Prof. Dr. Martina Schmidt

About Martina Schmidt

I am heading the group of Molecular Pharmacology, currently composed of about 40 staff members including 3 principal investigators, 5 technicians, 2 lectures, 1 FSE Research Fellow, 2 post-docs and a spin-off company. My enthusiasm for education is appreciated by many students, PhD students, post-doc trainees. In 2007, I received the Organon prize for pharmacology. Currently I am member of the executive board FIGON and program committee FIGON Dutch Medicine Days, Fellow of British Pharmacological Society, FBPhS, and serve as member of EUPHAR.

I started my university career in Biology, then performed my PhD in Physiological Chemistry before I specialized as Molecular Pharmacologist. I received the “Venia legendi” in Pharmacology & Toxicology both in Germany and the Netherlands. After research periods in UK and the Netherlands, I moved as a Rosalind Franklin Fellow to the Faculty of Science and Engineering, University of Groningen.

In 2007, I received the Organon prize for pharmacology. Currently I am member of the executive board FIGON and program committee FIGON Dutch Medicine Days, Fellow of British Pharmacological Society, FBPhS, and serve as member of EUPHAR.

My translational research focuses on the molecular pharmacological aspects of the development and course of chronic inflammatory diseases. My motivation for this research focus is very personal, I truly believe that research in the field of translational pharmacology is clustered around molecular partners in defined subcellular compartments (signalosomes) that enables cells to exert highly specialized tasks. Devastating diseases, e.g. cancer, type-II diabetes mellitus, Alzheimers’s dementia, heart failure, asthma, COPD, and infection diseases are associated with defective or derailed signaling processes, and research into the control of these processes clearly is of great public and social importance as well.

Currently my research focus lies on chronic inflammatory disorders, and I focus nowadays on experimental models of COPD and related lung disorders, Alzheimer, Parkinson and microbial infections. I have successfully undertaken the effort to link the themes to defined subcellular compartments (signalosomes). I linked novel signaling pathways from membrane receptors towards the recently identified PLC- isoform, the cAMP sensor Epac. I defined novel and exciting functions of the cytoskeleton driver cofilin, a signal node clearly linked to microbe invasion. I linked this novel clusters to inflammation, remodeling next to the repair of the epithelial barrier and epithelial-to-mesenchymal transition as a mechanism driving fibrosis.

To achieve such goals I strongly believe in multidisciplinary proceeding, and a continuous search for new collaborations with local, national and international groups. My research is funded by scientific organizations (NWO, DFG, others) and the industry, we hold patents ("COPD"; ref: 4/2QG32/3). National and international feasibility is high, and the societal impact has been recognized by charity organizations such as Lung Foundation Netherlands and Alzheimer Foundation Netherlands. Interest in respiratory diseases is further fostered within the spin-off company Aquilo. I study the impact of air pollution (and cigarette smoke) on multi-protein complexes and their function in experimental lung models. I combine novel techniques like fluorescence energy transfer technology, precision cut tissue slices, organoids, 2D/3D cultures, metabolomics and “omics” to study inflammation and fibrosis. Particularly using fluorescence energy transfer technology combined with precision cut lung slice technologies and expression profiling, I provided evidence that oxidative stress profoundly alters expression profiles of cAMP sensors.

