Team Leader
Team Leader
TEAM LEADERS : Eric Camerer & Anne Eichmann
Mail : eric.camerer@inserm.fr / anne.eichmann@inserm.fr
PHONE :+33 1 53 98 79 54 (Eichmann)/
+33 1 53 98 80 48 (Camerer)
LOCALISATION : Labs 360&361, 3rd floor
DOCTORAL SCHOOL : ED 562 – BIO SCIENCE PARIS CITE – Université PARIS CITE
Research in our team concerns vascular system development and contribution to human pathologies. Endothelial cells (ECs) that constitute the vascular system proliferate and differentiate at the same rate as the organism grows, to ensure oxygen and nutriment supply of tissues and cells. In adults, vascular development becomes quiescent and EC proliferation occurs only in certain physiological situations (wound healing, physical exercise, pregnancy) and pathologies, including diabetes, ageing-associated macular degeneration, tissue ischemia (heart, brain, legs) and malignant tumors.
The long-term goal of the laboratory is to understand the cellular and molecular mechanisms controlling vascular patterning and contributing to vascular homeostasis in the mature organism. We aim to identify key molecular events underlying angiogenesis, lymphangiogenesis and arteriogenesis and to establish the principles governing development of the vertebrate vascular system. Vessel networks are vulnerable to diseases, and abnormal vascular development in cardiovascular disease, cancer and diabetes is the major cause of morbidity and mortality in the developed world. We expect that understanding mechanisms controlling developmental vessel patterning will lead to novel strategies to prevent these diseases.
1. Guidance of vascular patterning and vascular malformations
(Park et al. Circulation 2021; Genet G. et al. Nat. Comm. 2019; Ola R. et al. Circulation 2018; Ola R. et al. Nat. Comm 2016; Aspalter IM et al. Nat. Comm 2015; Larivée B. et al. Dev. Cell 2012; Del Toro R. et al. Blood 2010)
We have shown that in blood vessels, specialized endothelial cells called tip cells located at the extremities of growing capillary sprouts mediate guided vascular patterning. Tip cells exhibit characteristic features, including extension of filopodia that explore the tip cell environment, lack of a lumen and a slow proliferation rate. Following behind tip cells, other endothelial cells termed stalk cells form the capillary lumen and proliferate. Tip cell selection is induced by VEGF signaling through VEGFR2 and is suppressed in stalk cells by Delta- Notch and BMP9-Alk1 signaling. These discoveries have profoundly affected scientific thinking about vascular patterning and reveals novel signaling pathway that could be targeted in patients with vascular malformations such as hereditary hemorrhagic telangiectasia.
2. Guidance receptor signaling in physiological and pathological angiogenesis
(Geraldo L. et al. JCI 2021; Zhang F. et al. Nat. Comm 2016; Rama N. et al. Nat. Medicine 2015; Koch AW. et al. Dev. Cell 2011; Lu X. et al. Nature 2004)
We have shown that capillary sprouting shows morphological similarities to axon guidance. Like endothelial tip cells, axonal growth cones extend filopodia that sense and respond to extracellular guidance cues. My lab has identified several key molecules regulating capillary guidance that also function in axonal guidance, including UNC5B, a receptor for Netrin1 and Robo4 and Slit2 signaling through Robo1 and 2. Molecules regulating capillary patterning and guidance in development also operate during pathological angiogenesis and therefore represent targets for promoting or inhibiting conditions associated with aberrant vessel growth.
3. Lymphatic drainage of fluids, macromolecules and immune cells
(Jacob L. et al. J. Exp. Med 2022; Jacob et al. Nat. Comm 2019; Zhang F et al. Science 2018; Bouvrée K. et al. Circulation Research 2012; Xu Y. et al. Journal of Cell Biology 2010).
The lymphatic vasculature regulates fluid homeostasis, absorption of dietary lipids and immune system function. The absence of lymphatic vessels is lethal, and impaired lymphatic vessel development causes fluid and protein accumulation in the interstitium, resulting in lymphedema and a persistent inflammatory response. Lymphedema and chronic inflammation are aggravating factors in cardiovascular disease, and are progressive and lifelong conditions affecting millions of people for which curative treatments are not available. We have identified essential signaling molecules responsible for lymphatic fate specification, sprouting and maturation, opening novel opportunities to target these processes in therapeutic settings.
