Contributions to the Yearbook of the Max Planck Society

2019

  • Regulation of Notch signaling dynamics by deubiquitinating enzymes

    2019 Potente, Michael
    The Notch signaling pathway is a highly conserved cell-cell communication mechanism that governs the development of and function of body tissues. We found that the enzyme USP10 is a novel regulator of this pathway, whose activity is particularly important for the growth of new blood vessels. Our studies revealed new insights into the molecular fundamentals of blood vessel development and could also have relevance for other physiological and pathological processes in which Notch signaling pathway plays a pivotal role.
  • A critical factor of patient survival and a potential treatment strategy for angiosarcoma

    2019 Riddell, Meghan; Hikita, Takao; Nakayama, Masanori

    Cell polarity is a fundamental feature that is required for proper tissue function. Loss of polarity causes tissue disorganization and excessive cell growth. In highly malignant tumors, the polarity protein aPKCλ is often over-expressed and mislocalized  However, the molecular mechanisms connecting cell polarization to cell proliferation so far remained elusive. We identified a critical factor for patient prognosis and propose a novel therapeutic strategy.

2018

  • Breath test enables early detection of lung cancer

    2018 Barreto, Guillermo
    Lung cancer is the leading cause of death from cancer globally. One reason for this is that early signs and symptoms are unspecific and most lung tumors are recognized at an advanced stage. The Max Planck scientists have developed a test to detect lung cancer in early stages. It is based on the detection of genes that are active in tumor cells, but not in healthy lung cells.
  • Regulation of Notch signaling dynamics by deubiquitinating enzymes

    2018 Potente, Michael
    The Notch signaling pathway is a highly conserved cell-cell communication mechanism that governs the development of and function of body tissues. We found that the enzyme USP10 is a novel regulator of this pathway, whose activity is particularly important for the growth of new blood vessels. Our studies revealed new insights into the molecular fundamentals of blood vessel development and could also have relevance for other physiological and pathological processes in which Notch signaling pathway plays a pivotal role.

2017

  • From lung development to lung regeneration

    2017 Ahlbrecht, Katrin; Morty, Rory E.; Samakovlis, Christos; Seeger, Werner

    Impairment of gas exchange due to malformation or disruption of the alveoli represents a key hallmark of structural lung diseases. There is no curative therapy available. The recovery of an intact lung structure represents a desirable option in the development of therapeutic concepts. The current knowledge about the formation of new alveoli during lung development and during compensatory lung growth of the adult lung serves as a basis for the identification of target cells and molecules which are capable to induce the formation of new alveoli in the diseased lung.

  • Breath test enables early detection of lung cancer

    2017 Barreto, Guillermo
    Lung cancer is the leading cause of death from cancer globally. One reason for this is that early signs and symptoms are unspecific and most lung tumors are recognized at an advanced stage. The Max Planck scientists have developed a test to detect lung cancer in early stages. It is based on the detection of genes that are active in tumor cells, but not in healthy lung cells.

2016

  • miRNAs control essential functions of the cardiovascular system

    2016 Böttger, Thomas
    The primary function of miRNAs is the posttranscriptional regulation of gene expression. The functional analysis of miRNA-mediated regulation allows fascinating insights into complex regulatory interactions. A group at the MPI of Heart and Lung Research investigates miRNA-dependent molecular mechanisms in contractile tissues of the cardiovascular system. The work reveals basic principles of miRNA regulation and answers fundamental questions related to development and physiology of the cardiovascular system.
  • From lung development to lung regeneration

    2016 Ahlbrecht, Katrin; Morty, Rory E.; Samakovlis, Christos; Seeger, Werner

    Impairment of gas exchange due to malformation or disruption of the alveoli represents a key hallmark of structural lung diseases. There is no curative therapy available. The recovery of an intact lung structure represents a desirable option in the development of therapeutic concepts. The current knowledge about the formation of new alveoli during lung development and during compensatory lung growth of the adult lung serves as a basis for the identification of target cells and molecules which are capable to induce the formation of new alveoli in the diseased lung.

