In our lab we take advantage of the transparency and genetic amenability of the zebrafish embryo to uncover the mechanisms controlling specification of lymphatic endothelial cells and assembly of lymphatic vessels (Yaniv, 2006). Recently, we have revealed the existence of a novel niche of specialized progenitors, which gives rise to the lymphatic system, and have identified the first “lymphatic-inducing” signal. Moreover, using this factor we have been able to induce lymphatic differentiation of human embryonic stem cells, allowing for the first time the generation of human lymphatic endothelial cells in culture (Nicenboim, 2015).
Current projects in the lab involve further understanding of lymphatic formation in the zebrafish embryo, as well as characterization of organ-specific lymphatic vessels. In particular, we are interested in understanding how do lymphatic vessels in the heart form, what are their origins, and what is their putative role during cardiac pathologies. Finally, since the lymphatic system represents the main route for dissemination of metastatic cells, we aim to understand the mechanisms underlying tumor-induced lymphangiogenesis (the formation of new lymphatic vessels), and whether or not they relate to the circuits controlling lymphatic formation during embryonic development.
Specialized angioblasts in the floor of the Cardinal Vein give rise to the lymphatic system
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“Tubing” the vertebrate’s body- Mechanisms of blood...
Mechanisms of blood vessel formation
In our lab we look at several aspects of blood vessel formation:
The link between lipids and angiogenesis: The interaction between endothelial cells (ECs) and lipoproteins (the particles carrying cholesterol and triglycerides through the blood) has direct relevance to atherosclerosis, thrombosis and cardiovascular disease. In order to study the effects of lipoproteins on blood vessel development and function, we use novel zebrafish models of hypo-, and hyper-lipidemia.
Taking advantage of these models, in combination with hyperlipidemic mice and cultured human endothelial cells we have been able to show that lipoproteins directly regulate developmental angiogenesis (Avraham-Davidi, 2012). Furthermore, we showed that the ApoB protein carried within LDL, and not the lipid components, plays a major role in triggering the vascular response, opening up a new set of questions regarding the effects of hyperlipidemia on the vasculature.
live imaging of LDL uptake by endothelial cells
The formation of organ-specific vessels: At present it is well accepted that vessels of a particular organ display specific features that enable them to fulfill distinct functions. For instance ECs in the brain, which generate the blood-brain barrier, are structurally different from ECs in the fenestrated capillaries of the kidney or liver. We use transgenic zebrafish expressing fluorescent reporters in different organs, in combination with long-term live imaging to study the mechanisms underlying the formation of organ-specific vessels. In addition, we have developed protocols for UV-mediated photoconversion of restricted populations of ECs, followed by FACS isolation and RNA-Seq analyses. Altogether these studies are expected to shed light on novel players specifically expressed in ECs of certain organs, and responsible for their distinct function.
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Angiogenesis related diseases
Tumor Angiogenesis and Lipid Metabolism
Based on our previous findings demonstrating that high lipid levels inhibit angiogenesis, we are currently extending the scope of our studies to tumor biology. We are especially interested in understanding how lipoprotein metabolism regulates the angiogenic process in tumors and how it affects metastasis formation. For that purpose we make use of zebrafish-, and mouse- models of hyperlipidemia in combination with flow cytometry and microscopy, which enable focusing on molecular events that occur specifically in the vessels located within the tumor bulk. The combination of multiple approaches and novel “viewpoints” will hopefully allow us to achieve a deep understanding of tumor angiogenesis and reveal new "weakpoints" in the ability of tumor to grow vessels.
Visualization of blood vessels in tumors via micro-CT. Perfusion of radiopaque cast allows 3D imaging and quantification of functional vasculature in cancer.
Vessel integrity and permeability
We use zebrafish to study vascularization of the CNS in normal and pathological conditions. Using transgenic and mutant zebrafish lines we characterize the mechanisms involved in pathological conditions manifested by impaired vessel integrity and permeability, such as cranial hemorrhage.
