(see English version below)

Forschungsinteresse

Unsere Arbeitsgruppe hat sich auf die translationale Forschung mit dem Fokus auf die Mechanismen, die akute und chronische Entzündungen kontrollieren, insbesondere auf die vielfältigen Funktionen von Akute-Phase-Proteinen dabei spezialisiert. Vor allem interessiert uns das Akute-Phase-Protein α1-Antitrypsin, das einen der wichtigsten menschlichen Serinproteaseinhibitoren darstellt und klinisch als Medikament zur Behandlung von Patienten mit dem schweren erblichen Alpha1-Antitrypsin-Mangel eingesetzt wird. Eines unserer Forschungsziele ist es, die Therapie mit Alpha1-Antitrypsin zu verbessern und die Behandlung von Patienten mit dem Alpha1-Antitrypsin-Mangel zu unterstützen. Wir stehen in enger Zusammenarbeit mit den Alpha1-Patientenorganisationen in Deutschland und in anderen Ländern. 
Vor einigen Jahren haben wir und auch andere Forscher den Nachweis erbracht, dass α1-Antitrypsin nicht nur bei der Entstehung des Emphysems, sondern auch bei der Entstehung von anderen chronisch entzündlichen Erkrankungen, wie entzündlichen Darmerkrankungen, Haut- und Lebererkrankungen, Diabetes und auch Krebs, eine Rolle spielt. Kürzlich wurde publiziert, dass  α1-Antitrypsin den Eintritt des SARS-CoV-2 Coronavirus in die Zellen reguliert und dass sich höhere Plasmaspiegel von α1-Antitrypsin positiv bei Patienten mit COVID-19 auswirken.
α1-Antitrypsin interagiert mit anderen Molekülen, was zu Oxidation, Spaltung, oder anderen Modifikationen und zu Komplexbildungen, erhöhter Biosynthese und zur Polymer-Selbstassemblierung von α1-Antitrypsin führen kann. Einige dieser Veränderungen resultieren in einer erworbenen α1-Antitrypsin-Defizienz; jedoch könnten auch molekulare Formen mit neuen biologischen Aktivitäten entstehen, die eine prognostische Bedeutung haben könnten und/oder die Wirksamkeit einer Therapie vorhersagen könnten. Wir entwickeln spezifische Antikörper-basierte Tests um diese modifizierten molekularen Formen, vor allem Polymere oder proteolytischen Spaltprodukte von α1-Antitrypsin im Gewebe und in biologischen Flüssigkeiten zu detektieren.
Offenkundig gibt es noch vieles über Akute-Phase-Proteine, wie α1-Antitrypsin, und ihre Rolle im gesunden Körper und bei Krankheiten zu lernen.

Research Interests

Our research group specializes in translational research with a focus on the mechanisms controlling acute and chronic inflammation with particular focus on the multiple roles played by acute phase proteins. We are specifically interested in α1-antitrypsin, an acute phase glycoprotein that is one of the major inhibitors of human serine proteases and clinically used as a drug to treat emphysema patients with severe inherited alpha1-antitrypsin deficiency. Our aim is to improve therapy with α1-antitrypsin and to support care of patients with inherited Alpha1 Deficiency. We are in a close collaboration with Alpha1- Patient organization in Germany and other countries.
Since years, we and other researchers have provided evidence that α1-antitrypsin plays a role not only in emphysema development but also in other chronic inflammatory diseases, such as inflammatory bowel diseases, skin diseases and liver diseases, diabetes, cancer, among others. Recently, it was published that α1-antitrypsin regulates the entry of SARS-CoV-2 corona virus into cells and that higher plasma levels of α1-antitrypsin are beneficial for COVID-19 patients.
α1-antitrypsin interacts with other molecules, which may lead to its oxidation, degradation, complex formation, increased biosynthesis, self-assembly, or additional modifications. Some of these changes result in acquired deficiency of native protein; however, they may also generate new molecular forms with potent biological activities, which may have prognostic value and/or predict therapeutic response in various diseases. Therefore, since more than 25 years, we are interested in the conformational polymorphism of α1-antitrypsin that determined the complexity of its biological functions. We are developing specific antibody-based immunological assays to detect modified molecular forms of α1-antitrypsin, specifically polymers and cleaved forms, in human tissues and biological fluids.  
It is clear that there is much more to learn about acute phase proteins, like α1-antitrypsin, and their roles on health and disease. 