2015

  • G-protein-mediated signaling cascades in the cardiovascular and immune system

    2015 Wettschureck, Nina
    Heterotrimeric G-proteins transduce signals from activated G-protein-coupled receptors to intracellular signaling cascades. Scientists at the MPI for Heart and Lung Research have a longstanding interest in the role of the families Gq/G11 and G12/G13, their upstream activators and downstream effectors, in cardiovascular and immunological functions. The long-term goal of their work is to identify new targets for the treatment of chronic cardiovascular and immune disease.
  • miRNAs control essential functions of the cardiovascular system

    2015 Böttger, Thomas
    The primary function of miRNAs is the posttranscriptional regulation of gene expression. The functional analysis of miRNA-mediated regulation allows fascinating insights into complex regulatory interactions. A group at the MPI of Heart and Lung Research investigates miRNA-dependent molecular mechanisms in contractile tissues of the cardiovascular system. The work reveals basic principles of miRNA regulation and answers fundamental questions related to development and physiology of the cardiovascular system.

2014

  • The ERBB2 receptor: a necessary proto oncogene

    2014 Reischauer, Sven

    During development cardiac morphogenesis relies on the concerted activity of several growth factor receptors including the proto oncogene ERBB2. In adults, its cardiotoxicity causes severe side effects in anti-ERBB2 cancer therapies. Therefore we developed a transgenic zebrafish line to elucidate the role of ErbB2 signaling in cardiomyocytes. Using this novel tool combined with state-of-the-art microscopy, we were able to identify ErbB2 as a mediator of remodeling of the contractile machinery, an unexpected mechanism with potentially important implications to human health.

  • G-protein-mediated signaling cascades in the cardiovascular and immune system

    2014 Wettschureck, Nina
    Heterotrimeric G-proteins transduce signals from activated G-protein-coupled receptors to intracellular signaling cascades. Scientists at the MPI for Heart and Lung Research have a longstanding interest in the role of the families Gq/G11 and G12/G13, their upstream activators and downstream effectors, in cardiovascular and immunological functions. The long-term goal of their work is to identify new targets for the treatment of chronic cardiovascular and immune disease.

2013

  • Quantitative mass spectrometric proteome analysis

    2013 Krüger, Marcus
    Living cells contain a variety of complex structures that control the homeostasis and communication. The systematic study of those structures on DNA, transcript and protein level has become one of the standard techniques in medical research. Recently, mass spectrometric techniques helped to explore the enormous complexity of the proteome. To achieve accurate protein quantification, the labeling of proteins with stable isotopes (also known as SILAC, stable isotope labeling of amino acids in cell culture) was recently established.
  • The ERBB2 receptor: a necessary proto oncogene

    2013 Reischauer, Sven

    During development cardiac morphogenesis relies on the concerted activity of several growth factor receptors including the proto oncogene ERBB2. In adults, its cardiotoxicity causes severe side effects in anti-ERBB2 cancer therapies. Therefore we developed a transgenic zebrafish line to elucidate the role of ErbB2 signaling in cardiomyocytes. Using this novel tool combined with state-of-the-art microscopy, we were able to identify ErbB2 as a mediator of remodeling of the contractile machinery, an unexpected mechanism with potentially important implications to human health.

2012

  • Heart and Lung – from Development to Therapy

    2012 Barreto, Guillermo; Dobreva, Gergana; Engel, Felix B.; Savai, Rajkumar
    Heart and lung diseases represent a major disease burden and socioeconomic problem. Ischemic heart disease is the leading single cause of mortality, congenital heart disease the most common type of birth defect and lung cancer the leading cause of cancer mortality worldwide. Current therapeutic efforts to treat those diseases are limited to the symptoms and rarely target the primary cause. Therefore it is important to develop better tools for early diagnosis and novel therapeutic strategies, e.g. through a better understanding of the regulatory mechanisms of heart and lung development.
  • Quantitative mass spectrometric proteome analysis

    2012 Krüger, Marcus
    Living cells contain a variety of complex structures that control the homeostasis and communication. The systematic study of those structures on DNA, transcript and protein level has become one of the standard techniques in medical research. Recently, mass spectrometric techniques helped to explore the enormous complexity of the proteome. To achieve accurate protein quantification, the labeling of proteins with stable isotopes (also known as SILAC, stable isotope labeling of amino acids in cell culture) was recently established.

