 3789-3799.
- . J Am Soc Nephrol, 19(6), 1128-1138.
- . BMC Dev Biol, 8, 15.
- . Circulation, 116(suppl_16).
- . Circulation, 116(5), 515-525.
- . Genome Res, 16(4), 491-497.
- . PLoS Genet, 1(2), e19.
- . Dev Biol, 270(2), 336-349.
- . Genome Res, 13(12), 2700-2707.
- . Nat Genet, 35(3), 217-218.
- . Nature, 425(6958), 633-637.
- . Cell Microbiol, 5(9), 601-611.
- . J Cell Biol, 154(3), 511-523.
- . Dev Biol, 219(2), 350-363.
- . Curr Opin Genet Dev, 9(4), 396-404.
- . Methods Cell Biol, 60, 21-41.
- . Mech Dev, 76(1-2), 101-115.
- Sonic hedgehog is not required for the induction of medial floor plate cells in the zebrafish.. Development, 125(15), 2983-2993.
- . Mol Cell Neurosci, 11(4), 194-205.
- , 21-41.
- Zebrafish segmentation and pair-rule patterning.. Dev Genet, 23(1), 65-76.
- Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish.. Development, 124(21), 4373-4382.
- Genes controlling and mediating locomotion behavior of the zebrafish embryo and larva.. Development, 123, 399-413.
- Zebrafish mutations affecting retinotectal axon pathfinding.. Development, 123, 427-438.
- Jaw and branchial arch mutants in zebrafish I: branchial arches.. Development, 123, 329-344.
- Jaw and branchial arch mutants in zebrafish II: anterior arches and cartilage differentiation.. Development, 123, 345-356.
- Zebrafish pigmentation mutations and the processes of neural crest development.. Development, 123, 369-389.
- Mutations affecting xanthophore pigmentation in the zebrafish, Danio rerio.. Development, 123, 391-398.
- Genetic analysis of fin formation in the zebrafish, Danio rerio.. Development, 123, 255-262.
- Mutations affecting the cardiovascular system and other internal organs in zebrafish.. Development, 123, 293-302.
- Characterization of zebrafish mutants with defects in embryonic hematopoiesis.. Development, 123, 311-319.
- Mutations affecting neurogenesis and brain morphology in the zebrafish, Danio rerio.. Development, 123, 205-216.
- Neural degeneration mutants in the zebrafish, Danio rerio.. Development, 123, 229-239.
- Mutations affecting development of the zebrafish inner ear and lateral line.. Development, 123, 241-254.
- Mutations affecting somite formation and patterning in the zebrafish, Danio rerio.. Development, 123, 153-164.
- Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain.. Development, 123, 179-190.
- Genes involved in forebrain development in the zebrafish, Danio rerio.. Development, 123, 191-203.
- Mutations affecting the formation of the notochord in the zebrafish, Danio rerio.. Development, 123, 103-115.
- Mutations affecting development of the midline and general body shape during zebrafish embryogenesis.. Development, 123, 129-142.
- Mutations affecting morphogenesis during gastrulation and tail formation in the zebrafish, Danio rerio.. Development, 123, 143-151.
- The zebrafish early arrest mutants.. Development, 123, 57-66.
- Genes establishing dorsoventral pattern formation in the zebrafish embryo: the ventral specifying genes.. Development, 123, 81-93.
- dino and mercedes, two genes regulating dorsal development in the zebrafish embryo.. Development, 123, 95-102.
- The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio.. Development, 123, 1-36.
- The zebrafish epiboly mutants.. Development, 123, 47-55.
- . International Journal of Developmental Neuroscience, 14, 80-80.
- Mutations affecting pigmentation and shape of the adult zebrafish. Roux's Archives of Developmental Biology, 206(4), 260-276.
- no tail (ntl) is the zebrafish homologue of the mouse T (Brachyury) gene.. Development, 120(4), 1009-1015.
- . Mol Gen Genet, 240(1), 81-91.
- . Nucleic Acids Res, 20(24), 6501-6507.
- . Frontiers in Cell and Developmental Biology, 9.
- .
- . PLOS Genetics, 16(5).
- . PLoS ONE, 10(10).
Chapters
Conference proceedings papers
- Hypoxia signaling modulates neutrophil nitric oxide in a zebrafish tuberculosis model. EUROPEAN RESPIRATORY JOURNAL, Vol. 44
- . HEART, Vol. 99
- . THORAX, Vol. 67 (pp A1-A1)
- . VASCULAR PHARMACOLOGY, Vol. 56(5-6) (pp 355-356)
- . HEART, Vol. 97(20) (pp 12-12)
- . HEART, Vol. 97 (pp A43-A43)
- . MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S155-S155)
- . MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S60-S61)
- . DEVELOPMENTAL BIOLOGY, Vol. 319(2) (pp 603-604)
- Integrin-linked kinase and laminin alpha 4 mutations cause human cardiomyopathy. CIRCULATION, Vol. 116(16) (pp 221-221)
- Proper vascular development and heart morphogenesis require tumor suppressor VHL in zebrafish development.. CANCER RESEARCH, Vol. 66(8)
Preprints
- Grants
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- EU FP7
- EU Trancyst
- HEFCE
- Teaching activities
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Undergraduate:
- BMS109 Lab Skills & Skills Sessions
- BMS110 Research Topics in Biomedicine
- BMS242/243 Principles of Developmental Biology
- BMS243/247 Stem Cells
- BMS336 Modelling Human Disease and Dysfunction
- Level 3 Practical and Dissertation Modules
Masters (MSc):
- BMS6083 Practical Developmental Genetics (Co-ordinator)
- Professional activities and memberships
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- Invited teacher at regular EMBO courses at the MPI in T眉bingen (recently also 葫芦影业)
- Presenter at open science days and public lectures in Utrecht/Wageningen
- International collaboration on TILLING with Hubrecht Laboratory Utrecht/Sanger Inst. Cambridge
- Invited speaker at: ZDM8, Boston, Aug 2015; Zebrafish PI Meeting Ein gedi 2014; BSDB meeting 2013; European zebrafish meeting Barcelona 2013
- Reviewer for: BBSRC, Development, FNRS, Swiss research council, Singapore, Hong-Kong and many others