4. Regulation of Blood-CNS Barrier integrity in health and disease
(Furtado J. et al. PNAS 2024; Boyé K. et al. Nat. Comm. 2022; Del Gaudio et al., Cardiovascular Res, 2024)
Blood vessels in the central nervous system (CNS) form specialized blood-CNS barriers including the blood-brain barrier (BBB) and blood-retina barrier (BRB) that prevent entry of toxins and tightly control the movement of ions, molecules, and cells between the blood and the CNS, thereby ensuring neuronal function and protection. However, the impermeability of the BBB and BRB impedes drug and treatment delivery in various pathologies and the development of tailored therapeutic strategies designed to increase CNS barrier permeability “on-demand” is a critical yet unmet clinical need.
We have identified essential signaling molecules essential for BBB and BRB development and maintenance, opening avenues to increase drug delivery during various CNS diseases.
5. Sphingosine 1-phosphate signaling in vascular development and homeostasis
(Del Gaudio et al., Cardiovascular Res, 2024; Nitzsche et al. Circ Res 2021; Niazi et al Blood Adv 2019; Gazit et al ,Circ Res 2016)
Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator that is produced by erythrocytes and platelets and circulates in plasma bound to high density lipoproteins (HDL) and albumin. S1P plays essential roles in the development and homeostasis of vascular and immune systems through actions on a small family of cognate G protein-coupled S1P receptors (S1PR1-5). We have addressed essential functions and mechanisms of engagement of S1PRs in the vascular system and explored the potential benefits and risks of targeting S1P receptors in cardiovascular disease.
6. Protease signaling in vascular biology and host defense
(Le Gall et al, Blood 2016; Friis S et al, BMC Biol 2017; Kawaguchi M et al, 2020; Szabo et al, PLoS Gent, 2014, Frateschi et al, Nat Commun 2011)
Serine proteases can modulate cellular behavior by proteolytic activation of protease-activated G protein-coupled receptors that carry their own tethered ligands (PARs). PAR signaling plays important roles in vascular development and in hemostasis by coordinating endothelial and platelet responses to activation of the coagulation cascade. We have contributed to the discovery of novel PAR agonists, cross-talk between coagulation proteases and membrane-anchored serine proteases, and roles for protease signaling in epithelial inflammation and cancer. Our current work is focused on roles of protease signaling in placental development and in vascular maturation during later stages of fetal development.
Team Leader
Team Leader
CRCN
CRCN
Engineer
Engineer
Engineer
Engineer
Postdoctoral Fellow
Postdoctoral Fellow
Postdoctoral Fellow
PhD Student
PhD Student
Eric Camerer
2010 : Marie Curie Reintegration Fellow
2009 : Inserm Avenir Young Investigator Award
2009 : FRM Young Investigator Award
2008 : CVRI Fellow, UCSF
2002 : Julius H. Comroe Fellow, UCSF
2000 : AHA Postdoctoral Fellow
1997 : Norwegian Research Council Fellow
1997 : HM King Harald’s Gold Medal , University of Oslo
Anne Eichmann
2025: Earl Bandit Award, NAVBO
2019 : Judah Folkman Award, NAVBO
2018: EMBO plenary lecture, IVBM
2013: Elected EMBO member
2009: Liliane Bettencourt prize for Life Sciences
2009: Chevalier de l’ordre national du mérite
2008: Inserm Research Award
2006: Jean Bernard award from the Medical Research Foundation FRM
2006: Young investigator award, Simone and Cino Del Duca Foundation
2005: renewal of INSERM Avenir award for two years based on excellent performance
2002: Young investigator award, Schlumberger Foundation
2002: INSERM young investigator Avenir award
1999: Young investigator award, Ministère de l’Education et de la Recherche (ACI)
1996: EMBO short-term fellowship award
Kevin Boyé
2022: Best oral presentation award “Early Career Researchers Congress”
2021: Young investigator award “The Leducq foundation ATTRACT network”
2020: Best postdoctoral poster award “NAVBO vascular biology 2020 meeting”
2019: Best postdoctoral poster award “Yale Vascular Biology and Therapeutics meeting”
