Pierre A Guertin

McGill University, Montréal, Quebec, Canada

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Publications (57)155.53 Total impact

  • Pierre A Guertin
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    ABSTRACT: Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs-from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS) networks that are involved in the control of ambulation and other stereotyped motor patterns-specifically Central Pattern Generators (CPGs) that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of spinal cord-injured (SCI) should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic SCI patients.
    Frontiers in Human Neuroscience 01/2014; 8:272. · 2.91 Impact Factor
  • Pascal Rouleau, Pierre A Guertin
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    ABSTRACT: Most animal models of contused, compressed or transected spinal cord injury (SCI) require a laminectomy to be performed. However, despite advantages and disadvantages associated with each of these models, the laminectomy itself is generally associated with significant problems including longer surgery and anaesthesia (related post-operative complications), neuropathic pain, spinal instabilities, deformities, lordosis, and biomechanical problems, etc. This review provides an overview of findings obtained mainly from our laboratory that are associated with the development and characterization of a novel murine model of spinal cord transection that does not require a laminectomy. A number of studies successfully conducted with this model provided strong evidence that it constitutes a simple, reliable and reproducible transection model of complete paraplegia which is particularly useful for studies on large cohorts of wild-type or mutant animals - e.g., drug screening studies in vivo or studies aimed at characterizing neuronal and non-neuronal adaptive changes post-trauma. It is highly suitable also for studies aimed at identifying and developing new pharmacological treatments against aging associated comorbid problems and specific SCI-related dysfunctions (e.g., stereotyped motor behaviours such as locomotion, sexual response, defecation and micturition) largely related with 'command centers' located in lumbosacral areas of the spinal cord.
    Current pharmaceutical design 01/2013; · 4.41 Impact Factor
  • Pierre Guertin
    Current pharmaceutical design 01/2013; · 4.41 Impact Factor
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    ABSTRACT: Much like locomotion or micturition, respiration is a rhythmic and stereotyped motor pattern controlled mainly by non-cortical structures including a complex circuit in the brainstem. Because tight regulation of lung ventilation is essential from the beginning of life, it has been presumed that the neural system regulating breathing is fixed, following a genetically predetermined developmental pattern. Here, we review evidence indicating that early life exposure to a non-systemic stress in the form of neonatal maternal separation (NMS) is sufficient to exert sex-specific consequences on the developmental trajectory of this vital homeostatic system that persist well into full maturity. At adulthood, male rats subjected to NMS are hypertensive and show an abnormally high hypoxic chemoreflex that correlates positively with respiratory instability during sleep. The effects are not observed in females. Investigation of the mechanisms this respiratory phenotype have highlighted the importance of 1) neuroendocrine influences on respiratory regulation and 2) stress-related imbalance between inhibitory (GABAergic) and excitatory (glutamatergic) modulation of the neural elements regulating breathing. These results provide new and valuable insight into the origins of respiratory disorders related to neural control dysfunction such as sleep disordered breathing.
    Current pharmaceutical design 01/2013; · 4.41 Impact Factor
  • Lisa McKerracher, Pierre Guertin
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    ABSTRACT: Spinal cord injury (SCI) often results in permanent paralysis because there is little spontaneous repair. Neuronal injury in the central nervous system (CNS) causes breakage of axonal connections, release of myelin, inflammation and cell death at the lesion site. Many factors contribute to the failure of spontaneous repair after SCI, including the presence of growth inhibitory proteins in myelin, the inflammatory environment of the injured CNS, and the resulting signaling cascades that result in over-activation of Rho, a signaling switch in neurons and axons. In this review, we provide a general overview of growth inhibition in the CNS, and show evidence that most growth inhibitory proteins signal through a common intracellular pathway. Rho is a convergent signal for growth inhibition, and also for signaling some of the secondary consequences of inflammation after SCI. We review the preclinical evidence that targeting Rho is an effective way to stimulate axon regeneration and functional recovery in preclinical animal models. In the last part of the review, we describe the creation of Cethrin, a new investigational drug, and summarize the results of the Phase I/IIa clinical study to examine the safety, tolerability and efficacy of Cethrin in patients with acute SCI. We conclude with some insight for future clinical studies.