Forschungsprojekte / Research Projects

• Studies in primary cell co-cultures and in biomaterials from patient cohorts on the role and molecular mechanisms of proteases-anti-proteases and their interactions with immune cells in lung cancer
• Analysis of a potential immunomodulatory role of alpha1-antitrypsin in COVID-19 
• Studies on the suitibility of acute phase proteins as biomarkers for different diseases
• Development of immunoassays to detect native, polymeric and cleaved (C-terminal fragment) forms of alpha1-antitrypsin in tissues and biological fluids from healthy individuals and patients with chronic inflammatory disease with and without inherited alpha1-antitrypsin deficiency
• Studies on the role of acute phase proteins, specifically alpha1-antitrypsin, in acute and chronic obstructive pulmonary and liver diseases
• Specific role of alpha1-antitrypin in cystic fibrosis: molecular studies in 3D epithelial cell cultures
• Studies on the improvements of therapy with alpha1-antitrypsin: validation of novel recombinant forms of protein and exploration of novel application routes of alpha1-antitrypsin administration

Unsere Klinik gehört zu den Alpha-1-Centern, zu denen sich Ärzte in Praxen und Kliniken zusammengeschlossen haben um durch ihre Expertise die bestmögliche Betreuung von Patienten mit Alpha-1-Antitrypsinmangel zu erreichen.

Frau Dr. Sabina Janciauskiene-Wallmark hat in den letzten Jahren Kollaborationen mit Kolleginnen und Kollegen in Deutschland, Schweden, England, USA, Italien, Polen und Holland etabliert. Sie arbeitet eng mit der Alpha1-Patientenorganisation in Deutschland und mit deren Partnerorganisationen in anderen Ländern zusammen. In Hannover gibt es auf dem Campus der MHH zahlreiche gemeinsame Projekte, u. a. mit dem Institut für Pathologie, der Kinderklinik, der Biophysikalischen Chemie, der Gastroenterologie/Hepatologie/Endokrinologie, der Transfusionsmedizin und der Experimentellen HTTG Chirurgie und mit dem Fraunhofer ITEM.

Die Forschungsprojekte werden finanziell unterstützt durch das Deutsche Zentrum für Lungenforschung (DZL), Grifols, Excellgene, Kamada und CSL Behring.

Our Department belongs to the Alpha-1-Centers. These centers were built by physicians in private practice and clinics to combine their expertise and to achieve optimal care for patients with alpha1-antitrypsin deficiency.

Dr. Sabina Janciauskiene-Wallmark established collaborations with collegues in Germany, Sweden, England, USA, Italy, Poland and The Netherlands in the recent years. She is in close connection to the German Alpha1 patient organisation and the foreign partner organisations. In Hannover, several collaborative projects exist together with different clinics and institutes of the Hannover Medical School and the Fraunhofer ITEM.

The research projects are funded by the German Center of Lung Research (DZL), Grifols, Excellgene, Kamada und CSL Behring.

Jüngste Publikationen / Recent Publications

2023

• Plasma levels of alpha1-antitrypsin-derived C-terminal peptides in PiMM and PiZZ COPD patients. Friedemann R. Börner, Urszula Lechowicz, Sabine Wrenger, Beatriz Martinez-Delgado, Beata Olejnicka, Tobias Welte, Joanna Chorostowska-Wynimko, Michael Kiehntopf, Sabina Janciauskiene. ERJ Open Res, in press.
• NAFLD and AATD are two diseases with unbalanced lipid metabolism: similarities and differences. Perez-Luz S, Matamala N, Gomez-Mariano G, Janciauskiene S, Martínez-Delgado B. Biomedicines. 2023 Jul 12;11(7):1961. doi: 10.3390/biomedicines11071961
• Mice inflammatory responses to inhaled aerosolized LPS: effects of various forms of human alpha1-antitrypsin. Sivaraman K, Wrenger S, Liu B, Schaudien D, Hesse C, Gomez-Mariano G, Perez-Luz S, Sewald K, DeLuca D, Wurm MJ, Pino P, Welte T, Martinez-Delgado B, Janciauskiene S. J Leukoc Biol. 2023 Jan 10;113(1):58-70. doi: 10.1093/jleuko/qiac004. PMID: 36822165
• Editorial: Acute phase proteins as biomarkers and therapeutics in acute and chronic inflammatory conditions. Stanke F, Janciauskiene S, Olejnicka B. Front Pharmacol. 2023 Feb 2;14:1145990. doi: 10.3389/fphar.2023.1145990. eCollection 2023. PMID: 36817143 
• Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses. Kamp JC, Kappe NN, Moro CF, Fuge J, Kuehnel MP, Wrenger S, Welte T, Hoek BV, Jonigk DD, Khedoe PPSJ, Strnad P, Björnstedt M, Stolk J, Janciauskiene S, Nemeth A. Int J Mol Sci. 2023 Jan 27;24(3):2485. doi: 10.3390/ijms24032485. PMID: 36768808
• Pleural CD14+ monocytes/macrophages of healthy adolescents show a high expression of metallothionein family genes. Schukfeh N, Liu B, DeLuca DS, Tumpara S, Nikolin C, Immenschuh S, Ure BM, Kuebler JF, Welte T, Viemann D, Janciauskiene SM, Vieten G.Eur J Immunol. 2023 Jan;53(1):e2250019. doi: 10.1002/eji.202250019. Epub 2022 Nov 18.PMID: 36321537
• Analysis of CF patient survival confirms STAT3 as a CF-modifying gene with changing impact over time. Dunsche I, Raddatz EL, Ismer H, Hedtfeld S, Tamm S, Moser S, Kontsendorn J, Tümmler B, Janciauskiene S, Dittrich AM, Stanke F. Hum Mol Genet. 2023 Jan 27;32(4):543-550. doi: 10.1093/hmg/ddac221. PMID: 36048831