2011

  • Lung oedema: Molecular mechanisms of development

    2011 Morty, Rory Edward; Seeger, Werner
    Impair fluid balance in the lung is a key characteristic of acute respiratory distress syndrome (ARDS), a life-threatening syndrome frequently encountered in an intensive care setting. The molecular processes underlying impaired fluid clearance are not understood. Recently, the peptide hormone transforming growth factor (TGF)-β has been implicated as a regulator of lung fluid balance, modulating the activity of both components of a two-component Na+ transport mechanism of the alveolar epithelium involving the epithelial sodium channel (ENaC) and the Na+/K+-ATPase, a sodium/potassium ion pump.
  • Heart and Lung – from Development to Therapy

    2011 Barreto, Guillermo; Dobreva, Gergana; Engel, Felix B.; Savai, Rajkumar
    Heart and lung diseases represent a major disease burden and socioeconomic problem. Ischemic heart disease is the leading single cause of mortality, congenital heart disease the most common type of birth defect and lung cancer the leading cause of cancer mortality worldwide. Current therapeutic efforts to treat those diseases are limited to the symptoms and rarely target the primary cause. Therefore it is important to develop better tools for early diagnosis and novel therapeutic strategies, e.g. through a better understanding of the regulatory mechanisms of heart and lung development.

2010

  • High blood pressure, shock, atherosclerosis – dysregulations of the blood vessel system

    2010 Offermanns, Stefan
    The wall of blood vessels consists of smooth muscle cells and of the endothelium, which lines the inner surface of the vessel. Various mediators, which in most cases act via G-protein-coupled receptors, regulate the contractile state as well as the permeability of the blood vessel wall. Defects in these regulatory processes can cause common diseases like hypertension, shock, or atherosclerosis. Recently, at the MPI for Heart and Lung Research new insights have been gained into the mechanisms underlying the regulation of vascular wall cells by various mediators as well as into the role of these processes in vascular diseases.
  • Lung oedema: Molecular mechanisms of development

    2010 Morty, Rory Edward; Seeger, Werner
    Impair fluid balance in the lung is a key characteristic of acute respiratory distress syndrome (ARDS), a life-threatening syndrome frequently encountered in an intensive care setting. The molecular processes underlying impaired fluid clearance are not understood. Recently, the peptide hormone transforming growth factor (TGF)-β has been implicated as a regulator of lung fluid balance, modulating the activity of both components of a two-component Na+ transport mechanism of the alveolar epithelium involving the epithelial sodium channel (ENaC) and the Na+/K+-ATPase, a sodium/potassium ion pump.

2009

  • Anti cancer drugs in pulmonary arterial hypertension

    2009 Schermuly, Ralph; Seeger, Werner
    Pulmonary vascular remodeling of lung arteries plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH). This leads to an accumulation of cells in the vessel wall and to a reduced vascular lumen. New therapeutic approaches try to reduce the benign proliferation and attempt to reverse the remodeling of the pulmonary arteries using anti-cancer drugs. In the focus of our interest are inhibitors of tyrosine-kinases, which showed promising effects in preclinical models of pulmonary hypertension and first clinical studies.
  • High blood pressure, shock, atherosclerosis – dysregulations of the blood vessel system

    2009 Offermanns, Stefan
    The wall of blood vessels consists of smooth muscle cells and of the endothelium, which lines the inner surface of the vessel. Various mediators, which in most cases act via G-protein-coupled receptors, regulate the contractile state as well as the permeability of the blood vessel wall. Defects in these regulatory processes can cause common diseases like hypertension, shock, or atherosclerosis. Recently, at the MPI for Heart and Lung Research new insights have been gained into the mechanisms underlying the regulation of vascular wall cells by various mediators as well as into the role of these processes in vascular diseases.

