Karina Yaniv

How do lymphatic vessels form?

Early lymphatic development

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.

zebrafish, heart, liver, pancreatic and intestinal vasculature

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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.

Karina Yaniv
Karina Yaniv

Research

Early lymphatic development

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.

zebrafish, heart, liver, pancreatic and intestinal vasculature

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

2016
Title Journal Authors Download PDF
Mineral Formation in the Larval Zebrafish Tail Bone Occurs via an Acidic Disordered Calcium Phosphate Phase Journal of the American Chemical Society Akiva, Anat; Kerschnitzki, Michael; Pinkas, Iddo; Wagermaier, Wolfgang; Yaniv, Karina; Fratzl, Peter; Addadi, Lia; Weiner, Steve;
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; Sela-Donenfeld, D
Development of the lymphatic system: new questions and paradigms. Development Semo J, Nicenboim J, Yaniv K.
Autotaxin-Lysophosphatidic Acid Axis Acts Downstream of Apoprotein B Lipoproteins in Endothelial Cells Arterioscler Thromb Vasc Biol Gibbs-Bar L, Tempelhof H, Ben-Hamo R, Ely Y, Brandis A, Hofi R, Almog G, Braun T, Feldmesser E, Efroni S, Yaniv K.
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.
The mid-developmental transition and the evolution of animal body plans NATURE Levin, M; Anavy, L; Cole, AG; Winter, E; Mostov, N; Khair, S; Senderovich, N; Kovalev, E; Silver, DH; Feder, M; Fernandez-Valverde, SL; Nakanishi, N; Simmons, D; Simakov, O; Larsson, T; Liu, SY; Jerafi-Vider, A; Yaniv, K; Ryan, JF; Martindale, MQ; Rink, JC; Arendt, D; Degnan, SM; Degnan, BM; Hashimshony, T; Yanai, I
2015
Title Journal Authors Download PDF
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; Jerafi-Vider, A; Avraham-Davidi, I; Krupalnik, V; Hofi, R; Almog, G; Astin, JW; Golani, O; Ben-Dor, S; Crosier, PS; Herzog, W; Lawson, ND; Hanna, JH; Yanai, I; 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, JP; Zeituni, EM; Thierer, JH; Anderson, JL; Brown, AC; Boehm, ED; Cerchione, DM; Ceasrine, AM; Avraham-Davidi, I; Tempelhof, H; Yaniv, K; Farber, SA
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
Venous-derived angioblasts generate organ-specific vessels during zebrafish embryonic development Development Hen, G; Nicenboim, J; Mayseless, O; Asaf, L; Shin, M; Busolin, G; Hofi, R; Almog, G; Tiso, N; Lawson, ND; 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
2014
Title Journal Authors Download PDF
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 Download PDF
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, GD; Zada, D; Lerer-Goldshtein, T; Tovin, A; Malkinson, G; Yaniv, K; Appelbaum, L
2012
Title Journal Authors Download PDF
S1P(1) inhibits sprouting angiogenesis during vascular development Development Ben Shoham, 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 Avraham-Davidi, I; Ely, Y; Pham, VN; Castranova, D; Grunspan, M; Malkinson, G; Gibbs-Bar, L; Mayseless, O; Allmog, G; Lo, B; Warren, CM; Chen, TT; Ungos, J; Kidd, K; Shaw, K; Rogachev, I; Wan, WZ; Murphy, PM; Farber, SA; Carmel, L; Shelness, GS; Iruela-Arispe, ML; Weinstein, BM; Yaniv, K
2011
Title Journal Authors Download PDF
Motoneurons are essential for vascular pathfinding Development Lim, AH; Suli, A; Yaniv, K; Weinstein, B; Li, DY; Chien, CB
2009
Title Journal Authors Download PDF
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.
Zebrafish as a new animal model to study lymphangiogenesis ANATOMICAL SCIENCE INTERNATIONAL Isogai, S; Hitomi, J; Yaniv, K; Weinstein, B M.
2007
Title Journal Authors Download PDF
Imaging the developing lymphatic system using the zebrafish. Novartis Foundation symposium Yaniv, K; Isogai, S; Castranova, D; Dye, L; Hitomi, J; Weinstein, B M
Live imaging of lymphatic development in the zebralish embryo FASEB JOURNAL Yaniv, K; Isogai, S; Castranova, D; Weinstein, B M.
2006
Title Journal Authors Download PDF
Live imaging of lymphatic development in the zebrafish NATURE MEDICINE Yaniv, K; Isogai, S; Castranova, D; Dye, L; Hitomi, J; Weinstein, BM

Group

Moshe Grunspan

Years: 2011-2016
Degree studied in the lab: Ph.D. student

Dr. Yogev Sela

Years: 2011-2016
Degree studied in the lab: Postdoctoral Fellow

Liron Gibbs Bar

Years: 2010-2015
Degree studied in the lab: Ph.D. student

Dr. Inbal Avraham-Davidi

Years: 2010-2015
Degree studied in the lab: Postdoctoral Fellow

Tal Lupo

Years: 2012-2015
Degree studied in the lab: M.Sc Student

Oded Mayseless

Years: 2011-2014
Degree studied in the lab: M.Sc Student

Dr. Guy Malkinson

Years: 2010-2014
Degree studied in the lab: Postdoctoral Fellow

Neta Strasser

Years: 2011-2013
Degree studied in the lab: M.Sc Student

 

Galleries

Press releases

Dr. Karina Yaniv to be honored with LE&RN’s 2016 Wendy Chaite Leadership Award
Kathy Bates presents 2016 Research Awards
TEDxWhiteCity - Shaping Life from the Shapeless: The Awesome Power of the Embryo
Dr. Karina Yaniv

haaretz - ד"ר קרינה יניב, מומחית להתפתחות עוברים: כולסטרול עשוי לעצור גידולים סרטניים
Ministry of Science-  נשים פורצות דרך במדע

lymphatic education & research network
GEN - Lymphatic Vessels Traced to Overlooked Embryonic Source
ISRAEL21c -  World’s first – Israeli scientists grow lymphatic cells in the lab
OraTv - Kathy Bates: My Battle With Lymphedema
aurora-israel - Resolviendo un acertijo linfático
ynet - תאים ורגישים: כלי הדם קשובים לשומן

Join us

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
 

karina.yaniv@weizmann.ac.il

Phone: +972-(0)8-9342224

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