Dr Freek van Eeden
School of Biosciences
Senior Lecturer
f.j.vaneeden@sheffield.ac.uk
+44 114 222 2348
+44 114 222 2348
C13, Firth Court
Full contact details
Dr Freek van Eeden
School of Biosciences
C13
Firth Court
Western Bank
Sheffield
S10 2TN
School of Biosciences
C13
Firth Court
Western Bank
Sheffield
S10 2TN
- Profile
-
- 2006- present: Senior Lecturer, University of Sheffield
- 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. Nüsslein-Volhard Lab. Max Planck Inst. für Entwicklungsbiologie, Tübingen, Germany
- 1986 - 1992 MSc. Wageningen Agricultural University, The Netherlands
- Research interests
-
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
- Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements. Nature Genetics, 54(7), 1037-1050. View this article in WRRO
- Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor. Proceedings of the National Academy of Sciences, 118(28). View this article in WRRO
- Identification of additional outer segment targeting signals in zebrafish rod opsin. Journal of Cell Science, 134(6). View this article in WRRO
- Tdp1 protects from topoisomerase 1–mediated chromosomal breaks in adult zebrafish but is dispensable during larval development. Science Advances, 7(5). View this article in WRRO
- Glucocorticoids promote Von Hippel Lindau degradation and Hif-1α stabilization. Proceedings of the National Academy of Sciences, 114(37), 9948-9953.
- Fin clipping and genotyping embryonic zebrafish at 3 days post-fertilization. BioTechniques, 62(1). View this article in WRRO
- Genome-wide mapping of Hif-1α binding sites in zebrafish. BMC Genomics, 16(1). View this article in WRRO
- A method for high-throughput PCR-based genotyping of larval zebrafish tail biopsies.. Biotechniques, 55(6), 314-316.
- Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling.. Cardiovasc Res, 100(2), 252-261. View this article in WRRO
- A systematic genome-wide analysis of zebrafish protein-coding gene function.. Nature, 496, 494-497. View this article in WRRO
- A zebrafish model to study and therapeutically manipulate hypoxia signaling in tumorigenesis.. Cancer Res, 72(16), 4017-4027.
- Activation of hypoxia-inducible factor-1α (Hif-1α) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model.. Blood, 118(3), 712-722.
- Mutations affecting somite formation and patterning in the zebrafish, Danio rerio.. Development, 123, 153-164.
All publications
Journal articles
- Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements. Nature Genetics, 54(7), 1037-1050. View this article in WRRO
- Homeostatic regulation of glucocorticoid receptor activity by hypoxia-inducible factor 1 : from physiology to clinic. Cells, 10(12). View this article in WRRO
- Thalassemia, a human blood disorder. Brazilian Journal of Biology, 83. View this article in WRRO
- Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor. Proceedings of the National Academy of Sciences, 118(28). View this article in WRRO
- Zebrafish as a tractable model of human cardiovascular disease. British Journal of Pharmacology. View this article in WRRO
- Identification of additional outer segment targeting signals in zebrafish rod opsin. Journal of Cell Science, 134(6). View this article in WRRO
- Tdp1 protects from topoisomerase 1–mediated chromosomal breaks in adult zebrafish but is dispensable during larval development. Science Advances, 7(5). View this article in WRRO
- Investigation of the role of VHL-HIF signaling in DNA repair and apoptosis in zebrafish. Oncotarget, 11(13), 1109-1130. View this article in WRRO
- Semaphorin 3F signaling actively retains neutrophils at sites of inflammation. Journal of Clinical Investigation. View this article in WRRO
- A high throughput zebrafish chemical screen reveals ALK5 and non-canonical androgen signalling as modulators of the pkd2−/− phenotype. Scientific Reports, 10(1). View this article in WRRO
- TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells. Nature Communications, 10(1). View this article in WRRO
- tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis. Nature Communications, 10. View this article in WRRO
- The Zebrafish as an Emerging Model to Study DNA Damage in Aging, Cancer and Other Diseases. Frontiers in Cell and Developmental Biology, 6. View this article in WRRO
- The von Hippel-Lindau Gene Is Required to Maintain Renal Proximal Tubule and Glomerulus Integrity in Zebrafish Larvae. Nephron, 138(4), 310-323. View this article in WRRO
- Hedgehog signalling acts upstream of Laminin alpha1 transcription in the zebrafish paraxial mesoderm. Matrix Biology, 62, 58-74. View this article in WRRO
- Nitric oxide interacts with monoamine oxidase to modulate aggression and anxiety-like behaviour. European Neuropsychopharmacology.
- Glucocorticoids promote Von Hippel Lindau degradation and Hif-1α stabilization. Proceedings of the National Academy of Sciences, 114(37), 9948-9953.
- The Power of Zebrafish in Personalised Medicine, 179-197.
- Fin clipping and genotyping embryonic zebrafish at 3 days post-fertilization. BioTechniques, 62(1). View this article in WRRO
- Euthanizing zebrafish legally in Europe. EMBO reports, 17(12), 1688-1689.
