Dirk Adriaensen emeritus with assignment

Research Dirk Adriaensen

Research team

Expertise

Experimental lung research focused on structure (from organ to molecular level), function and potential pathology of strongly innervated groups of neuroendocrine cells (neuroepithelial bodies; NEBs) in the airway epithelium of lab animal and human lungs. Development of an ex vivo lung slice model for functional 'live cell imaging' of NEBs, but also of virtually any other cell and tissue type in the lungs. We could already demonstrate that NEBs and their microenvironment serve as sensory airway receptors for both chemical and mechanical stimuli, but also as a specific niche for a unique population of postnatal airway epithelial stem cells. Research now focusses on the silencing and potential activation mechanisms of these intriguing stem cells, and on their possible link with the development of small cell lung carcinomas.

Modular confocal microscopy platform with light sheet illumination. 01/05/2016 - 30/04/2020

Abstract

The application concerns an innovative microscopy platform for visualizing cells, tissue specimen and living small model organisms in three dimensions at unprecedented speed and with excellent resolution and contrast. As a unique feature, the platform is equipped with a light-sheet module, which is based on an orthogonal configuration of laser-generated, micrometer-thin plane illumination and sensitive one-shot detection. Seamless integration with confocal modalities enables imaging the same sample from the micro- to the mesoscale. The device has a broad application radius in the neurosciences domain inter alia for studying neurodegeneration and -regeneration (e.g. whole brain imaging, optogenetics); but it also has direct utility in various other fields such as cardiovascular research (e.g. plaque formation and stability), plant developmental research (e.g. protein localization during plant growth) and ecotoxicology (e.g. teratogenicity and developmental defects in zebrafish). Furthermore, its modular construction will enable adaptation and targeted expansion for future imaging needs.

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  • Research Project

Expression and role of dipeptidyl peptidases and related peptidases in acute lung injury. 01/01/2015 - 31/12/2018

Abstract

Acute lung injury remains the third major cause of mortality worldwide, and it is assumed that excessive inflammatory responses could be involved. The precise role of dipeptidyl peptidases (DPPs; a family of enzymes that cleave off dipeptides from the amino terminus of peptides) in the pathophysiology of acute lung injury is poorly understood. Taken broadly, the DPP family consists of DPPIV, fibroblast activation protein alpha (FAP), prolyl oligopeptidase (PREP), DPP8 and DPP9. DPPIV inhibitors are used in the treatment of diabetes type 2, but evidence for other roles of DPPIV is also emerging. Despite a presumed role of individual peptidases in lung disease, knowledge on DPPs in acute lung injury remains limited. Previously, we have shown that DPPIV inhibitors protect against lung ischemia-reperfusion induced injury. Apart from that, we discovered that DPP9 has a role in macrophage activation, which is an important component of acute lung injury. The current project aims to explore the hypothesis that DPPIV, DPP9 and related peptidases play a role in the pathophysiology of acute lung injury. We will study the expression of DPPs in both an infectious and a non-infectious mouse model of acute lung injury. Subsequently, we will determine the effect of DPPIV inhibition on the outcome, and will assess whether DPPs have a role in lung macrophages. We will compare the animal findings with measurements in human tissue to study the translational potential of our results.

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  • Research Project

Infrastructure for soft and delicate matter imaging. 26/04/2012 - 31/12/2017

Abstract

"Soft matter" is anything from a well-defined term. It is used to represent a broad class of materials including colloids, polymers, biological specimens and biomaterials. Although the use of such materials becomes increasingly important in nanotechnology, a successful implementation can only be reached through a thorough structural investigation at the nanolevel. Electron microscopy is the most widely used technique to study inorganic (nano)materials, even at the atomic scale. Such investigations however, are far from straightforward when soft matter is considered. Therefore this application aims at an environmental scanning electron microscope as well as a cryo ultramicrotome.

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  • Research Project

Study of the proportion of pulmonary neuro-epithelial bodies in vagal reflex activities based on stimuli in the respiratory tracts. 01/01/2011 - 31/12/2012

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

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  • Research Project

Identification of functional molecular pathways in the pulmonary neuroepithelial body microenvironment: Laser capture microdissection and gene expression study. 01/01/2011 - 31/12/2011

Abstract

This project aims at identifying pathways that are involved in the normal function of NEBs in postnatal lungs. The NEB microenvironment will be dissected in large numbers via advanced laser capture microdissection and will be used for gene expression analysis.