2022

• Plasma markers of COVID-19 severity: a pilot study. Beimdiek J, Janciauskiene S, Wrenger S, Volland S, Rozy A, Fuge J, Olejnicka B, Pink I, Illig T, Popov A, Chorostowska J, Buettner FFR, Welte T. Respir Res. 2022 Dec 13;23(1):343. doi: 10.1186/s12931-022-02272-7. PMID: 36514048
• Indirect effect of alpha-1-antitrypsin on endotoxin-induced IL-1β secretion from human PBMCs. Janciauskiene S, Tumpara S, Schebb NH, Buettner FFR, Mainka M, Sivaraman K, Immenschuh S, Grau V, Welte T, Olejnicka B. Front Pharmacol. 2022 Sep 30;13:995869. doi: 10.3389/fphar.2022.995869. eCollection 2022. PMID: 36249781
• Loss of Serpina1 in Mice Leads to Altered Gene Expression in Inflammatory and Metabolic Pathways. Meghadri SH, Martinez-Delgado B, Ostermann L, Gomez-Mariano G, Perez-Luz S, Tumpara S, Wrenger S, DeLuca DS, Maus UA, Welte T, Janciauskiene S. Int J Mol Sci. 2022 Sep 9;23(18):10425. doi: 10.3390/ijms231810425. PMID: 36142337
• Lung Adenocarcinoma Cell Sensitivity to Chemotherapies: A Spotlight on Lipid Droplets and SREBF1 Gene. Gründing AR, Schneider MA, Richtmann S, Kriegsmann M, Winter H, Martinez-Delgado B, Varona S, Liu B, DeLuca DS, Held J, Wrenger S, Muley T, Meister M, Welte T, Janciauskiene S. Cancers (Basel). 2022 Sep 14;14(18):4454. doi: 10.3390/cancers14184454. PMID: 36139614
• Determination of free heme in stored red blood cells with an apo-horseradish peroxidase-based assay. Vijayan V, Greite R, Schott S, Doricic J, Madyaningrana K, Pradhan P, Martens J, Blasczyk R, Janciauskiene S, Immenschuh S. Biol Chem. 2022 Sep 5;403(11-12):1091-1098. doi: 10.1515/hsz-2022-0184. Print 2022 Nov 25. PMID: 36054292
• A Morphomolecular Approach to Alveolar Capillary Dysplasia. Kamp JC, Neubert L, Ackermann M, Stark H, Plucinski E, Shah HR, Janciauskiene S, Bergmann AK, Schmidt G, Welte T, Haverich A, Werlein C, Braubach P, Laenger F, Schwerk N, Olsson KM, Fuge J, Park DH, Schupp JC, Hoeper MM, Kuehnel MP, Jonigk DD. Am J Pathol. 2022 Aug;192(8):1110-1121. doi: 10.1016/j.ajpath.2022.05.004. Epub 2022 May 29. PMID: 35649494
• The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients. Sark AD, Fromme M, Olejnicka B, Welte T, Strnad P, Janciauskiene S, Stolk J. Biomolecules. 2022 Feb 28;12(3):380. doi: 10.3390/biom12030380. PMID: 35327571
• Transmembrane serine protease 2 is a prognostic factor for lung adenocarcinoma. Schneider MA, Richtmann S, Gründing AR, Wrenger S, Welte T, Meister M, Kriegsmann M, Winter H, Muley T, Janciauskiene S. Int J Oncol. 2022 Apr;60(4):39. doi: 10.3892/ijo.2022.5329. Epub 2022 Feb 25. PMID: 35211754
• Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency. Fromme M, Schneider CV, Pereira V, Hamesch K, Pons M, Reichert MC, Benini F, Ellis P, H Thorhauge K, Mandorfer M, Burbaum B, Woditsch V, Chorostowska-Wynimko J, Verbeek J, Nevens F, Genesca J, Miravitlles M, Nuñez A, Schaefer B, Zoller H, Janciauskiene S, Abreu N, Jasmins L, Gaspar R, Gomes C, Schneider KM, Trauner M, Krag A, Gooptu B, Thorburn D, Marshall A, Hurst JR, Lomas DA, Lammert F, Gaisa NT, Clark V, Griffiths W, Trautwein C, Turner AM, McElvaney NG, Strnad P. Gut. 2022 Feb;71(2):415-423. doi: 10.1136/gutjnl-2020-323729. Epub 2021 Feb 25. PMID: 33632708 
• Matrix metalloproteinase-13 is fully activated by neutrophil elastase and inactivates its serpin inhibitor, alpha-1 antitrypsin: Implications for osteoarthritis. Wilkinson DJ, Falconer AMD, Wright HL, Lin H, Yamamoto K, Cheung K, Charlton SH, Arques MDC, Janciauskiene S, Refaie R, Rankin KS, Young DA, Rowan AD. FEBS J. 2022 Jan;289(1):121-139. doi: 10.1111/febs.16127. Epub 2021 Jul 30.PMID: 34270864 
• Acute Phase Proteins as Early Predictors for Immunotherapy Response in Advanced NSCLC: An Explorative Study. Schneider MA, Rozy A, Wrenger S, Christopoulos P, Muley T, Thomas M, Meister M, Welte T, Chorostowska-Wynimko J, Janciauskiene S. Front Oncol. 2022 Jan 31;12:772076. doi: 10.3389/fonc.2022.772076. eCollection 2022. PMID: 35174082