2008

  • Can Sirtuins combat aging?

    2008 Bober, Eva
    Sirtuins are highly conserved histon/protein deacetylases, which confer stress resistance and longevity. In mammals sirtuins are represented by a gene family that consists of seven genes, Sirt1 -Sirt7. In our project we investigate the molecular basis of sirtuin functions in mammals. The understanding of sirtuin function can contribute to developing new therapeutic strategies to combat and/or treat age-related diseases.
  • Anti cancer drugs in pulmonary arterial hypertension

    2008 Schermuly, Ralph; Seeger, Werner
    Pulmonary vascular remodeling of lung arteries plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH). This leads to an accumulation of cells in the vessel wall and to a reduced vascular lumen. New therapeutic approaches try to reduce the benign proliferation and attempt to reverse the remodeling of the pulmonary arteries using anti-cancer drugs. In the focus of our interest are inhibitors of tyrosine-kinases, which showed promising effects in preclinical models of pulmonary hypertension and first clinical studies.

2007

  • Plasticity of newt Cardiomyocytes

    2007 Borchardt, Thilo; Kostin, Sawa
    The mammalian heart is not able to regenerate lost cardiac tissue after substantial injuries, instead the heart is repaired by scar formation. Newts and Zebrafish however are able to fully regenerate their hearts without scarring. On of the current projects at the Max Planck Institute for Heart and Lung Research is to understand, how cardiac regeneration takes place in non-mammalian vertebrates. This could provide new approaches that stimulate regenerative pathways in the human heart.
  • Can Sirtuins combat aging?

    2007 Bober, Eva
    Sirtuins are highly conserved histon/protein deacetylases, which confer stress resistance and longevity. In mammals sirtuins are represented by a gene family that consists of seven genes, Sirt1 -Sirt7. In our project we investigate the molecular basis of sirtuin functions in mammals. The understanding of sirtuin function can contribute to developing new therapeutic strategies to combat and/or treat age-related diseases.

2006

  • The role of stem cells in regeneration and repair of organs

    2006 Belema Bedada, Fikru; Heil, Matthias
    The Max-Planck-Institute for Heart and Lung Research in Bad Nauheim focusses on research on the processes being responsible for regeneration and repair of organs such as the heart. Previous studies had shown that stem cells might play an important role. In one of their projects scientists therefore investigated the potential of adult and embryonal stem cells to differentiate into completely developed tissue cells such as skeletal muscle or heart muscle cells. Data show that the use of specific differention factors indeed induces cell programmes which lead to the expression of typical muscle-cell specific factors. However, stem cells could not completely be transfered into muscle cells. In contrast, researchers observed in vitro experiments the fusion of stem cells and differentiated muscle cells, which could point towards a potential repair mechanism: Muscle repair may not be mediated by transdifferentiation of stem cells into muscle cells, but rather by fusion of stem and muscle cell. Doing so, vitality of the “sick” cell might be improved. In a second study, Max-Planck researchers investigated whether stem cells might contribute to the repair of heart tissue after myocardial infarction. They showed that after injection of stem cells isolated from skeletal muscles or of heart muscle cells which had be risen from embryonic stem cells, that at least in an animal model heart function can be improved. The positive effect most likely is based on a mechanism, in which growth stimulating substances are released into the damaged heart tissue by the injected cells.
  • Plasticity of newt Cardiomyocytes

    2006 Borchardt, Thilo; Kostin, Sawa
    The mammalian heart is not able to regenerate lost cardiac tissue after substantial injuries, instead the heart is repaired by scar formation. Newts and Zebrafish however are able to fully regenerate their hearts without scarring. On of the current projects at the Max Planck Institute for Heart and Lung Research is to understand, how cardiac regeneration takes place in non-mammalian vertebrates. This could provide new approaches that stimulate regenerative pathways in the human heart.