2019: Travel award for NAVBO Vascular Biology international meeting
2018: American Heart Association postdoctoral fellow
2018: Philippe Foundation award
2017: Best postdoctoral poster award “Yale Vascular Biology and Therapeutics meeting”
2015: Travel award “Research and Practical Training in Taiwan”, Taiwan
2014: Travel award: “Partenariat Hubert Curien”, PHC ORCHID, Taiwan
Gaétan Braud
2025: Miller Junior Scientists Award – Cerebral Vascular Biology international meeting
Ongoing:
ANR “SphingoDrain” (2025 – 2029; Camerer PI) – SphingoDrain: New mechanisms and targets for brain drainage
INCa PLBIO 2025 (2025 – 2029; Boye PI) – Targeting brain tumors beyond the Blood-Brain Barrier
ANR “Beyond BBB” (2025 – 2029; Boye PI) – Drug delivery beyond the Blood-Brain Barrier
FRM Young Investigator (2023-26; Boye PI) – Signaling pathways that control the blood-brain barrier
ERC Advanced Grant « Breaking Barriers » (2019-2025; Eichmann) – Targeting endothelial barriers to combat disease
ANR « EtherIsch » (2021-2025; Camerer PI) – Endothelial therapy for ischemic stroke
ANR « iCare » (2021-2025; Mallat PI; Camerer Partner) – Early intermittent hypercholesetrolaemia, arterial macrophages & atherosclerosis
Interplay between Netrin-1 and Norrin controls arteriovenous zonation of blood-retina barrier integrity
Jessica Furtado, Luiz Henrique Geraldo, Felipe Saceanu Leser, Bartlomiej Bartkowiak, Mathilde Poulet, Hyojin Park, Mark Robinson, Laurence Pibouin-Fragner, Anne Eichmann #, Kevin Boyé#
Proc Natl Acad Sci U S A. 2024;121(52):e2408674121
Monoclonal antibodies that block Roundabout 1 and 2 signaling target pathological ocular neovascularization through myeloid cells
Luiz Henrique Geraldo, Yunling Xu, Gaspard Mouthon, Jessica Furtado, Felipe Saceanu Leser, Levi L Blazer, Jarrett J Adams, Sophia Zhang, Lana Zheng, Eric Song, Mark E Robinson, Jean-Leon Thomas, Sachdev S Sidhu, Anne Eichmann
Sci Transl Med. 2024 Nov 20;16(774)
Zonation and ligand and dose dependence of sphingosine 1-phosphate receptor-1 signalling in blood and lymphatic vasculature
Ilaria Del Gaudio#, Anja Nitzsche#, Kevin Boyé, Philippe Bonnin, Mathilde Poulet, Toan Q Nguyen, Ludovic Couty, Hoa T T Ha, Dat T Nguyen, Amaury Cazenave-Gassiot, Khaoula Ben Alaya, Patrice Thérond, Jerold Chun, Markus R Wenk, Richard L Proia, Daniel Henrion, Long N Nguyen, Anne Eichmann, Eric Camerer
Cardiovasc Res 2024 120 (14), 1794-1810
Vascular development, remodeling and maturation
Jessica Furtado, Anne Eichmann
Curr Top Dev Biol. 2024;159:344-370.
Chylomicrons regulate lacteal permeability and intestinal lipid absorption
Georgia Zarkada, Xun Chen, Xuetong Zhou, Martin Lange, Lei Zeng, Wenyu Lv, Xuan Zhang, Yunhua Li, Weibin Zhou, Keli Liu, Dongying Chen, Nicolas Ricard, James Liao, Young-Bum Kim, Rui Benedito, Lena Claesson-Welsh, Kari Alitalo, Michael Simons, Rong Ju, Xuri Li, Anne Eichmann, Feng Zhang
Circulation Research 2023 133 (4), 333-349
CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma
Luiz Henrique Geraldo, Celina Garcia, Yunling Xu, Felipe Saceanu Leser, Izabella Grimaldi, Eduardo Sabino de Camargo Magalhães, Joost Dejaegher, Lien Solie, Cláudia Maria Pereira, Ana Helena Correia, Steven De Vleeschouwer, Bertrand Tavitian, Nathalie Henriques Silva Canedo, Thomas Mathivet, Jean-Leon Thomas, Anne Eichmann, Flavia Regina Souza Lima
Cellular and Molecular Life Sciences 2023 80 (7), 179
Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice
Sungwoon Lee, Hubertus Schleer, Hyojin Park, Erika Jang, Michael Boyer, Bo Tao, Ana Gamez-Mendez, Abhishek Singh, Ewa Folta-Stogniew, Xinbo Zhang, Lingfeng Qin, Xue Xiao, Lin Xu, Junhui Zhang, Xiaoyue Hu, Evanthia Pashos, George Tellides, Philip W Shaul, Warren L Lee, Carlos Fernandez-Hernando, Anne Eichmann, William C Sessa
Nature Cardiovascular Research 2023, 1-11
Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock
Thanh Nha Uyen Le, Toan Q Nguyen, Pazhanichamy Kalailingam, Yen Thi Kim Nguyen, Viresh Krishnan Sukumar, Clarissa Kai Hui Tan, Farhana Tukijan , Ludovic Couty, Zafrul Hasan, Ilaria Del Gaudio, Markus R Wenk, Amaury Cazenave-Gassiot, Eric Camerer, Long N Nguyen
Cell Rep. 2022 Aug 16;40(7):111208.