2021

• α1-Antitrypsin attenuates acute rejection of orthotopic murine lung allografts. Nakagiri T, Wrenger S, Sivaraman K, Ius F, Goecke T, Zardo P, Grau V, Welte T, Haverich A, Knöfel AK, Janciauskiene S. Respir Res. 2021 Nov 17;22(1):295. doi: 10.1186/s12931-021-01890-x. PMID: 34789247
• Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by α-1 Antitrypsin. Tumpara S, Gründing AR, Sivaraman K, Wrenger S, Olejnicka B, Welte T, Wurm MJ, Pino P, Kiseljak D, Wurm FM, Janciauskiene S. Int J Mol Sci. 2021 Jul 26;22(15):7941. doi: 10.3390/ijms22157941. PMID: 34360706 
• Application of alpha1-antitrypsin in a rat model of veno-arterial extracorporeal membrane oxygenation. Edinger F, Schmitt C, Koch C, McIntosh JM, Janciauskiene S, Markmann M, Sander M, Padberg W, Grau V. Sci Rep. 2021 Aug 4;11(1):15849. doi: 10.1038/s41598-021-95119-y. PMID: 34349162 
• Pulmonary transplantation of alpha-1 antitrypsin (AAT)-transgenic macrophages provides a source of functional human AAT in vivo. Janosz E, Hetzel M, Spielmann H, Tumpara S, Rossdam C, Schwabbauer M, Kloos D, von Kaisenberg C, Schambach A, Buettner FFR, Janciauskiene S, Lachmann N, Moritz T. Gene Ther. 2021 Jul 19. doi: 10.1038/s41434-021-00269-3. Online ahead of print. PMID: 34276045 
• Alpha1-antitrypsin counteracts heme-induced endothelial cell inflammatory activation, autophagy dysfunction and death. Madyaningrana K, Vijayan V, Nikolin C, Aljabri A, Tumpara S, Korenbaum E, Shah H, Stankov M, Fuchs H, Janciauskiene S, Immenschuh S. Redox Biol. 2021 Jun 30;46:102060. doi: 10.1016/j.redox.2021.102060. Online ahead of print. PMID: 34246063 
• Serum macrophage migration inhibitory factor as a potential biomarker to evaluate therapeutic response in patients with allergic asthma: an exploratory study. Zhu H, Yan S, Wu J, Zhang Z, Li X, Liu Z, Ma X, Zhou L, Zhang L, Feng M, Geng Y, Zhang A, Janciauskiene S, Xu A. J Zhejiang Univ Sci B. 2021 Jun 15;22(6):512-520. doi: 10.1631/jzus.B2000555. PMID: 34128374 
• Polymerization of misfolded Z alpha-1 antitrypsin protein lowers CX3CR1 expression in human PBMCs. Tumpara S, Ballmaier M, Wrenger S, König M, Lehmann M, Lichtinghagen R, Martinez-Delgado B, Korenbaum E, DeLuca D, Jedicke N, Welte T, Fromme M, Strnad P, Stolk J, Janciauskiene S. Elife. 2021 May 18;10:e64881. doi: 10.7554/eLife.64881. PMID: 34002692 
• Effect of Alpha-1 Antitrypsin on CFTR Levels in Primary Human Airway Epithelial Cells Grown at the Air-Liquid-Interface. Stanke F, Janciauskiene S, Tamm S, Wrenger S, Raddatz EL, Jonigk D, Braubach P. Molecules. 2021 Apr 30;26(9):2639. doi: 10.3390/molecules26092639. PMID: 33946490 
• Commercial α1-antitrypsin preparations markedly differ in their potential to inhibit the ATP-induced release of monocytic interleukin-1β. Agné A, Richter K, Padberg W, Janciauskiene S, Grau V. Pulm Pharmacol Ther. 2021 Jun;68:102020. doi: 10.1016/j.pupt.2021.102020. Epub 2021 Mar 25. PMID: 33774155  
• Potential Roles of Acute Phase Proteins in Cancer: Why Do Cancer Cells Produce or Take Up Exogenous Acute Phase Protein Alpha1-Antitrypsin? Janciauskiene S, Wrenger S, Günzel S, Gründing AR, Golpon H, Welte T. Front Oncol. 2021 Feb 19;11:622076. doi: 10.3389/fonc.2021.622076. eCollection 2021. PMID: 33680966 
• A Novel Mouse Monoclonal Antibody C42 against C-Terminal Peptide of Alpha-1-Antitrypsin. Tumpara S, Korenbaum E, Kühnel M, Jonigk D, Olejnicka B, Davids M, Welte T, Martinez-Delgado B, Janciauskiene S. Int J Mol Sci. 2021 Feb 21;22(4):2141. doi: 10.3390/ijms22042141. PMID: 33670003 
• Alpha-1 antitrypsin deficiency impairs lung antibacterial immunity in mice. Ostermann L, Maus R, Stolper J, Schütte L, Katsarou K, Tumpara S, Pich A, Mueller C, Janciauskiene S, Welte T, Maus UA. JCI Insight. 2021 Feb 8;6(3):140816. doi: 10.1172/jci.insight.140816. PMID: 33554955 