2005

  • Cell differentiation and proliferation during development and regeneration

    2005 Braun, Thomas
    The general research concept of the department of cardiac development and remodelling is characterized by two strategies: (i) a better understanding of processes that lead to proliferation of organ typical precursor cells and their coordinated differentiation during organ development and regeneration; (ii) development of pre-clinical models in which knowledge gained in approach (i) can be used to enable, improve and accelerate tissue regeneration in particular of the heart. Individual research projects are part of this concept and contained in either of these themes. Yet, it is clear that both themes overlap and that such a separation is rather artificial. Nevertheless it might help to distinguish between mostly basic and more applied scientific approaches, which hold a direct medical impact.
  • The role of stem cells in regeneration and repair of organs

    2005 Belema Bedada, Fikru; Heil, Matthias
    The Max-Planck-Institute for Heart and Lung Research in Bad Nauheim focusses on research on the processes being responsible for regeneration and repair of organs such as the heart. Previous studies had shown that stem cells might play an important role. In one of their projects scientists therefore investigated the potential of adult and embryonal stem cells to differentiate into completely developed tissue cells such as skeletal muscle or heart muscle cells. Data show that the use of specific differention factors indeed induces cell programmes which lead to the expression of typical muscle-cell specific factors. However, stem cells could not completely be transfered into muscle cells. In contrast, researchers observed in vitro experiments the fusion of stem cells and differentiated muscle cells, which could point towards a potential repair mechanism: Muscle repair may not be mediated by transdifferentiation of stem cells into muscle cells, but rather by fusion of stem and muscle cell. Doing so, vitality of the “sick” cell might be improved. In a second study, Max-Planck researchers investigated whether stem cells might contribute to the repair of heart tissue after myocardial infarction. They showed that after injection of stem cells isolated from skeletal muscles or of heart muscle cells which had be risen from embryonic stem cells, that at least in an animal model heart function can be improved. The positive effect most likely is based on a mechanism, in which growth stimulating substances are released into the damaged heart tissue by the injected cells.

2004

  • Arteriogenesis - A New Concept for Adaptive Vessel Growth After Vascular Occlusions

    2004 Heil, Matthias; Schaper, Wolfgang
    After birth, blood vessel growth is limited to two major processes. The growth of new capillaries by sprouting or intussusception after the emergence of ischemia is called angiogenesis. In contrast, arteriogenesis describes the formation of collateral arteries from a pre-existing arteriolar network after the occlusion of a major artery. It is the only physiologically effective form of vascular growth in the adult organism to compensate for blood flow deficits after arterial occlusions. Physical forces, particularly fluid shear stress, induced by the increased blood velocity due to low distal pressure, and monocytes are triggers of arteriogenesis.
  • Cell differentiation and proliferation during development and regeneration

    2004 Braun, Thomas
    The general research concept of the department of cardiac development and remodelling is characterized by two strategies: (i) a better understanding of processes that lead to proliferation of organ typical precursor cells and their coordinated differentiation during organ development and regeneration; (ii) development of pre-clinical models in which knowledge gained in approach (i) can be used to enable, improve and accelerate tissue regeneration in particular of the heart. Individual research projects are part of this concept and contained in either of these themes. Yet, it is clear that both themes overlap and that such a separation is rather artificial. Nevertheless it might help to distinguish between mostly basic and more applied scientific approaches, which hold a direct medical impact.

2003

  • Arteriogenesis - A New Concept for Adaptive Vessel Growth After Vascular Occlusions

    2003 Heil, Matthias; Schaper, Wolfgang
    After birth, blood vessel growth is limited to two major processes. The growth of new capillaries by sprouting or intussusception after the emergence of ischemia is called angiogenesis. In contrast, arteriogenesis describes the formation of collateral arteries from a pre-existing arteriolar network after the occlusion of a major artery. It is the only physiologically effective form of vascular growth in the adult organism to compensate for blood flow deficits after arterial occlusions. Physical forces, particularly fluid shear stress, induced by the increased blood velocity due to low distal pressure, and monocytes are triggers of arteriogenesis.
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