Zebrafish mutant with cranial hemorrhage
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The Yaniv Lab, focuses on understanding the mechanisms controlling blood and lymphatic vessel formation during embryonic development and pathological conditions. Above 20 million people die every year from CVDs, representing 30 percent of all global deaths. Today it is widely accepted that many of the genes activated during pathological angiogenesis and lymphangiogenesis are the same ones that play major roles in developmental vessel formation. Therefore, studies as those carried out in our laboratory have tremendous potential clinical relevance, and may unearth novel medically useful molecules.
In our lab we take advantage of the transparency and genetic amenability of the zebrafish embryo to uncover the mechanisms controlling specification of lymphatic endothelial cells and assembly of lymphatic vessels (Yaniv, 2006). Recently, we have revealed the existence of a novel niche of specialized progenitors, which gives rise to the lymphatic system, and have identified the first “lymphatic-inducing” signal. Moreover, using this factor we have been able to induce lymphatic differentiation of human embryonic stem cells, allowing for the first time the generation of human lymphatic endothelial cells in culture (Nicenboim, 2015).
Current projects in the lab involve further understanding of lymphatic formation in the zebrafish embryo, as well as characterization of organ-specific lymphatic vessels. In particular, we are interested in understanding how do lymphatic vessels in the heart form, what are their origins, and what is their putative role during cardiac pathologies. Finally, since the lymphatic system represents the main route for dissemination of metastatic cells, we aim to understand the mechanisms underlying tumor-induced lymphangiogenesis (the formation of new lymphatic vessels), and whether or not they relate to the circuits controlling lymphatic formation during embryonic development.
Specialized angioblasts in the floor of the Cardinal Vein give rise to the lymphatic system
Mechanisms of blood vessel formation
In our lab we look at several aspects of blood vessel formation:
The link between lipids and angiogenesis: The interaction between endothelial cells (ECs) and lipoproteins (the particles carrying cholesterol and triglycerides through the blood) has direct relevance to atherosclerosis, thrombosis and cardiovascular disease. In order to study the effects of lipoproteins on blood vessel development and function, we use novel zebrafish models of hypo-, and hyper-lipidemia.
Taking advantage of these models, in combination with hyperlipidemic mice and cultured human endothelial cells we have been able to show that lipoproteins directly regulate developmental angiogenesis (Avraham-Davidi, 2012). Furthermore, we showed that the ApoB protein carried within LDL, and not the lipid components, plays a major role in triggering the vascular response, opening up a new set of questions regarding the effects of hyperlipidemia on the vasculature.
live imaging of LDL uptake by endothelial cells
The formation of organ-specific vessels: At present it is well accepted that vessels of a particular organ display specific features that enable them to fulfill distinct functions. For instance ECs in the brain, which generate the blood-brain barrier, are structurally different from ECs in the fenestrated capillaries of the kidney or liver. We use transgenic zebrafish expressing fluorescent reporters in different organs, in combination with long-term live imaging to study the mechanisms underlying the formation of organ-specific vessels. In addition, we have developed protocols for UV-mediated photoconversion of restricted populations of ECs, followed by FACS isolation and RNA-Seq analyses. Altogether these studies are expected to shed light on novel players specifically expressed in ECs of certain organs, and responsible for their distinct function.
Tumor Angiogenesis and Lipid Metabolism
Based on our previous findings demonstrating that high lipid levels inhibit angiogenesis, we are currently extending the scope of our studies to tumor biology. We are especially interested in understanding how lipoprotein metabolism regulates the angiogenic process in tumors and how it affects metastasis formation. For that purpose we make use of zebrafish-, and mouse- models of hyperlipidemia in combination with flow cytometry and microscopy, which enable focusing on molecular events that occur specifically in the vessels located within the tumor bulk. The combination of multiple approaches and novel “viewpoints” will hopefully allow us to achieve a deep understanding of tumor angiogenesis and reveal new "weakpoints" in the ability of tumor to grow vessels.