- Zebrafish as a model for von Hippel Lindau and hypoxia-inducible factor signaling. Methods in Cell Biology.
- The effect of macrophage depletion on hypoxia signalling induced angiogenesis in zebrafish. Atherosclerosis, 244, E8-E9.
- Genome-wide mapping of Hif-1α binding sites in zebrafish. BMC Genomics, 16(1). View this article in WRRO
- Exploring the HIFs, buts and maybes of hypoxia signalling in disease: lessons from zebrafish models. 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.
- The zebrafish as a model of vascular development and disease.. Prog Mol Biol Transl Sci, 124, 93-122.
- Zebrafish as a model of cardiac disease.. Prog Mol Biol Transl Sci, 124, 65-91.
- Positive and negative regulation of Gli activity by Kif7 in the zebrafish embryo.. PLoS Genet, 9(12), e1003955. View this article in WRRO
- Hypoxia inducible factor signaling modulates susceptibility to mycobacterial infection via a nitric oxide dependent mechanism.. PLoS Pathog, 9(12), e1003789. View this article in WRRO
- A method for high-throughput PCR-based genotyping of larval zebrafish tail biopsies.. Biotechniques, 55(6), 314-316.
- Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling.. Cardiovasc Res, 100(2), 252-261. View this article in WRRO
- Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases.. ACS Chem Biol, 8(7), 1488-1496.
- A systematic genome-wide analysis of zebrafish protein-coding gene function.. Nature, 496, 494-497. View this article in WRRO
- Mutations in LRRC50 predispose zebrafish and humans to seminomas.. PLoS Genet, 9(4), e1003384. View this article in WRRO
- Hypoxia-inducible factor 2α regulates key neutrophil functions in humans, mice and zebrafish. Blood, 123(3), 366-376.
- Hedgehog signaling via a calcitonin receptor-like receptor can induce arterial differentiation independently of VEGF signaling in zebrafish.. Blood, 120(2), 477-488. View this article in WRRO
- A zebrafish model to study and therapeutically manipulate hypoxia signaling in tumorigenesis.. 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.
- Maternal topoisomerase II alpha, not topoisomerase II beta, enables embryonic development of zebrafish top2a-/- mutants.. BMC Dev Biol, 11, 71. View this article in WRRO
- Targeted mutation of the talpid3 gene in zebrafish reveals its conserved requirement for ciliogenesis and Hedgehog signalling across the vertebrates.. Development, 138(22), 4969-4978.
- Activation of hypoxia-inducible factor-1α (Hif-1α) delays inflammation resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish inflammation model.. Blood, 118(3), 712-722.
- A Zebrafish Model Of Delayed Inflammation Resolution: Pharmacological And Genetic Activation Of The HIF1a Pathway. B36. AIRWAY IMMUNE MECHANISMS AND INFLAMMATION: ANIMAL MODELS.
- High-Throughput Target-Selected Gene Inactivation in Zebrafish. ZEBRAFISH: GENETICS, GENOMICS AND INFORMATICS, 3RD EDITION, 104, 121-127.
- A Zebrafish Model for VHL and Hypoxia Signaling, 105, 163-190.
- von Hippel-Lindau tumor suppressor mutants faithfully model pathological hypoxia-driven angiogenesis and vascular retinopathies in zebrafish. Development, 137(11), e1106-e1106.
- von Hippel-Lindau tumor suppressor mutants faithfully model pathological hypoxia-driven angiogenesis and vascular retinopathies in zebrafish.. Dis Model Mech, 3(5-6), 343-353.
- Repression of Hedgehog signalling is required for the acquisition of dorsolateral cell fates in the zebrafish otic vesicle.. Development, 137(8), 1361-1371.
- Gli2a protein localization reveals a role for Iguana/DZIP1 in primary ciliogenesis and a dependence of Hedgehog signal transduction on primary cilia in the zebrafish.. BMC Biol, 8, 65. View this article in WRRO
- Zebrafish mutants in the von Hippel-Lindau tumor suppressor display a hypoxic response and recapitulate key aspects of Chuvash polycythemia.. Blood, 113(25), 6449-6460.
- Hedgehog signaling plays a cell-autonomous role in maximizing cardiac developmental potential.. Development, 135(22), 3789-3799.
- LRRC50, a conserved ciliary protein implicated in polycystic kidney disease.. J Am Soc Nephrol, 19(6), 1128-1138.
- Genetic analysis of the two zebrafish patched homologues identifies novel roles for the hedgehog signaling pathway.. BMC Dev Biol, 8, 15. View this article in WRRO
- Abstract 1103: Integrin-linked Kinase and Laminin alpha 4 Mutations Cause Human Cardiomyopathy. Circulation, 116(suppl_16).
- Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells.. Circulation, 116(5), 515-525.
- Genetic variation in the zebrafish.. Genome Res, 16(4), 491-497.
- The zebrafish mutants dre, uki, and lep encode negative regulators of the hedgehog signaling pathway.. PLoS Genet, 1(2), e19. View this article in WRRO
- Zebrafish rx3 and mab21l2 are required during eye morphogenesis.. Dev Biol, 270(2), 336-349.