2020

• Genetic information from discordant sibling pairs points to ESRP2 as a candidate trans-acting regulator of the CF modifier gene SCNN1B. Becker T, Pich A, Tamm S, Hedtfeld S, Ibrahim M, Altmüller J, Dalibor N, Toliat MR, Janciauskiene S, Tümmler B, Stanke F. Sci Rep. 2020 Dec 31;10(1):22447. doi: 10.1038/s41598-020-79804-y. PMID: 33384439 
• Plasma Acute Phase Proteins as Predictors of Chronic Lung Allograft Dysfunction in Lung Transplant Recipients. Janciauskiene S, Royer PJ, Fuge J, Wrenger S, Chorostowska-Wynimko J, Falk C, Welte T, Reynaud-Gaubert M, Roux A, Tissot A, Magnan A. J. Inflamm Res. 2020 Nov 30;13:1021-1028. doi: 10.2147/JIR.S272662. eCollection 2020. PMID: 33299339
• Post-Translational Modifications of Circulating Alpha-1-Antitrypsin Protein. Lechowicz U, Rudzinski S, Jezela-Stanek A, Janciauskiene S, Chorostowska-Wynimko J. Int J Mol Sci. 2020 Dec 2;21(23):9187. doi: 10.3390/ijms21239187. PMID: 33276468. Review. 
• The Distribution of Alpha-1 Antitrypsin Genotypes Between Patients with COPD/Emphysema, Asthma and Bronchiectasis. Veith M, Tüffers J, Peychev E, Klemmer A, Kotke V, Janciauskiene S, Wilhelm S, Bals R, Koczulla AR, Vogelmeier CF, Greulich T. Int J Chron Obstruct Pulmon Dis. 2020 Nov 6;15:2827-2836. doi: 10.2147/COPD.S271810. eCollection 2020. PMID: 33192056
• TLR4 Signaling by Heme and the Role of Heme-Binding Blood Proteins. Janciauskiene S, Vijayan V, Immenschuh S. Front Immunol. 2020 Aug 27;11:1964. doi: 10.3389/fimmu.2020.01964. eCollection 2020. PMID: 32983129. Review. 
• The Delivery of α1-Antitrypsin Therapy Through Transepidermal Route: Worthwhile to Explore. Tumpara S, Martinez-Delgado B, Gomez-Mariano G, Liu B, DeLuca DS, Korenbaum E, Jonigk D, Jugert F, Wurm FM, Wurm MJ, Welte T, Janciauskiene S. Front Pharmacol. 2020 Jul 3;11:983. doi: 10.3389/fphar.2020.00983. eCollection 2020. PMID: 32719598 Free PMC article. 
• The Beneficial Effects of Antioxidants in Health And Diseases. Janciauskiene S. Chronic Obstr Pulm Dis. 2020 Jul;7(3):182-202. doi: 10.15326/jcopdf.7.3.2019.0152. PMID: 32558487 Review. 
• Alpha1-antitrypsin protects lung cancer cells from staurosporine-induced apoptosis: the role of bacterial lipopolysaccharide. Schwarz N, Tumpara S, Wrenger S, Ercetin E, Hamacher J, Welte T, Janciauskiene S. Sci Rep. 2020 Jun 12;10(1):9563. doi: 10.1038/s41598-020-66825-w. PMID: 32533048
• New cis-Acting Variants in PI*S Background Produce Null Phenotypes Causing Alpha-1 Antitrypsin Deficiency. Matamala N, Gomez-Mariano G, Perez JA, Baladrón B, Torres-Durán M, Michel FJ, Saez R, Hernández-Pérez JM, Belmonte I, Rodriguez-Frias F, Blanco I, Strnad P, Janciauskiene S, Martinez-Delgado B. Am J Respir Cell Mol Biol. 2020 Oct;63(4):444-451. doi: 10.1165/rcmb.2020-0021OC. PMID: 32515985 
• Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers. Schneider CV, Hamesch K, Gross A, Mandorfer M, Moeller LS, Pereira V, Pons M, Kuca P, Reichert MC, Benini F, Burbaum B, Voss J, Gutberlet M, Woditsch V, Lindhauer C, Fromme M, Kümpers J, Bewersdorf L, Schaefer B, Eslam M, Bals R, Janciauskiene S, Carvão J, Neureiter D, Zhou B, Wöran K, Bantel H, Geier A, Dirrichs T, Stickel F, Teumer A, Verbeek J, Nevens F, Govaere O, Krawczyk M, Roskams T, Haybaeck J, Lurje G, Chorostowska-Wynimko J, Genesca J, Reiberger T, Lammert F, Krag A, George J, Anstee QM, Trauner M, Datz C, Gaisa NT, Denk H, Trautwein C, Aigner E, Strnad P; European Alpha-1 Liver Study Group. Gastroenterology. 2020 Aug;159(2):534-548.e11. doi: 10.1053/j.gastro.2020.04.058. Epub 2020 May 4. PMID: 32376409 
• Proteomic characterization of idiopathic pulmonary fibrosis patients: stable versus acute exacerbation. Carleo A, Landi C, Prasse A, Bergantini L, D'Alessandro M, Cameli P, Janciauskiene S, Rottoli P, Bini L, Bargagli E. Monaldi Arch Chest Dis. 2020 Apr 30;90(2). doi: 10.4081/monaldi.2020.1231. PMID: 32362107 
• Novel Liquid Biomarker Panels for A Very Early Response Capturing of NSCLC Therapies in Advanced Stages. Janke F, Bozorgmehr F, Wrenger S, Dietz S, Heussel CP, Heussel G, Silva CF, Rheinheimer S, Feisst M, Thomas M, Golpon H, Günther A, Sültmann H, Muley T, Janciauskiene S, Meister M, Schneider MA. Cancers (Basel). 2020 Apr 12;12(4):954. doi: 10.3390/cancers12040954. PMID: 32290637
• Protocol for the EARCO Registry: a pan-European observational study in patients with α1-antitrypsin deficiency. Greulich T, Altraja A, Barrecheguren M, Bals R, Chlumsky J, Chorostowska-Wynimko J, Clarenbach C, Corda L, Corsico AG, Ferrarotti I, Esquinas C, Gouder C, Hećimović A, Ilic A, Ivanov Y, Janciauskiene S, Janssens W, Kohler M, Krams A, Lara B, Mahadeva R, McElvaney G, Mornex JF, O'Hara K, Parr D, Piitulainen E, Schmid-Scherzer K, Seersholm N, Stockley RA, Stolk J, Sucena M, Tanash H, Turner A, Ulmeanu R, Wilkens M, Yorgancioğlu A, Zaharie A, Miravitlles M. ERJ Open Res. 2020 Mar 2;6(1):00181-2019. doi: 10.1183/23120541.00181-2019. eCollection 2020 Jan. PMID: 32154291 Free PMC article. 
• Does heart surgery change the capacity of α1-antitrypsin to inhibit the ATP-induced release of monocytic interleukin-1β? A preliminary study. Agné A, Richter K, Tumpara S, Sauer AL, Beckert F, Wrenger S, Zakrzewicz A, Hecker A, Markmann M, Koch C, Zajonz T, Sander M, Böning A, Padberg W, Janciauskiene S, Grau V. Int Immunopharmacol. 2020 Apr;81:106297. doi: 10.1016/j.intimp.2020.106297. Epub 2020 Feb 12. PMID: 32062078 
• Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease. Gómez-Mariano G, Matamala N, Martínez S, Justo I, Marcacuzco A, Jimenez C, Monzón S, Cuesta I, Garfia C, Martínez MT, Huch M, Pérez de Castro I, Posada M, Janciauskiene S, Martínez-Delgado B. Hepatol Int. 2020 Jan;14(1):127-137. doi: 10.1007/s12072-019-10007-y. Epub 2019 Dec 13.PMID: 31832977 
• Serum Levels of Alpha1-antitrypsin and Their Relationship With COPD in the General Spanish Population. Janciauskiene S, DeLuca DS, Barrecheguren M, Welte T, Miravitlles M; Scientific Committee; Participating sites and coordinators. Arch Bronconeumol (Engl Ed). 2020 Feb;56(2):76-83. doi: 10.1016/j.arbres.2019.03.001. Epub 2019 May 30.PMID: 31153743 