Visualization of blood vessels in tumors via micro-CT. Perfusion of radiopaque cast allows 3D imaging and quantification of functional vasculature in cancer.
Vessel integrity and permeability
We use zebrafish to study vascularization of the CNS in normal and pathological conditions. Using transgenic and mutant zebrafish lines we characterize the mechanisms involved in pathological conditions manifested by impaired vessel integrity and permeability, such as cranial hemorrhage.
Zebrafish mutant with cranial hemorrhage
Publications
2019
2018
2017
2016
2015
2014
2013
2012
2011
2009
2007
2006
2019
Title
Journal
Authors
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Intercellular pathways from the vasculature to the forming bone in the zebrafish larval caudal fin: Possible role in bone formation
Journal of Structural Biology
Akiva A., Nelkenbaum O., Schertel A., Yaniv K., Weiner S. & Addadi L.
Transient p53-Mediated Regenerative Senescence in the Injured Heart
Circulation
Sarig R., Rimmer R., Bassat E., Zhang L., Umansky K. B., Lendengolts D., Perlmoter G., Yaniv K. & Tzahor E.
2018
Title
Journal
Authors
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Somatic NRAS mutation in patient with generalized lymphatic anomaly
Angiogenesis
Manevitz-Mendelson E., Leichner G. S., Barel O., Davidi-Avrahami I., Ziv-Strasser L., Eyal E., Pessach I., Rimon U., Barzilai A., Hirshberg A., Chechekes K., Amariglio N., Rechavi G., Yaniv K. & Greenberger S.
2017
Title
Journal
Authors
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Zebrafish skeleton development: High resolution micro-CT and FIB-SEM block surface serial imaging for phenotype identification
PLoS One
Silvent J., Akiva A., Brumfeld V., Reznikov N., Rechav K., Yaniv K., Addadi L. & Weiner S.
2016
Title
Journal
Authors
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A new role of hindbrain boundaries as pools of neural stem/progenitor cells regulated by Sox2
BMC Biology
Peretz Y., Eren N., Kohl A., Hen G., Yaniv K., Weisinger K. & Cinnamon Y.
The mid-developmental transition and the evolution of animal body plans
Nature
Levin M., Anavy L., Cole A., Winter E., Mostov N., Khair S., Senderovich N., Kovalev E., Silver D., Feder M., Fernandez-Valverde S., Nakanishi N., Simmons D., Simakov O., Larsson T., Liu S., Jerafi-Vider A., Yaniv K., Ryan J., Martindale M., Rink J., Arendt D., Degnan S., Degnan B., Hashimshony T. & Yanai I.
Development of the lymphatic system: new questions and paradigms
Development
Semo J., Nicenboim J. & Yaniv K.
Mineral Formation in the Larval Zebrafish Tail Bone Occurs via an Acidic Disordered Calcium Phosphate Phase
Journal of the American Chemical Society
Akiva A., Kerschnitzki M., Pinkas I., Wagermaier W., Yaniv K., Fratzl P., Addadi L. & Weiner S.
A new role of hindbrain boundaries as pools of neural stem/progenitor cells regulated by Sox2
BMC Biol
Peretz Y, Eren N, Kohl A, Hen G, Yaniv K, Weisinger K, Cinnamon Y, Sela-Donenfeld D.
2015
Title
Journal
Authors
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Venous-derived angioblasts generate organ-specific vessels during zebrafish embryonic development.
Development
Yaniv K.
Lymphatic vessels arise from specialized angioblasts within a venous niche
Nature
Nicenboim J., Malkinson G., Lupo T., Asaf L., Sela Y., Mayseless O., Gibbs-Bar L., Senderovich N., Hashimshony T., Shin M. S., Jerafi-Vider A., Avraham-Davidi I., Krupalnik V., Hofi R., Almog G., Astin J. W., Golani O., Ben-Dor S., Crosier P. S., Herzog W., Lawson N. D., Hanna J. H., Yanai I. & Yaniv K.