- Efficient target-selected mutagenesis in zebrafish.. Genome Res, 13(12), 2700-2707.
- The microRNA-producing enzyme Dicer1 is essential for zebrafish development.. Nat Genet, 35(3), 217-218.
- The Wnt/beta-catenin pathway regulates cardiac valve formation.. Nature, 425(6958), 633-637.
- Zebrafish embryos as a model host for the real time analysis of Salmonella typhimurium infections.. Cell Microbiol, 5(9), 601-611.
- Barentsz is essential for the posterior localization of oskar mRNA and colocalizes with it to the posterior pole.. J Cell Biol, 154(3), 511-523. View this article in WRRO
- Two distinct cell populations in the floor plate of the zebrafish are induced by different pathways.. Dev Biol, 219(2), 350-363.
- The polarisation of the anterior-posterior and dorsal-ventral axes during Drosophila oogenesis.. Curr Opin Genet Dev, 9(4), 396-404.
- Developmental mutant screens in the zebrafish.. Methods Cell Biol, 60, 21-41.
- Role of sonic hedgehog in branchiomotor neuron induction in zebrafish.. 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.
- Regulation of netrin-1a expression by hedgehog proteins.. Mol Cell Neurosci, 11(4), 194-205.
- Chapter 2 Developmental Mutant Screens in the Zebrafish, 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.
- 123 Neural degeneration mutants in the zebrafish, danio rerio. 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.
- Distribution and characterization of plasmid-related sequences in the chromosomal DNA of different thermophilic Methanobacterium strains.. Mol Gen Genet, 240(1), 81-91.
- Modular organization of related Archaeal plasmids encoding different restriction-modification systems in Methanobacterium thermoformicicum.. Nucleic Acids Res, 20(24), 6501-6507.
- Loss of Deacetylation Enzymes Hdac6 and Sirt2 Promotes Acetylation of Cytoplasmic Tubulin, but Suppresses Axonemal Acetylation in Zebrafish Cilia. Frontiers in Cell and Developmental Biology, 9.
- foxc1a and foxc1b differentially regulate angiogenesis from arteries and veins by modulating Vascular Endothelial Growth Factor signalling.
- Bidirectional crosstalk between hypoxia-inducible factor and glucocorticoid signalling in zebrafish larvae. PLOS Genetics, 16(5). View this article in WRRO
- klf2ash317 Mutant Zebrafish Do Not Recapitulate Morpholino-Induced Vascular and Haematopoietic Phenotypes. PLoS ONE, 10(10). View this article in WRRO
Chapters
- Transgenesis, mutagenesis, knockdown, and genetic colony management, Laboratory Fish in Biomedical Research (pp. 139-155). Elsevier
Conference proceedings papers
- Hypoxia signaling modulates neutrophil nitric oxide in a zebrafish tuberculosis model. EUROPEAN RESPIRATORY JOURNAL, Vol. 44
- BLOOD FLOW SUPPRESSES NOTCH SIGNALLING VIA DLL4 AND IS REQUIRED FOR ANGIOGENESIS IN RESPONSE TO HYPOXIC SIGNALLING. HEART, Vol. 99
- HYPOXIA-INDUCIBLE FACTOR 2 alpha REGULATES NEUTROPHILIC INFLAMMATION IN HUMANS, MICE AND ZEBRAFISH. THORAX, Vol. 67 (pp A1-A1)
- Factor inhibiting Hif (Fih) affects formation and functionality of blood vessels, under conditions of de-regulated Hif. VASCULAR PHARMACOLOGY, Vol. 56(5-6) (pp 355-356)
- PKD2 MUTANT ZEBRAFISH DISPLAY EXCESSIVE DEVELOPMENTAL ANGIOGENESIS. HEART, Vol. 97(20) (pp 12-12)
- ANGIOGENESIS IN RESPONSE TO UPREGULATED HYPOXIC SIGNALLING IS DEPENDENT ON HAEMODYNAMIC FLOW. HEART, Vol. 97 (pp A43-A43)
- Repression of Hedgehog signalling is required for the acquisition of dorsolateral cell fates in the zebrafish otic vesicle. MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S155-S155)
- A zebrafish model to characterize von Hippel-Lindau disease. MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S60-S61)
- Hedgehog signaling plays a cell-autonomous role in maximizing cardiac developmental potential. 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
- Integrated annotation and analysis of genomic features reveal new types of functional elements and large-scale epigenetic phenomena in the developing zebrafish, Cold Spring Harbor Laboratory.
- Asymmetric Hapln1a drives regionalised cardiac ECM expansion and promotes heart morphogenesis during zebrafish development, Cold Spring Harbor Laboratory.
- The investigation of the role of VHL-HIF signaling in DNA repair and apoptosis in zebrafish, Cold Spring Harbor Laboratory.
- Bidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae, Cold Spring Harbor Laboratory.
- Multiomic atlas with functional stratification and developmental dynamics of zebrafish cis-regulatory elements. Nature Genetics, 54(7), 1037-1050. View this article in WRRO
- 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 Tübingen (recently also Sheffield)
- 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