    Current pharmaceutical design 01/2013; · 4.41 Impact Factor
  • Inge Steuer, Pascal Rouleau, Pierre A Guertin
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    ABSTRACT: Although research on neural tissue repair has made enormous progress in recent years, spinal cord injury remains a devastating condition for which there is still no cure. In fact, recent estimates of prevalence in the United States reveal that spinal cord injury has undergone a five-fold increase in the last decades. Though, it has become the second most common neurological problem in North America after Alzheimer's disease. Despite modern trauma units and intensive care treatments, spinal cord injury remains associated with several comorbid conditions and unbearable health care costs. Regular administration of a plethora of symptomatic drug treatments aimed at controlling related-secondary complications and life-threatening problems in chronic spinal cord-injured patients has recently been reported. This article provides a thorough overview of the main drug classes and products currently used or in development for chronic spinal cord injury. Special attention is paid to a novel class of drug treatment designed to provide a holistic solution for several chronic complications and diseases related with spinal cord injury. There is clear evidence showing that that new class can elicit 'on-demand' episodes of rhythmic and stereotyped walking activity in previously completely paraplegic animals and may consequently constitute a simple therapy against several physical inactivity-related comorbid problems. Understanding further pharmacological approaches to chronic spinal cord injury may improve both life expectancy and overall quality of life while reducing unsustainable cost increases associated with this debilitation condition.
    Current pharmaceutical design 01/2013; · 4.41 Impact Factor
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    Pierre A Guertin
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    ABSTRACT: This article provides a perspective on major innovations over the past century in research on the spinal cord and, specifically, on specialized spinal circuits involved in the control of rhythmic locomotor pattern generation and modulation. Pioneers such as Charles Sherrington and Thomas Graham Brown have conducted experiments in the early twentieth century that changed our views of the neural control of locomotion. Their seminal work supported subsequently by several decades of evidence has led to the conclusion that walking, flying, and swimming are largely controlled by a network of spinal neurons generally referred to as the central pattern generator (CPG) for locomotion. It has been subsequently demonstrated across all vertebrate species examined, from lampreys to humans, that this CPG is capable, under some conditions, to self-produce, even in absence of descending or peripheral inputs, basic rhythmic, and coordinated locomotor movements. Recent evidence suggests, in turn, that plasticity changes of some CPG elements may contribute to the development of specific pathophysiological conditions associated with impaired locomotion or spontaneous locomotor-like movements. This article constitutes a comprehensive review summarizing key findings on the CPG as well as on its potential role in Restless Leg Syndrome, Periodic Leg Movement, and Alternating Leg Muscle Activation. Special attention will be paid to the role of the CPG in a recently identified, and uniquely different neurological disorder, called the Uner Tan Syndrome.
    Frontiers in Neurology 01/2012; 3:183.
  • Roth-Visal Ung, Pascal Rouleau, Pierre A Guertin
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    ABSTRACT: Chronic spinal cord injury may be complicated by weight loss, muscle atrophy, and bone loss. The authors identified a combination pharmacotherapy using buspirone, carbidopa, and L-DOPA (BCD) that elicits bouts of locomotor-like movements in spinal cord-transected (Tx) mice. They then evaluated the effects of 8 weeks of treadmill training in Tx mice that received BCD or BCD + clenbuterol, a monoaminergic agent with anabolic properties, on locomotor function, muscle atrophy, adipose tissue loss, and bone density measures. Induced locomotor movement, adipose tissue, skeletal muscle, and femoral bone properties were compared in unoperated control mice, operated controls (untreated, untrained Tx mice), and 2 groups of treated, trained Tx mice (Tx + BCD, Tx + BCD + clenbuterol) that also received training. BCD- and BCD + clenbuterol-treated mice showed comparable levels of locomotor movements that significantly improved over time. Soleus muscle mass and soleus and extensor digitorum longus cross-sectional area significantly increased in both groups of BCD-treated mice, with greater effects in BCD + clenbuterol-treated animals. Fiber type conversion, adipose tissues, bone mineral density, and content were reduced in all Tx groups compared with unoperated control mice. These findings suggest that locomotor movement and muscle properties can be restored to near-normal levels after several weeks of BCD treatment, regular training, and clenbuterol in completely paraplegic animals.