Environmental and intrinsic modulations of venous differentiation
Laurence Pibouin-Fragner, Anne Eichmann, Luc Pardanaud
Cellular and Molecular Life Sciences 2022 79 (9), 491
Conserved meningeal lymphatic drainage circuits in mice and humans
Laurent Jacob, Jose de Brito Neto, Stephanie Lenck, Celine Corcy, Farhat Benbelkacem, Luiz Henrique Geraldo, Yunling Xu, Jean-Mickael Thomas, Marie-Renee El Kamouh, Myriam Spajer, Marie-Claude Potier, Stephane Haik, Michel Kalamarides, Bruno Stankoff, Stephane Lehericy, Anne Eichmann, Jean-Leon Thomas
Journal of Experimental Medicine 2022 219 (8), e20220035
Distinct GEFs Couple S1PR1 to Rac for Endothelial Barrier Enhancement and Lymphocyte Trafficking
Ilaria Del Gaudio, Eric Camerer
Arterioscler Thromb Vasc Biol. 2022 Jul;42(7):903-905
Endothelial Unc5B controls blood-brain barrier integrity
Kevin Boyé, Luiz Henrique Geraldo, Jessica Furtado, Laurence Pibouin-Fragner, Mathilde Poulet, Doyeun Kim, Bryce Nelson, Yunling Xu, Laurent Jacob, Nawal Maissa, Dritan Agalliu, Lena Claesson-Welsh, Susan L Ackerman, Anne Eichmann
Nature Communications 2022 13 (1), 1169
Defective flow-migration coupling causes arteriovenous malformations in hereditary hemorrhagic telangiectasia
Hyojin Park, Jessica Furtado, Mathilde Poulet, Minhwan Chung, Sanguk Yun, Sungwoon Lee, William C Sessa, Claudio A Franco, Martin A Schwartz, Anne Eichmann
Circulation 2021 144 (10), 805-822
Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development
Jinyu Li, Luiz Henrique Geraldo, Alexandre Dubrac, Georgia Zarkada, Anne Eichmann
Journal of the American Society of Nephrology 2021: JASN 32 (9), 2255
SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia
Luiz H Geraldo, Yunling Xu, Laurent Jacob, Laurence Pibouin-Fragner, Rohit Rao, Nawal Maissa, Maïté Verreault, Nolwenn Lemaire, Camille Knosp, Corinne Lesaffre, Thomas Daubon, Joost Dejaegher, Lien Solie, Justine Rudewicz, Thomas Viel, Bertrand Tavitian, Steven De Vleeschouwer, Marc Sanson, Andreas Bikfalvi, Ahmed Idbaih, Q Richard Lu, Flavia RS Lima, Jean-Leon Thomas, Anne Eichmann, Thomas Mathivet
The Journal of clinical investigation 2021 131 (16)
Specialized endothelial tip cells guide neuroretina vascularization and blood-retina-barrier formation
Georgia Zarkada, Joel P Howard, Xue Xiao, Hyojin Park, Mathilde Bizou, Severine Leclerc, Steffen E Künzel, Blanche Boisseau, Jinyu Li, Gael Cagnone, Jean Sebastien Joyal, Gregor Andelfinger, Anne Eichmann, Alexandre Dubrac
Developmental cell 2021 56 (15), 2237-2251. e6
Stop the Divide and Build Coronary Arteries
G Zarkada, A Eichmann
Developmental Cell 2021 56 (3), 255-256
Endothelial S1P1 Signaling Counteracts Infarct Expansion in Ischemic Stroke
Anja Nitzsche#, Marine Poittevin#, Ammar Benarab#, Philippe Bonnin#, Giuseppe Faraco, Hiroki Uchida, Julie Favre, Lidia Garcia-Bonilla, Manuela C L Garcia, Pierre-Louis Léger, Patrice Thérond , Thomas Mathivet, Gwennhael Autret, Véronique Baudrie, Ludovic Couty, Mari Kono, Aline Chevallier, Hira Niazi, Pierre-Louis Tharaux, Jerold Chun, Susan R Schwab , Anne Eichmann, Bertrand Tavitian, Richard L Proia 11, Christiane Charriaut-Marlangue, Teresa Sanchez, Nathalie Kubis, Daniel Henrion, Costantino Iadecola, Timothy Hla, Eric Camerer
