Group of Investigation in Tumor Angiogenesis (GIANT)

• Main focus of our laboratory is understanding of angiogenesis alterations in offspring born to preeclampsia, a pregnancy condition characterized by maternal hypertension and systemic endothelial dysfunction.
• Our scientific production has used human placenta as a model of angiogenesis and as a source of endothelial cells from micro and macrocirculation.
• We have been focused in the role of three main actors in the angiogenesis process: adenosine A_2A receptor (A_2A), nitric oxide (NO), and vascular endothelial growth factor (VEGF). These three actors constitute an autoregulatory loop, that is impair in preeclampsia. In vitro experiments have extended to animal models of preeclampsia-like syndrome.
• Currently, we have focused into vascular brain alterations in both offspring and mothers exposed to preeclampsia.

• Cell culture room full equipped; Microscopy (inverse, fluorescent); Equipment for cellular and molecular biology (PCR, Western blot, immunocytochemistry); Animal facilities (blood pressure, anesthesia machine, housing, ventilated rack); in vivo blood perfusion analysis (Speckle Laser Doppler).

• In our laboratory we seek to explain pathophysiological phenomena from molecular and cellular levels, as well as translational medicine using mice models and human tissue (placenta).  Therefore, available techniques are isolation and primary culture of different kind of endothelial cells (HUVEC, hPMEC, mPEC, mBEC) as well as cell line culture (HUVEC, hCMEC/D3, hDMEC). We combine information with mathematical models. Biological techniques include RT-PCR, qPCR,  DNA-cloning, Western  blot,  cell  fractionation, siRNA, electroporation, etc. In vivo analysis include mice model of preeclampsia (L-NAME injection); microsurgery; in vivo perfusion analysis.

• Fully open to collaborate in vascular placental physiology and pregnancy pathologies. Current focus of research: angiogenesis, brain vasculature, VEGF receptors.

• DIUBB 184309 4/R (Escudero C) 1/1/2018-1/1/2020.
  University of Bio Bio
  Role of placental growth factor in the cerebral perfusion of pups coming from hypertensive pregnancies.
  This grant aim to characterize the expression of placental growth factor (PlGF) in brain microcirculation of offspring born to hypertensive pregnancies.
• DIUBB GI 171709/VC (Escudero C) 6/1/2017- 6/1/2019
  University of Bio Bio
  Hybrid approach for investigating tumor angiogenesis. GIANT (Consolidation grant)
  This grant aims to combine mathematical and biological analysis in order to better understand tumor growth and tumor angiogenesis.
• REDI170287 (Guzman-Gutierrez E) 11/1/2017-11/1/2019
  Strengthening of the cooperation network for the study of vascular disorders associated with pregnancy disorders in Latin America (Co-Director)
  This grant is aimed to increase scientific interaction between Latin American faculties focused in the field of vascular biology and pregnancy complications. In this network are participating Faculties from Argentina, Brazil, Colombia, Mexico, Spain, Ecuador, USA, and Chile. And will extend to Cuba and Bolivia.
• REDI170373 (Torres-Vergara P) 11/1/2017-11/1/2019
  Multidisciplinary network for the analysis of the physiopathological mechanisms underlying the cerebral endothelial damage present in preeclampsia
  (Co-Director)
  This grant is aimed to increase scientific interaction between faculties focused in the field of brain vascular alterations in women and offspring exposed to preeclampsia. This network include faculties form the following universities; Manchester, Uppsala, Pittsburgh, Concepcion and Bio Bio (Chile).