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  • Research Project

Putative noxious effects of the insecticide deltamethrin on the enteric nervous system in mammals. 01/08/2010 - 31/05/2011

Abstract

The insecticide deltamethrin, a powerful synthetic pyrethroid, acts toward insects by ingestion or contact, altering normal neuronal function. Deltamethrin is known to modify sodium channel activities and intracellular calcium concentrations in neurons. It is of moderately high toxicity in mammals. Deltamethrin will increasingly be used in agriculture, resulting in an increased exposure of man to deltamethrin in time. This project focuses on the effects of the prolonged oral congestion of non-toxic doses of deltamethrin on the intrinsic and extrinsic innervation of the mammalian gastrointestinal tract. The study comprises morphological (multiple immunofluorescence and in situ hybridisation techniques) and microscopic (fluorescence or confocal laser scanning microscopy) techniques to detect effects of deltamethrin on viability and chemical coding of neurons in the gastrointestinal tract and in spinal and nodose ganglia of mouse and rat. Quantitative RT-PCR will be used to verify whether semi-quantitative changes occur at the mRNA level. Cultures of isolated vagal, spinal or enteric neurons will be applied to study in vitro the effects of deltamethrin in time on neurons using classic intracellular electrophysiological recording and optical recording. The obtained data will be helpful to recognize, prevent and treat putative noxious effects of a prolonged exposure to non-toxic doses of deltamethrin.

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CLCI - High end infrastructure for confocal live cell imaging. 22/07/2010 - 28/04/2015

Abstract

This project represents a formal research agreement between UA and on the other hand the Flemish Public Service. UA provides the Flemish Public Service research results mentioned in the title of the project under the conditions as stipulated in this contract.

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  • Research Project

Biomedical Microscopic Imaging and in-vivo Bio-Imaging (EGAMI). 01/02/2010 - 31/12/2014

Abstract

This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

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  • Research Project

Study of the proportion of pulmonary neuro-epithelial bodies in vagal reflex activities based on stimuli in the respiratory tracts. 01/01/2009 - 31/12/2010

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  • Research Project

In situ analysis of the interactions between pulmonary neuroepithelial bodies and a population of stem cell-like airway epithelial cells: a possible link with small cell lung carcinogenesis. 01/01/2008 - 31/12/2011

Abstract

For the planned studies, the mouse was chosen as a model, because we have been able to gather for this species a considerable amount of morphological and neurochemical data related to pulmonary NEBs and the associated vCE cells, and of course also because of the additional possibilities that are created for the use of transgenic and knock-out (KO) mouse models. Also, we will be able to use the in situ mouse lung-slice model that was recently developed in our lab (Pintelon et al. 2005), and which will provide unique possibilities for the proposed project via molecular live cdl imaging. Finally, it is interesting to realise that SCLC mouse models (and all other relevant genetic mouse models) can easily be combined with this lung-slice model.

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  • Research Project

Bidirectional communication between the enteric nervous system and elements of the immune system in inflammatory gastrointestinal disorders. 01/01/2008 - 31/12/2011

Abstract

In this project animal models were used to study the interaction between neuronal components of the GI tract and elements of the immune system, more particularly mast cells and dendritic cells, during inflammation. This interaction appears to play an important role in the inflammatory response and might offer a better insight for the observed hyperexcitability of afferent components of the enteric nervous system during gastrointestinal inflammation. This project will primarily focus on the possible role of cortistatin and urocortines in this interaction.

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  • Research Project

Oxidative stress and inflammation: critical role in cardiovascular and infectious diseases. 01/07/2007 - 30/06/2011

Abstract

Oxidative stress is a pivotal factor in inflammatory processes, but research is hampered by the difficulties to detect free radicals, i.e. reactive oxygen species (ROS) and nitric oxide (NO¿). Objectives of this project include: 1/ validation of methods for in vitro quantification of ROS and NO¿ using electron paramagnetic resonance (EPR); 2/ visualisation of their cellular origin using modern microscopic imaging and 3/ application of these novel platforms to study ROS in inflammatory processes with focus on macrophage function, intracellular infections, atherosclerosis and heart failure.