On the pathway of mineral deposition in larval zebrafish caudal fin bone
Bone
Akiva A., Malkinson G., Masic A., Kerschnitzki M., Bennet M., Fratzl P., Addadi L., Weiner S. & Yaniv K.
Zebrafish as a model for apolipoprotein biology: comprehensive expression analysis and a role for ApoA-IV in regulating food intake
Disease Models & Mechanisms
Otis J. P., Zeituni E. M., Thierer J. H., Anderson J. L., Brown A. C., Boehm E. D., Cerchione D. M., Ceasrine A. M., Avraham-Davidi I., Tempelhof H., Yaniv K. & Farber S. A.
Development and origins of Zebrafish ocular vasculature
BMC Developmental Biology
Kaufman R., Weiss O., Sebbagh M., Ravid R., Gibbs-Bar L., Yaniv K. & Inbal A.
2014
Title
Journal
Authors
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Simultaneous Raman Microspectroscopy and Fluorescence Imaging of Bone Mineralization in Living Zebrafish Larvae
Biophysical Journal
Bennet M., Akiva A., Faivre D., Malkinson G., Yaniv K., Abdelilah-Seyfried S., Fratzl P. & Masic A.
2013
Title
Journal
Authors
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Lipid signaling in the endothelium
Experimental Cell Research
Avraham-Davidi I., Grunspan M. & Yaniv K.
Zebrafish as a Model for Monocarboxyl Transporter 8-Deficiency
Journal of Biological Chemistry
Vatine G. D., Zada D., Lerer-Goldshtein T., Tovin A., Malkinson G., Yaniv K. & Appelbaum L.
2012
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Journal
Authors
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S1P(1) inhibits sprouting angiogenesis during vascular development
Development
Ben Shoham S. A., Malkinson G., Krief S., Shwartz Y., Ely Y., Ferrara N., Yaniv K. & Zelzer E.
ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1
Nature Medicine
Yaniv K., Avraham-Davidi I., Ely Y., Pham V. N., Castranova D., Grunspan M., Malkinson G., Gibbs-Bar L., Mayseless O., Allmog G., Lo B., Warren C. M., Chen T. T., Ungos J., Kidd K., Shaw K., Rogachev I., Wan W., Murphy P. M. & Farber S. A.
2011
Title
Journal
Authors
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Motoneurons are essential for vascular pathfinding
Development
Lim A. H., Suli A., Yaniv K., Weinstein B., Li D. Y. & Chien C.
2009
Title
Journal
Authors
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Zebrafish as a new animal model to study lymphangiogenesis
Anatomical Science International
Isogai S., Hitomi J., Yaniv K. & Weinstein B. M.
Endothelial cells promote migration and proliferation of enteric neural crest cells via beta 1 integrin signaling
Developmental Biology
Nagy N., Mwizerwa O., Yaniv K., Carmel L., Pieretti-Vanmarcke R., Weinstein B. M. & Goldstein A. M.
2007
Title
Journal
Authors
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Live imaging of lymphatic development in the zebralish embryo
FASEB Journal
Yaniv K., Isogai S., Castranova D. & Weinstein B. M.
Imaging the developing lymphatic system using the zebrafish.
Novartis Foundation Symposium
Yaniv K., Isogai S., Castranova D., Dye L., Hitomi J. & Weinstein B. M.
2006
Title
Journal
Authors
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Live imaging of lymphatic development in the zebrafish
Nature Medicine
Yaniv K., Isogai S., Castranova D., Dye L., Hitomi J. & Weinstein B.
We are always seeking enthusiastic PhD students and postdoctoral fellows.
Excellent candidates are welcome to apply!
Contact Us
Dr. Karina Yaniv, Principal Investigator
Faculty Of Biology
Department of Biological Regulation
Max and Lillian Candiotty Building, Room 210
Weizmann Institute of Science
Rehovot 76100, ISRAEL