Selected publications

1. Schmidt M, Evellin S, Oude Weernink PA, vom Dorp F, Rehmann H, Lomasney JW, Jakobs KH (2001). A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase. Nature Cell Biol 3, 1020-1024. Cited:357
   I described a novel signaling pathways from membrane receptors towards the recently identified PLC-ε isoform, and the cAMP sensor Epac. This pathway has turned out to of central importance in the regulation of inflammation, remodeling next to the repair of the epithelial barrier and epithelial-to-mesenchymal transition as a mechanism driving fibrosis as shown in studies in experimental models of COPD and related lung disorders.
2. Han L, Stope MB, López de Jesús M, Oude Weernink PA, Urban M, Wieland T, Rosskopf D, Jakobs KH, Schmidt M (2007). Phospho-cofilin directly interacts with and stimulates receptor-controlled phospholipase D1. EMBO J 26, 4189-4202. Cited:106
   I defined novel and exciting functions of the cytoskeleton driver cofilin, a signal node clearly linked to microbe invasion.
3. Schmidt M, Dekker F, Maarsingh H (2013). Exchange protein directly activated by cAMP (Epac): a multidomain cAMP mediator in the regulation of diverse biological functions. Pharmacol Rev 65, 670-709. Cited:225
   State-of-the art overview about the achievements of Epac’s impact on chronic inflammatory disorders.
4. Oldenburger A Roscioni SS, Jansen E Menzen MH, Halayko AJ, Timens W, Meurs H, Maarsingh H, Schmidt M (2012). Anti-inflammatory role of the cAMP effectors Epac and PKA: implications in chronic obstructive pulmonary disease. PlosOne, 7, e31574. Cited:68
   Linkage of Epac to inflammation in experimental models of COPD.
5. Oldenburger A, Timens W, Bos S, Smit M, Smrcka Laurent CL, Cao JJ, Hylkema M, Meurs H, Maarsingh H, Lezoualc'h F, Schmidt M (2014) Epac1 and Epac2 are differentially involved in inflammatory and remodeling processes induced by cigarette smoke. FASEB. J. 28, 4617-4628. Cited:26
   Linkage of Epac to inflammation, remodeling and fibrosis in experimental models of COPD.
6. Roscioni SS, Maarsingh H, Elzinga, CRS, Schuur J, Menzen M, Halayko AJ, Meurs H, Schmidt, M. (2011). Epac as a novel effector of airway smooth muscle relaxation. J.Cell.Mol.Med., 15, 1551-1563. Cited:77
   Linkage of Epac to airway muscle tone in experimental models of COPD.
7. Oldenburger A, Poppinga WJ, Kos F, de Bruin HG, Rijks WF, Heijnk I, Timens W, Meurs H, Maarsingh H, Schmidt M (2014). A-kinase anchoring proteins contribute to loss of E-cadherin and bronchial epithelial barrier by cigarette smoke. Am. J. Physiol. 306,C585-597. Cited:41
   Linkage of Epac to epithelial barrier in experimental models of COPD.
8. Zuo H, Heijink IH, van der Veen CHTJ, Hesse L, Faber KN, Poppinga WJ, Maarsingh H, Nikolaev VO, Schmidt M. A-kinase anchoring proteins diminish TGF-β1 / cigarette smoke-induced epithelial-to-mesenchymal transition. Cells. 2020 Feb 3;9(2):356.
   Linkage of Epac to epithelial-to-mesenchymal transition and fibrosis in experimental models of COPD.
9. Zuo H, Bing H, Poppinga WJ, Ringnalda L, Kistemaker LME, Halayko AJ, Gosens R, Nikolaev VO, Martina Schmidt (2018) Cigarette smoke upregulates PDE3 and PDE4 to decrease cAMP in airway cells. Brit J Pharmacol, 175(14):2988-3006.Cited:8
   Using fluorescence energy transfer technology combined with precision cut lung slice technologies and expression profiling, I provided evidence that oxidative stress profoundly alters expression profiles of cAMP sensors. Studies were performed in experimental models of COPD.
10. Zuo H, Faiz A, van den Berge M, Mudiyanselage SNHR, Borghuis T, Timens W, Nikolaev VO, Burgess JK, Schmidt M. (2020). Cigarette smoke exposure alters phosphodiesterases in human structural lung cells. Am J Physiol Lung Cell Mol Physiol. 2020 Jan 1;318(1):L59-L64.
    Using fluorescence energy transfer technology combined with precision cut lung slice technologies and expression profiling, I provided evidence that oxidative stress profoundly alters expression profiles of cAMP sensors. Studies were performed in samples from COPD patients.