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| Name |
| Santos, Marta |
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| Nationality |
| Portuguese |
| E-Mail |
| martadossantos@gmail.com |
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| 1st Degree |
| Biochemistry |
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| About the PhD |
| Field of Research |
| Lung Development |
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| Thesis Title |
| Mechanisms of Lung Development in Normal and Hypoplastic Lungs |
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| Abstract |
| Congenital defects cause high infant mortality and Congenital Diaphragmatic Hernia (CDH) remains the most life-threatening pathology with and incidence of 1 in 2500 newborns. In CDH, a disturbance during diaphragm development... |
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| Congenital defects cause high infant mortality and Congenital Diaphragmatic Hernia (CDH) remains the most life-threatening pathology with and incidence of 1 in 2500 newborns. In CDH, a disturbance during diaphragm development allows intraabdominal viscera to invade the fetal thoracic cavity during early stages of lung development. CDH infants possess respiratory distress primarily due to a lower number of airway and vascular generations, enhanced muscularity of peripheral arteries and overall delayed lung maturation. Pulmonary hypoplasia and hypertension related to CDH are the major causes for the common failure of the available treatment modalities. The fundaments of this dissertation consisted in the disentanglement of several molecular mechanisms involved in normal and in abnormal hypoplastic lung development, aiming to elucidate some aspect of CDH pathophysiology and contribute to novel clinically pertinent perspectives concerning lung hypoplasia treatment. Normal lung development involves two distinctively regulated complex processes consisting of different cellular phenomena, early branching morphogenesis and late maturation and differentiation processes, whereas, CDH abnormal lung development seems to involve distinct early and late gestational determinants. The first are related with disruption of branching morphogenesis, whereas the latter are primarily related to mechanical compression mediated by visceral thoracic herniation affecting essentially lung maturation and differentiation. The present dissertation focused on branching and differentiation processes during normal and hypoplastic lung development. After the demonstration that retinoids were clearly involved in regulation of early determinants, this work raised the relevance of secreted peptides, such as, neuroendocrine products, during normal and hypoplastic development. Moreover, a pioneer approach for the study of early determinants of CDH pathophysiology revealed unexpected roles for myosin light chains as important regulators of normal and abnormal pulmonary branching. Finally, our studies support a novel hypothesis where pulmonary neuroendocrine cells are proposed as sensors of fetal lung growth. |
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| Supervisor(s) |
| Prof. Dr. Jorge Correia-Pinto, Prof. Dra. Isabel Palmeirim |
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| Co-Supervisor(s) |
| Prof. Dr. Dick Tibboel, Prof. Dr. Robbert Rottier |
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| University |
| Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga; Erasmus Medical Center, Rotterdam, The Netherlands. |
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| Laboratory |
| Development and Neoplasia Group |
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| City |
| Braga |
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| Country |
| Portugal |
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| Date of Thesis Defence |
| 2006-12-12 |
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| After the PhD (Current Situation) |
| Position |
| Intelectual Property Consultant |
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| Institution |
| Clarke Modet & Co Portugal |
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| City |
| Porto |
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| Country |
| Portugal |
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| Relevant Publications |
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| Santos M, Bastos P, Gonzaga S, Roriz JM, Baptista MJ, Nogueira-Silva C, Melo-Rocha G, Henriques-Coelho T, Roncon-Albuquerque R, Leite-Moreira A, de Krijger R, Tibboel D, Rottier R, Correia-Pinto J. }3Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen induced congenital diaphragmatic hernia}4 Ped Res 2006 59: 531-537. |
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| Nogueira-Silva C, Santos M, Baptista MJ, Moura RS, Correia-Pinto J. }3IL-6 is constitutively expressed during lung morphogenesis and enhances fetal lung explant branching}4 Ped Res 2006 60: 530-536. |
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| Santos M, Nogueira-Silva C, Baptista MJ, Soares-Fernandes J, Moura RS, Correia-Pinto J. }3Pulmonary epithelial cell differentiation in the nitrofen-induced Congenital Diaphragmatic Hernia}4 J Pediatr Surg 2007 42:1231-1237. |
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| Santos M, Moura RS, Nogueira-Silva C, Ohlmeier S, Correia-Pinto J. }3Embryonic essential myosin light chain regulates fetal lung development in rats}4 Am J Respir Cell Mol Biol 2007 37: 330-338. |
| Publications |
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| Castro H, Sousa C, Santos M, Cordeiro-da-Silva A, Flohé L, Tomás AM. }3Complementary antioxidant defence by cytoplasmic and mitochondrial peroxiredoxins in Leishmania infantum}4 Free Radic Biol Med 2002 33: 1552-1562. |
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| Castro H, Sousa C, Novais M, Santos M, Budde H, Cordeiro-da-Silva A, Flohe L, Tomas AM. }3Two linked genes of Leishmania infantum encode tryparedoxins localised to cytosol and mitochondrion}4 Mol Biochem Parasitol 2004 136: 137-147. |
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| Baptista MJ, Recamán M, Melo-Rocha G, Nogueira-Silva C, Roriz JM, Fernandes JS, Gonzaga S, Santos M, Leite-Moreira AF, Areias JC, Correia-Pinto J. }3Myocardium expression of Connexin 43, SERCA2a and myosin heavy chains isoforms are preserved in nitrofen-induced CDH rat model}4 J Pediatr Surg 2006 41:1532-1538. |
| Last Update |
| 2014-04-10 09:12:10 |
| The responsibility for this page contents is entirely of the student/alumnus. |
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Program financially supported by
the National Foundation for
Science and Technology
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