Support completed in the last 3 years

• DIUBB 166709 3/R (Rodriguez A) 5/1/2016-5/1/2018
  Effect of A_2A adenosine receptor in the formation of tumor blood vessels.
  (Co-investigator)
  This grant aimed to investigate the role of the pro-angiogenic receptor, A_2A adenosine receptor in the field of tumor angiogenesis. For that we used A_2AKO mice. This mice model was also used for studying placental vessel alterations.
• FONDEQUIP EQM140104 (Escudero C) 10/2014-10-2017
  In vivo study of microcirculation in animal models and their clinical projections.
  Project aimed to get Laser Doppler machine for studying microcirculation during in vivo studies. This equipment is unique in Chile.
• FONDECYT Regular 1140586 (Escudero C) 3/15/2014-3/15/2018
  Role of angiogenesis mediated by the A_2A AR/VEGF signaling pathway in the generation of hypertension in offspring born from pre-eclamptic pregnancies
  This study generates a better understanding of A_2A/VEGF signaling in the angiogenesis process and how it may be impaired in offspring from preeclampsia.  Also, this grant allows us to include analysis of blood perfusion in children born to preeclampsia.
• PEAUCCH-03-2017 (Rodriguez A) 12/2016-12/2017
  University of Bio Bio, Extension center
  Organization of the 2^nd Meeting on Research and Innovation in Vascular Health, 4^th Meeting on Hypertension in Pregnancy
  Aimed to organize an international meeting in which investigators focused in vascular biology were concentrated in Chillan, Chile. Meeting joints more than 120 attendees, 80% of them were middle- carrier faculties. The spirit of this meeting is become a platform of multidisciplinary collaborative work.
• GI 152920/EF (Parra J) 4/2015-4/2017
  Group of investigation of nutrition applied to obesity
  (Co-investigator)
  This grant aims to joint researchers from different Schools and Faculties belong to University of Bio Bio addressed to investigate underling mechanisms of obesity and how implement viable strategies to reduce this highly prevalent disease.
• GI153109/EF (Escudero C) 4/2015-4/2017
  Hybrid approach for investigating tumor angiogenesis. GIANT (Beginning grant)
  This grant aims to combine mathematical and biological analysis in order to better understand tumor growth and tumor angiogenesis.

Our whole contribution (68 ISI and not ISI papers; 7 book chapters) has received more than 1000 citation. Current H index is 17. Please, find our complete list of published work at (https://www.researchgate.net/profile/Carlos_Escudero2).

 Selected key publications

• Giachini F, Galaviz-Hernandez C, Damiano AE, Viana M, Cadavid A, Asturizaga P, Teran E, Clapes S, Alcala M, Bueno J, Calderón-Domínguez M, Ramos MP, Lima VV, Sosa-Macias M, Martinez N, Roberts JM, and Escudero C on behalf of RIVA-TREM. Vascular dysfunction in mother and offspring during preeclampsia: Contributions from Latin American countries. Current Hypertension Reports. (2017) 19: 83. https://doi.org/10.1007/s11906-017-0781-7.
• Escudero C, Casanello P, Sobrevia L. Human equilibrative nucleoside transporters 1 and 2 may be differentially modulated by A2B adenosine receptors in placenta microvascular endothelial cells from pre-eclampsia. Placenta. 2008;29(9):816-25. Epub 2008/08/16. doi: 10.1016/j.placenta.2008.06.014. PubMed PMID: 18703227.
• Escudero C, Celis C, Saez T, San Martin S, Valenzuela FJ, Aguayo C, et al. Increased placental angiogenesis in late and early onset pre-eclampsia is associated with differential activation of vascular endothelial growth factor receptor 2. Placenta. 2014;35(3):207-15. Epub 2014/02/11. doi: 10.1016/j.placenta.2014.01.007. PubMed PMID: 24508097.
• Escudero C, Bertoglia P, Hernadez M, Celis C, Gonzalez M, Aguayo C, et al. Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset preeclampsia. Purinergic Signal. 2013;9(2):215-26. doi: 10.1007/s11302-012-9341-4. PubMed PMID: 23179048; PubMed Central PMCID: PMCPMC3646121.
• Acurio J, Herlitz K, Troncoso F, Aguayo C, Bertoglia P, Escudero C. Adenosine A2A receptor regulates expression of vascular endothelial growth factor in feto-placental endothelium from normal and late-onset pre-eclamptic pregnancies. Purinergic Signal. 2016. doi: 10.1007/s11302-016-9538-z. PubMed PMID: 27696086.