Dr. Dr. Melanie Königshoff

Research program for repairing diseased lungs

Melanie Königshoff, MD, PhD is head of the new research unit “Lung Repair and Regeneration” at Helmholtz Zentrum München. Her major objectives: to elucidate and specifically control the repair processes of the lung in order to treat lung diseases. At the same time she is committed to education and training. “Successful research not only requires good ideas and researchers with lots of experience, but also well-trained, motivated young scientists,” said the researcher. 

Dr. Dr. Melanie Königshoff. Image: HMGU

“We currently still do not know whether the diseased adult lung can regenerate itself,” said Melanie Königshoff. In her new position as head of the new research unit “Lung Repair and Regeneration” and her W2 professorship at Ludwig-Maximilians-Universität München, she hopes to find answers to these questions.

Exploiting regeneration processes

“When you consider the constant interaction of our lungs with our environment and their response to stimuli, their plasticity and their ability to adapt, it is only a matter of time until we elucidate the underlying mechanisms of these repair processes that can be applied to treat diseases,” Königshoff added. The medical need is huge: There is currently no causal treatment for chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) and physicians are unable to halt COPD or IPF progression. Both diseases progress inexorably and rapidly lead to a severe impairment in the quality of life. Lung transplants are currently the only curative intervention, however, urgently needed donor organs are limited.

Endogenous and exogenous processes

“Novel regenerative approaches to combat lung disease are promising “, Königshoff said. Before she was promoted to her new position, Melanie Königshoff headed a young investigator group at the Comprehensive Pneumology Center (CPC) / Institute of Lung Biology and Disease (iLBD) that focused on endogenous lung repair processes. This research approach was made possible through an ERC Starting Grant. The main question of her research: How can cells of the lung epithelium contribute to induce lung repair; which signaling pathways must be activated to achieve this? “Now we are expanding our focus to include regenerative pharmacology in order to test new substances, so-called small molecules, in cell-based regeneration assays and human 3D tissue cultures (3D-LTCs).” In addition, the research unit is increasingly focusing on the role of viral infections, which represent a common environmental challenge of the lungs and which strongly influence repair processes. Within the new Unit, Melanie Königshoff is also eager to explore novel exogenous approaches to lung regeneration. Bioengineering lung tissue likely requires a symbiosis of biology and engineering. One idea would be to construct an artificial lung scaffold outside the body and to seed it with healthy cells derived from the eventual transplant recipient, thus obviating the need for immunosuppressive drugs which are known to cause complications in current lung transplant patients.

Successful in the network

Melanie Königshoff’s ideas did not occur to her by chance. Parallel to her training as a physician she has sought for years to find answers to questions of lung (patho)biology. Following an MD supervised by Professor Alfred Pingoud and a PhD supervised by Professor Werner Seeger, Giessen and several research stays abroad, Melanie Königshoff joined the team of Professor Oliver Eickelberg, director of the CPC/iLBD, in Munich as a young investigators group leader. During this time, she had the “unique opportunity to build up her own laboratory and at the same time take part in establishing the CPC”. Königshoff also appreciates the excellent collaborative opportunities and the chance to carry out translational research. She is strongly engaged in training of young scientists. Since 2010 she has been program director of the Helmholtz Research School “Lung Biology and Disease” and has advanced the further development of the activities of the graduate program. In particular, she focuses on the training of MDs and MD/PhDs within the framework of the Physician Scientists Program at the CPC. “The future of translational lung research will be marked by the joint training and further collaboration of scientists from diverse backgrounds in medicine, pharmacology, biology and engineering,” said Königshoff. With her new research unit, she is now taking a step forward in this direction.

Publications

Klee S et al., WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts. Sci Rep. 2016 Feb 12;6:20547. doi: 10.1038/srep20547.
http://www.ncbi.nlm.nih.gov/pubmed/26867691

Spanjer AI et al., TGF-β-induced profibrotic signaling is regulated in part by the WNT receptor Frizzled-8. FASEB J. 2016 May;30(5):1823-35. doi: 10.1096/fj.201500129. Epub 2016 Feb 5.
http://www.ncbi.nlm.nih.gov/pubmed/26849959

Uhl FE et al., Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures. Eur Respir J. 2015. DOI: 10.1183/09031936.00183214. http://www.ncbi.nlm.nih.gov/pubmed/25929950

Mutze K et al., Enolase 1 (ENO1) and protein disulfide-isomerase associated 3 (PDIA3) regulate Wnt/β-catenin-driven trans-differentiation of murine alveolar epithelial cells. Dis Model Mech. 2015. DOI: 10.1242/dmm.019117. http://www.ncbi.nlm.nih.gov/pubmed/26035385

Kneidinger N et al., Activation of the WNT/β-catenin pathway attenuates experimental emphysema. Am J Respir Crit Care Med. 2011. DOI: 10.1164/rccm.200910-1560OC. http://www.ncbi.nlm.nih.gov/pubmed/20889911