2019

• Diagnosing Alpha-1-Antitrypsin Deficiency Using A PCR/Luminescence-Based Technology. Veith M, Klemmer A, Anton I, El Hamss R, Rapun N, Janciauskiene S, Kotke V, Herr C, Bals R, Vogelmeier CF, Greulich T. Int J Chron Obstruct Pulmon Dis. 2019 Nov 18;14:2535-2542. doi: 10.2147/COPD.S224221. eCollection 2019. PMID: 31819391
• Clinical Significance of SERPINA1 Gene and Its Encoded Alpha1-antitrypsin Protein in NSCLC. Ercetin E, Richtmann S, Delgado BM, Gomez-Mariano G, Wrenger S, Korenbaum E, Liu B, DeLuca D, Kühnel MP, Jonigk D, Yuskaeva K, Warth A, Muley T, Winter H, Meister M, Welte T, Janciauskiene S, Schneider MA. Cancers (Basel). 2019 Sep 4;11(9):1306. doi: 10.3390/cancers11091306. PMID: 31487965 
• Morphological and molecular motifs of fibrosing pulmonary injury patterns. Jonigk D, Stark H, Braubach P, Neubert L, Shin HO, Izykowski N, Welte T, Janciauskiene S, Warnecke G, Haverich A, Kuehnel M, Laenger F. J Pathol Clin Res. 2019 Oct;5(4):256-271. doi: 10.1002/cjp2.141. Epub 2019 Sep 25. PMID: 31433553 
• SERPINA1 gene polymorphisms in a population-based ALSPAC cohort. DeLuca DS, Poluzioroviene E, Taminskiene V, Wrenger S, Utkus A, Valiulis A, Alasevičius T, Henderson J, Bush A, Welte T, Janciauskiene S, Valiulis A. Pediatr Pulmonol. 2019 Sep;54(9):1474-1478. doi: 10.1002/ppul.24422. Epub 2019 Jul 12. PMID: 31298815 
• Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation. Hamesch K, Mandorfer M, Pereira VM, Moeller LS, Pons M, Dolman GE, Reichert MC, Schneider CV, Woditsch V, Voss J, Lindhauer C, Fromme M, Spivak I, Guldiken N, Zhou B, Arslanow A, Schaefer B, Zoller H, Aigner E, Reiberger T, Wetzel M, Siegmund B, Simões C, Gaspar R, Maia L, Costa D, Bento-Miranda M, van Helden J, Yagmur E, Bzdok D, Stolk J, Gleiber W, Knipel V, Windisch W, Mahadeva R, Bals R, Koczulla R, Barrecheguren M, Miravitlles M, Janciauskiene S, Stickel F, Lammert F, Liberal R, Genesca J, Griffiths WJ, Trauner M, Krag A, Trautwein C, Strnad P; European Alpha1-Liver Study Group. Gastroenterology. 2019 Sep;157(3):705-719.e18. doi: 10.1053/j.gastro.2019.05.013. Epub 2019 May 20. PMID: 31121167 
• SLPI Inhibits ATP-Mediated Maturation of IL-1β in Human Monocytic Leukocytes: A Novel Function of an Old Player. Zakrzewicz A, Richter K, Zakrzewicz D, Siebers K, Damm J, Agné A, Hecker A, McIntosh JM, Chamulitrat W, Krasteva-Christ G, Manzini I, Tikkanen R, Padberg W, Janciauskiene S, Grau V. Front Immunol. 2019 Apr 4;10:664. doi: 10.3389/fimmu.2019.00664. eCollection 2019. PMID: 31019507
• Blood monocyte profiles in COPD patients with PiMM and PiZZ α1-antitrypsin. Stolk J, Aggarwal N, Hochnadel I, Wrenger S, Martinez-Delgado B, Welte T, Yevsa T, Janciauskiene S. Respir Med. 2019 Mar;148:60-62. doi: 10.1016/j.rmed.2019.02.001. Epub 2019 Feb 6. PMID: 30827477 
• The European Alpha-1 Research Collaboration (EARCO): a new ERS Clinical Research Collaboration to promote research in alpha-1 antitrypsin deficiency. Miravitlles M, Chorostowska-Wynimko J, Ferrarotti I, McElvaney NG, O'Hara K, Stolk J, Stockley RA, Turner A, Wilkens M, Greulich T; EARCO Clinical Research Collaboration; Members of the EARCO Clinical Research Collaboration. Eur Respir J. 2019 Feb 14;53(2):1900138. doi: 10.1183/13993003.00138-2019. Print 2019 Feb. PMID: 30765486 No abstract available. 
• Lectin Complement Pathway in Emphysema. Serban KA, Mikosz A, Strange C, Janciauskiene SM, Stolk J, Jonigk D, Sandhaus RA, Petrache I. Am J Respir Crit Care Med. 2019 Mar 1;199(5):659-661. doi: 10.1164/rccm.201807-1380LE. PMID: 30557515 Free PMC article. No abstract available. 
• Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis. Strnad P, Buch S, Hamesch K, Fischer J, Rosendahl J, Schmelz R, Brueckner S, Brosch M, Heimes CV, Woditsch V, Scholten D, Nischalke HD, Janciauskiene S, Mandorfer M, Trauner M, Way MJ, McQuillin A, Reichert MC, Krawczyk M, Casper M, Lammert F, Braun F, von Schönfels W, Hinz S, Burmeister G, Hellerbrand C, Teufel A, Feldman A, Schattenberg JM, Bantel H, Pathil A, Demir M, Kluwe J, Boettler T, Ridinger M, Wodarz N, Soyka M, Rietschel M, Kiefer F, Weber T, Marhenke S, Vogel A, Hinrichsen H, Canbay A, Schlattjan M, Sosnowsky K, Sarrazin C, von Felden J, Geier A, Deltenre P, Sipos B, Schafmayer C, Nothnagel M, Aigner E, Datz C, Stickel F, Morgan MY, Hampe J, Berg T, Trautwein C. Gut. 2019 Jun;68(6):1099-1107. doi: 10.1136/gutjnl-2018-316228. Epub 2018 Aug 1. PMID: 30068662 