    Neurorehabilitation and neural repair 12/2011; 26(4):385-94. · 4.28 Impact Factor
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    Pierre A. Guertin
    09/2011; , ISBN: 978-953-307-969-1
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    P Rouleau, P A Guertin
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    ABSTRACT: Community-based, cross-sectional study. This study aimed at examining and comparing the pharmacological treatments administered to traumatic and nontraumatic spinal-cord-injured patients (TSCI, NTSCI).Setting:The Interval Rehabilitation Center, Trois-Rivieres, Province of Quebec, Canada. Medical records from a cohort of 175 chronic spinal-cord-injured patients (94 TSCI and 81 NTSCI individuals) were thoroughly studied. More than 19 classes and more than 300 drugs were found to be administered to SCI patients. Among them, drugs against bowel and bladder problems, blood clot or deep venous thrombosis, cardiovascular problems, depression or anxiety, stomach acidity, infections, pain, inflammation, sleeping problems and vitamin deficiency were the most commonly used (between 35 and 66% of all SCI patients). Differences between groups were found specifically for antidepressants and anxiolytics used mainly by TSCI patients whereas bisphosphonates, bronchodilators, lipid regulators and anti-inflammatory drugs were used mainly by NTSCI patients. The results revealed an unexpectedly large number of drugs that are prescribed to both groups of SCI patients. Given the existence of between-group differences and known risks of drug-drug interactions, it is suggested that recommendations for each group should be made to carefully examine either the necessity or the effectiveness of each treatment as well as the possibility of developing alternative strategies based on physical activity, nutrition and lifestyle to eventually reduce, hopefully, the number of pharmacological treatments administered to these individuals.
    Spinal Cord 02/2011; 49(2):186-95. · 1.90 Impact Factor
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    Pascal Rouleau, Edouard Ayoub, Pierre A Guertin
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    ABSTRACT: Objective: Differences between traumatic (TSCI) and non-traumatic (NTSCI) spinal cord-injured patients with comparable geographical and socio-economical background have rarely been studied. The objective was to examine and compare a set of epidemiological, clinical, and functional characteristics in TSCI and NTSCI patients. Methods: This is a community-based, cross-sectional study of medical records from a cohort of one hundred and seventy-five (175) chronic spinal cord-injured patients (94 TSCI and 81 NTSCI individuals) who were treated at the Interval Rehabilitation Center located in Trois-Rivieres, Province of Quebec, Canada. Results: Clear differences in age, gender, extent and level of injury or associated conditions (also called secondary complications) were found between TSCI and NTSCI patients. Only one (1/81) completely injured patients was identified among the NTSCI group whereas completely injured patients constituted 37.8% of all TSCI patients. The percentage of patients with associated conditions including neurogenic bladder, neurogenic bowel, urinary tract infection, and pressure ulcer problems was significantly greater in TSCI than NTSCI patients. In contrast, a comparable proportion of TSCI and NTSCI patients was experiencing neuropathic pain. Conclusions: Given these differences between groups as well as regional-specific differences reported in studies from some other countries, it may be suggested that therapeutic approaches developed to treat these health problems and so-called associated conditions could be targeted for specific groups and subgroups of spinal cord-injured patients.
    The Open Epidemiology Journal 01/2011; 411(133):133-139.
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    ABSTRACT: The health benefits associated with physical activity-based rehabilitation in patients with no lower-extremity motor function after a spinal cord injury (SCI) is uncertain. The authors assessed signs of efficacy, safety, and utility associated with a novel pharmacological combination therapy to activate central pattern generator (CPG) activity and corresponding locomotor activity in complete thoracic Th9/10-transected mice. Subcutaneous administration 4 times per week for 1 month of 1.5 mg/kg buspirone, 1.5 mg/kg apomorphine, 12.5 mg/kg benserazide, and 50 mg/kg L-DOPA induced episodes of weight-bearing stepping on a treadmill in nonassisted paraplegic mice for 45-minute sessions. Hindlimb muscle cross-sectional area and fiber area values as well as several blood cell constituent levels assessed at 30 days postinjury were positively affected by the combination therapy, as compared with controls. Episodes of locomotion remained effective on each treatment. Femoral bone mineral density loss was not prevented by triple therapy. Although translation of these findings needs further experimentation, similar pharmacological activation of the CPG offers a novel therapeutic target to provide some health benefits in motor-complete SCI patients.