Circ Res. 2021 Feb 5;128(3):363-382
Platelets maintain vascular barrier function in the absence of injury or inflammation
Benoit Ho-Tin-Noé, Ophélie Le Chapelain, Eric Camerer
J Thromb Haemost 2021;19:1145-48
Lymphatic endothelial cell junctions: molecular regulation in physiology and diseases
Feng Zhang, Georgia Zarkada, Sanjun Yi, Anne Eichmann
Frontiers in Physiology 2020 11, 509
Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta
Eric Engelbrecht#, Michel V Levesque#, Liqun He, Michael Vanlandewijck, Anja Nitzsche, Hira Niazi, Andrew Kuo, Sasha A Singh, Masanori Aikawa, Kristina Holton, Richard L Proia, Mari Kono, William T Pu, Eric Camerer , Christer Betsholtz, Timothy Hla
Elife. 2020 Feb 24;9:e52690
Anatomy and function of the vertebral column lymphatic network in mice
Laurent Jacob, Ligia Simoes Braga Boisserand, Luiz Henrique Medeiros Geraldo, Jose de Brito Neto, Thomas Mathivet, Salli Antila, Besma Barka, Yunling Xu, Jean-Mickael Thomas, Juliette Pestel, Marie-Stéphane Aigrot, Eric Song, Harri Nurmi, Seyoung Lee, Kari Alitalo, Nicolas Renier, Anne Eichmann, Jean-Leon Thomas
Nature Communications 2019 10 (1), 4594
Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis
Gael Genet, Kevin Boyé, Thomas Mathivet, Roxana Ola, Feng Zhang, Alexandre Dubrac, Jinyu Li, Nafiisha Genet, Luiz Henrique Geraldo, Lorena Benedetti, Steffen Künzel, Laurence Pibouin-Fragner, Jean-Leon Thomas, Anne Eichmann
Nature Communications 2019 10 (1), 2350
Murine platelet production is suppressed by S1P release in the hematopoietic niche, not facilitated by blood S1P sensing
Hira Niazi, Nesrine Zoghdani, Ludovic Couty, Alexandre Leuci, Anja Nitzsche, Maria L Allende, Boubacar Mariko, Rameez Ishaq , Yetki Aslan, Pierre Hadrien Becker, Salomé L Gazit, Sonia Poirault-Chassac, Benoit Decouture, Veronique Baudrie, Erica De Candia, Mari Kono, Ammar Benarab, Pascale Gaussem, Pierre-Louis Tharaux, Jerold Chun, Sylvain Provot, Najet Debili, Patrice Therond, Richard L Proia, Christilla Bachelot-Loza, Eric Camerer
Blood Adv 2019;3:1702-1713
SMAD4 prevents flow induced arteriovenous malformations by inhibiting casein kinase 2
Roxana Ola, Sandrine H Künzel, Feng Zhang, Gael Genet, Raja Chakraborty, Laurence Pibouin-Fragner, Kathleen Martin, William Sessa, Alexandre Dubrac, Anne Eichmann
Circulation 2018 138 (21), 2379-2394
NCK-dependent pericyte migration promotes pathological neovascularization in ischemic retinopathy
Alexandre Dubrac, Steffen E Künzel, Sandrine H Künzel, Jinyu Li, Rachana Radhamani Chandran, Kathleen Martin, Daniel M Greif, Ralf H Adams, Anne Eichmann
Nature Communications 2018 9 (1), 3463
Lacteal junction zippering protects against diet-induced obesity
Feng Zhang, Georgia Zarkada, Jinah Han, Jinyu Li, Alexandre Dubrac, Roxana Ola, Gael Genet, Kevin Boyé, Pauline Michon, Steffen E Künzel, Joao Paulo Camporez, Abhishek K Singh, Guo-Hua Fong, Michael Simons, Patrick Tso, Carlos Fernández-Hernando, Gerald I Shulman, William C Sessa, Anne Eichmann
Science 2018 361 (6402), 599-603
Platelets and vascular integrity: how platelets prevent bleeding in inflammation.
Benoit Ho-Tin-Noé, Yacine Boulaftali, Eric Camerer
Blood. 2018;131:277-288.
