Prof. Dr. Miguel A. Alejandre Alcázar

Associated Principal Investigator, Assistant Professor, Research Group Leader – University Hospital of Cologne

Assistant Prof. Dr. Miguel A. Alejandre Alcázar

Principal Investigator, Research Group Leader

+49 (0)221 478 96876


Uniklinik Köln

Kerpener Strasse 62

50937 Köln

Perinatal injury and the origins of cardiopulmonary aging

Life-saving respiratory support (e.g mechanical ventilation or oxygen supply) and metabolic disorders during a critical window of lung development induce chronic lung diseases, including bronchopulmonary dysplasia (BPD). The changes in lung structure and function early on are similar to those seen in adult’s chronic lung diseases, e.g. emphysema, COPD, and pulmonary arterial hypertension. To date, the molecular mechanisms underlying neonatal chronic lung diseases remain poorly understood. The molecular, cellular, and structural characteristics of neonatal chronic lung diseases are closely related to hallmarks of aging, e.g. DNA damage, loss of stemness or matrix remodeling. Early prevention and treatment of neonatal chronic lung disease are of great medical socioeconomic importance to improve neonatal care and to promote lung health. Our research group investigates premature activation of aging-associated processes in the developing and aging lung.

Our research: Dr. Alejandre Alcázar and his research team aim to decipher converging molecular mechanisms by which mechanical ventilation, oxygen, and obesity interfere with normal lung development and induce lung injury. Chronic lung diseases are the second most common cause of death worldwide and preventive or curative treatments are lacking. Accumulating evidence suggest that adverse influences during development induce chronic injury or sensitize the lung for chronic lung diseases later in life. The perinatal medical challenges along with the clinical significance of chronic lung diseases highlight the urgent need to unravel converging pathways and to identify novel targets in order to develop preventive and therapeutic strategies.

Our successes: Our research group demonstrated that exposure of the developing lung to prolonged hyperoxia, mechanical ventilation, malnutrition or obesity leads to neonatal chronic lung disease. Inflammatory processes along with dysregulation of transcription factors (e.g. Klf4) are key mechanisms of aberrant lung development and neonatal chronic lung disease. These findings are closely related to hallmarks of aging, including altered nutrient sensing, loss of stemness, DNA damage response (DDR), and matrix remodeling.

Our goals: The research team has identified molecular mechanisms that are central in aberrant lung development and early origins of chronic lung disease. Our goal is to decipher molecular pathways that regulate aging processes in the developing lung and how disruption of those signaling networks via transcription factors could promote lung aging. To this end, our research group will pursue three aims: first, we will study an animal model of a premature aged mouse lung using a cell-specific deletion of DNA excision repair protein Ercc1. Second, we will decipher converging signaling pathways of neonatal chronic lung disease, adult chronic lung disease, and naturally aged lungs. Finally, we will target specific novel molecules and transcription factors to prevent premature aging and neonatal chronic lung disease. The Alcázar group has the vision to develop new strategies to promote lung health early in life in order to prevent chronic lung disease.

Our methods/techniques: Researchers in the Alcázar group employ a variety of techniques, ranging from primary cell lines and precision cut lung slices to genetic modified mice and neonatal animal models (hyperoxia/ventilation- and obesity-induced neonatal lung injury) along with state-of-the-art approaches in systems biology to elucidate the molecular mechanisms of neonatal lung disease. 


Figure 1: Exposure of the neonatal lung to hyperoxia leads to lung growth arrest and neonatal chronic lung disease (nCLD). These structural changes are evident beyond infancy and similar to emphysema, an adult chronic lung disease.

Figure 2: Schematic overview of perinatal adverse influences and possible mechanisms by which lung development is disrupted and chronic lung disease is induced.

EXTERNAL Cooperations
  • Prof. Dr. Denise Al Alam, Lundquist Institute, UCLA, USA
  • Prof. Dr. Philip Hansbro, Centre for Inflammation, Centenary Institute & University of Technology Sydney, School of Life Sciences, Faculty of Science, Sydney, NSW Australia
  • Prof. Dr. Soni Savai Pullamsetti, MPI HLR Bad Nauheim, Cardiopulmonary Institute, Universities of Gießen and Marburg Lung Center (UGMLC)
  • Prof. Dr. Marlene Rabinovitch, Stanford University, USA
  • Prof. Dr. Stefan Worgall, Pediatric Pneumology, Weill Cornell University, NY, USA
  • Prof. James Priest and Dr. Daniela Zanetti, Stanford Cardiovascular Institute, Stanford University, USA