    Neurorehabilitation and neural repair 10/2010; 25(3):234-42. · 4.28 Impact Factor
  • Roth-Visal Ung, Pascal Rouleau, Pierre A Guertin
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    ABSTRACT: Spinal cord injury (SCI) is generally associated with a rapid and significant decrease in muscle mass and corresponding changes in skeletal muscle properties. Although beta(2)-adrenergic and androgen receptor agonists are anabolic substances clearly shown to prevent or reverse muscle wasting in some pathological conditions, their effects in SCI patients remain largely unknown. Here we studied the effects of clenbuterol and testosterone propionate administered separately or in combination on skeletal muscle properties and adipose tissue in adult CD1 mice spinal-cord-transected (Tx) at the low-thoracic level (i.e., induced complete paraplegia). Administered shortly post-Tx, these substances were found to differentially reduce loss in body weight, muscle mass, and muscle fiber cross-sectional area (CSA) values. Although all three treatments induced significant effects, testosterone-treated animals were generally less protected against Tx-related changes. However, none of the treatments prevented fat tissue loss or muscle fiber type conversion and functional loss generally found in Tx animals. These results provide evidence suggesting that clenbuterol alone or combined with testosterone may constitute better clinically-relevant treatments than testosterone alone to decrease muscle atrophy (mass and fiber CSA) in SCI subjects.
    Journal of neurotrauma 06/2010; 27(6):1129-42. · 4.25 Impact Factor
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    P Rouleau, P A Guertin
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    ABSTRACT: Community-based, cross-sectional study.Objectives:This study aimed at examining and comparing biochemical profiles (blood and urine) of traumatic and non-traumatic spinal cord-injured patients (TSCIs vs NTSCIs). The Interval Rehabilitation Center, Trois-Rivieres, Province of Quebec, Canada. Medical records from a cohort of 175 chronic spinal cord-injured patients (94 TSCI and 81 NTSCI individuals) were thoroughly studied. Augmentations over time of red blood cell (erythrocyte), hematocrit and hemoglobin levels were generally found after spinal cord injury (SCI), specifically in NTSCI patients (late vs early chronic). In contrast, although leukocyte levels generally decreased over time after SCI, higher lymphocyte levels were detected only in NTSCI patients (late vs early chronic). Higher total cholesterol, triglyceride, high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), protein and albumin serum levels were generally found over time after SCI, again, specifically in chronic NTSCI patients (late vs early chronic), whereas increased (twofold) nitrite and decreased (twofold) ubilirogen urine levels were found specifically in TSCI individuals (late vs early chronic). Clear differences were reported between subgroups of SCI patients strongly supporting the idea that therapeutic approaches aimed to treat these problems should be specifically designed for each type of patients (that is, NTSCI vs TSCI or early vs late chronic patients).
    Spinal Cord 05/2010; 48(11):819-24. · 1.90 Impact Factor
  • Pierre A Guertin, Roth-Visal Ung, Pascal Rouleau
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    ABSTRACT: Spinal cord injury (SCI) is a neurological condition, for which no cure exists, typically leading to an immediate and irreversible loss of sensory and voluntary motor functions accompanied by significant health problems. We conducted proof-of-concept experiments aimed at assessing efficacy upon oral administration of a novel combination therapy for central pattern generator (CPG) activation and corresponding locomotor movement generation in completely paraplegic animals. Co-administration orally (by gavage) of buspirone, levodopa and carbidopa was found to dose-dependently induce episodes of steady weight-bearing stepping in low-thoracic (Th9/10) spinal cord-transected (Tx) mice (with no other form of assistance or training). Robust hindlimb stepping with weight-bearing capabilities was induced with the tri-therapy but not with clinically relevant doses of these compounds administered separately. These results provide evidence suggesting that this drug combination may be ideally suited to constitute a first-in-class therapy (CPG activator) for locomotor activity induction in chronic SCI individuals, given that efficacy was shown using commercially available brain-permeable small molecules, already known as safe for the treatment of various neurological indications.
    Biotechnology Journal 03/2010; 5(4):421-6. · 3.71 Impact Factor
  • R V Ung, N P Lapointe, P Rouleau, P A Guertin
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    ABSTRACT: Experiments in a mouse model of complete paraplegia. To evaluate the effect of non-assisted treadmill training on motor recovery and body composition in completely spinal cord-transected mice. Laval University Medical Center, Neuroscience Unit, Quebec City, Quebec, Canada. Following a complete low-thoracic (Th9/10) spinal transection (Tx), mice were divided into two groups that were either untrained or trained with no assistance. Training consisted of placing the mice during 15 min with no further intervention (that is no tail pinching or body weight support) on a motorized treadmill (8-10 cm s(-1)) five times per week for 5 weeks. Locomotor performances were assessed weekly in both groups using two complementary locomotor rating scales. After 5 weeks, all mice were killed and adipose tissue, soleus, and extensor digitorum longus muscles were dissected for analyses. No significant difference in locomotor performances or in muscle fibre type conversion was found between trained and untrained mice. In contrast, body weight, adipose tissue, whole muscle, and individual fibre cross-sectional area (CSA) values were significantly lower in trained compared with untrained animals. Non-assisted treadmill training in these conditions did not improve motor performances and contributed to further accentuate body composition changes post-Tx, suggesting that assistance provided manually, robotically, or pharmacologically may be key to spinal learning and recovery of locomotor function and body composition.