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    Study of the intestinal mucosal response and oxidative stress on the course of Giardia duodenalis infections in laboratory animal models. 01/10/2006 - 30/09/2007

    Abstract

    A new research initiative will study the micro-aerophilic intestinal protozoa Giardia intestinalis. This pathogen has developed anti-oxidative defense mechanisms to withstand the oxygen tension in tissues and organs, e.g. via oxidation of cellular thiols, superoxide-dismutase and possibly other mechanisms. The importance of these mechanisms is illustrated by the fact that current therapeutics (nitro-compounds) exert their action via selective increase of oxidative stress. The research plan involves the following steps: 1. development/optimization of in vitro culture method for trophozoites 2. establishment of conditions for induction of cyst formation, 3. development of a suitable laboratory animal model, 4. influence of oxidative stress on the in vitro and in vivo survival by in situ quantification of oxidative/antioxidative phenomena 5. evaluation of new molecules in the in vitro and in vivo models 6. evaluation of disinfectants for inactivation of cysts in drinking water 7. interaction of the parasite with intestinal lining (pathology, inflammation, e.a..)

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    Fluorescent live cell imaging and CFP/YFP based FRET analysis of the interaction and tetramerization of the subunits of 'silent' ion channels. 01/01/2004 - 31/12/2007

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    In vitro physiological and functional morphologic study of neurotransmitter receptors related to pulmonary neuroepithelial bodies. 01/05/2003 - 30/04/2005

    Abstract

    The project should allow us to investigate the presence of neurotransmitter receptors on pulmonary neuroepithelial bodies and their complex selective innervation. Among other methods, we will use our recently developed in vitro lung slice model, which allows the microscopic visualisation of ph~siological parameters by means of the confocal UltraVIEW Live Cell Imager. We plan to concentrate on the neurotransmitters that we previously demonstrated to be present in the system.

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    • Research Project

    Functional morphological and physiological study of pulmonary neuroepithelial bodies: in vivio and in vitro experimental study of the influence of intermittent hypoxia and of environmental parameters. 01/01/2003 - 31/12/2006

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    • Research Project

    Is glutamate a neurotransmitter in nerve terminals in the lung? Possible link with neuroepithelial bodies and other airway receptors. 01/01/2003 - 30/09/2003

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      • Research Project

      Research in the field of Biomedical applications of fluorescence microscopic techniques. 01/10/2001 - 30/09/2009

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      • Research Project

      "Starting" fund for faculty (ZAP): interdisciplinary research professorship (ZAP-BOF) "Biomedical applications of fluorescence microscopic techniques". 01/10/2001 - 30/09/2004

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      • Research Project

      The pulmonary neuroendocrine system in neuronal nitric oxide synthase gene knockout mice. 01/01/2001 - 31/12/2004

      Abstract

      The proposed functional morphological study of pulmonary NEBs in nNOS gene knockout mice should enable us to evaluate the possibility of a direct involvement of intrinsic pulmonary nitrergic neurons in the peripheral oxygen perception via NEBs. The newest two-photon laser scanning microscope will be used for the microscopical visualisation of physiological reactions of NEBs in vitro

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      • Research Project

      Functional morphological study of the interaction between neuronal and non-neuronal elements in relation to oesophageal motility. 01/01/2001 - 31/12/2004

      Abstract

      The main aims of this project are the study of 1. the correlation between morphological and physiological features of intrinsic esophageal neurons and 2. the role of interstitial cells of Cajal in this part of the gastrointestinal tract.

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      • Research Project

      Morphological visualisation of physiological characteristics of pulmonary neuropithelial bodies (NEBs) using two-pohoton laser scanning microscopy. 01/01/2001 - 31/12/2002

      Abstract

      The project proposal should allow us to elaborate an experimental setup for the direct microscopial visualisation of physiological parameters of pulmonary NEBs and nearby intrinsic neurons. A two-photon laser scanning microscopial setup, which was recently installed in our lab as the first in Belgium, will be used. Almost no data are available today, since the study involves an essentially new concept.

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        • Research Project

        Detection and distribution pattern of neuropeptide-receptors in the enteric nervous system of mammals, using fluorescent-labeled ligands. 01/01/1998 - 31/12/1999

        Abstract

        Using so-called "fluopeptides" this study not only tries to determine the distribution pattern of several neuropeptides-receptors in the gastro-intestinal tract, but also to study the kinetics of these receptors under well-defined circumstances.

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          • Research Project

          Synthesis of bio-active substances in neuro-epithelial endocrine cells by means of in situ hybridization. 01/05/1995 - 30/04/1997

          Abstract

          Using non-radioactive labeled mRNA- or oligonucleotideprobes, in situ hybridization is applied to gain a better insight in the panel of bio-active substances that can be produced by the neuroepithelial endocrine cells in the respiratory system of vertebrates.

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            • Research Project