    Spinal Cord 02/2010; 48(10):750-5. · 1.90 Impact Factor
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    Pierre A Guertin
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    ABSTRACT: The global pharmaceutical industry is facing unprecedented challenges that are increasingly influenced by financial, political, demographical and ecological issues. As shown by the significant reduction of new drug applications or NDAs (U.S. Food and Drug Administration-approved new molecular entities) in recent years, the industry is profoundly affected by the increasing cost of development of new drugs, the large number of existing drugs that have begun to go off patent (reduced revenues), increasingly stringent regulations and corresponding increased development time. As a response, we have created a technological platform aimed at accelerating the development of new drug treatments for central nervous system indications. It allows a rapid identification of leads and drug candidates suitable for clinical development based upon a novel in vivo drug screening and hypothesis-driven approach that reduces the time of drug discovery and development. Furthermore, the platform is adapted to specifically identify synergistic (or new) effects induced by combination products with known molecular entities rather than with new molecular entities which reduces risks and costs of development. In less than five years, we have identified with minimal investment, two (2) combination product candidates for functional recovery after spinal cord injury that are suitable for preclinical and clinical development. These results provide evidence suggesting that it is feasible with alternative approaches and small research facilities to efficiently identify leads and drug candidates and, thus, to provide the industry with new drug treatments suitable for clinical development.
    The Open Conference Proceedings Journal. 01/2010; 110(137):137-140.
  • Pierre A Guertin
    Biotechnology Journal 09/2009; 4(8):1124-31. · 3.71 Impact Factor
  • Pierre A Guertin, Inge Steuer
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    ABSTRACT: In the central nervous system (CNS), central pattern generators (CPGs) are generally considered as specialized networks that can produce oscillatory motor output in the absence of any oscillatory input. For instance, respiration and mastication are among the critical biological functions well known to be controlled by such specialized networks. Several other CPGs have also been found specifically in the spinal cord. Among them, the CPG for locomotion is probably the most extensively studied rhythm- and pattern-generating network of the CNS. Other, less completely understood CPGs have also been associated with the control of scratching, micturition, and ejaculation. This review provides a brief update on CPG organization and function in the spinal cord and focuses on similarities and differences between these networks and their pharmacological modulation.
    Journal of Neuroscience Research 04/2009; 87(11):2399-405. · 2.97 Impact Factor
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    ABSTRACT: Dopamine (DA) is well-recognized for its determinant role in the modulation of various brain functions. DA was also found in in vitro isolated invertebrate preparations to activate per se the central pattern generator for locomotion. However, it is less clear whether such a role as an activator of central neural circuitries exists in vertebrate species. Here, we studied in vivo the effects induced by selective DA receptor agonists and antagonists on hindlimb movement generation in mice completely spinal cord-transected (Tx) at the low-thoracic level (Th9/10). Administration of D1/D5 receptor agonists (0.5-2.5 mg kg(-1), i.p.) was found to acutely elicit rhythmic locomotor-like movements (LMs) and non-locomotor movements (NLMs) in untrained and non-sensory stimulated animals. Comparable effects were found in mice lacking the D5 receptor (D5KO) whereas D1/D5 receptor antagonist-pretreated animals (wild-type or D5KO) failed to display D1/D5 agonist-induced LMs. In contrast, administration of broad spectrum or selective D2, D3 or D4 agonists consistently failed to elicit significant hindlimb movements. Overall, the results clearly show in mice the existence of a role for D1 receptors in spinal network activation and corresponding rhythmic movement generation.
    The Journal of Physiology 03/2009; 587(Pt 7):1499-511. · 4.38 Impact Factor

Publication Stats

521 Citations
155.53 Total Impact Points

Institutions

  • 2013
    • McGill University
      Montréal, Quebec, Canada
  • 2004–2013
    • Laval University
      • Faculté de Médecine
      Québec, Quebec, Canada
  • 2010–2011
    • Centre Hospitalier Universitaire de Québec (CHUQ)
      Québec, Quebec, Canada
  • 2007
    • Centre hospitalier de l'Université de Montréal (CHUM)
      Montréal, Quebec, Canada
  • 1998–2006
    • IT University of Copenhagen
      København, Capital Region, Denmark