2018

• Alpha-1 Antitrypsin Inhibits ATP-Mediated Release of Interleukin-1β via CD36 and Nicotinic Acetylcholine Receptors. Siebers K, Fink B, Zakrzewicz A, Agné A, Richter K, Konzok S, Hecker A, Zukunft S, Küllmar M, Klein J, McIntosh JM, Timm T, Sewald K, Padberg W, Aggarwal N, Chamulitrat W, Santoso S, Xia W, Janciauskiene S, Grau V. Front Immunol. 2018 Apr 25;9:877. doi: 10.3389/fimmu.2018.00877. eCollection 2018. PMID: 29922281 
• The Multifaceted Effects of Alpha1-Antitrypsin on Neutrophil Functions. Janciauskiene S, Wrenger S, Immenschuh S, Olejnicka B, Greulich T, Welte T, Chorostowska-Wynimko J. Front Pharmacol. 2018 Apr 17;9:341. doi: 10.3389/fphar.2018.00341. eCollection 2018. PMID: 29719508 Free PMC article. Review. 
• Liver - master and servant of serum proteome. Kuscuoglu D, Janciauskiene S, Hamesch K, Haybaeck J, Trautwein C, Strnad P. J Hepatol. 2018 Aug;69(2):512-524. doi: 10.1016/j.jhep.2018.04.018. Epub 2018 Apr 28. PMID: 29709680 Review. 
• OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Marchetti C, Swartzwelter B, Gamboni F, Neff CP, Richter K, Azam T, Carta S, Tengesdal I, Nemkov T, D'Alessandro A, Henry C, Jones GS, Goodrich SA, St Laurent JP, Jones TM, Scribner CL, Barrow RB, Altman RD, Skouras DB, Gattorno M, Grau V, Janciauskiene S, Rubartelli A, Joosten LAB, Dinarello CA. Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):E1530-E1539. doi: 10.1073/pnas.1716095115. Epub 2018 Jan 29. PMID: 29378952 Free PMC article. 
• Gene and miRNA expression profiles in PBMCs from patients with severe and mild emphysema and PiZZ alpha1-antitrypsin deficiency. Esquinas C, Janciauskiene S, Gonzalo R, Mas de Xaxars G, Olejnicka B, Belmonte I, Barrecheguren M, Rodriguez E, Nuñez A, Rodriguez-Frias F, Miravitlles M. Int J Chron Obstruct Pulmon Dis. 2017 Nov 29;12:3381-3390. doi: 10.2147/COPD.S145445. eCollection 2017. PMID: 29238183 Free PMC article. 
• Characterization of Novel Missense Variants of SERPINA1 Gene Causing Alpha-1 Antitrypsin Deficiency. Matamala N, Lara B, Gomez-Mariano G, Martínez S, Retana D, Fernandez T, Silvestre RA, Belmonte I, Rodriguez-Frias F, Vilar M, Sáez R, Iturbe I, Castillo S, Molina-Molina M, Texido A, Tirado-Conde G, Lopez-Campos JL, Posada M, Blanco I, Janciauskiene S, Martinez-Delgado B. Am J Respir Cell Mol Biol. 2018 Jun;58(6):706-716. doi: 10.1165/rcmb.2017-0179OC. PMID: 29232161

2017

• Prevalence of comorbidities in COPD patients by disease severity in a German population. Greulich T, Weist BJD, Koczulla AR, Janciauskiene S, Klemmer A, Lux W, Alter P, Vogelmeier CF. Respir Med. 2017 Nov;132:132-138. doi: 10.1016/j.rmed.2017.10.007. Epub 2017 Oct 12. PMID: 29229085 
• Comparison of exercise training responses in COPD patients with and without Alpha-1 antitrypsin deficiency. Jarosch I, Hitzl W, Koczulla AR, Wencker M, Welte T, Gloeckl R, Janciauskiene S, Kenn K. Respir Med. 2017 Sep;130:98-101. doi: 10.1016/j.rmed.2017.07.009. Epub 2017 Jul 15. PMID: 29206641 
• Cardiovascular risk in patients with alpha-1-antitrypsin deficiency. Fähndrich S, Biertz F, Karch A, Kleibrink B, Koch A, Teschler H, Welte T, Kauczor HU, Janciauskiene S, Jörres RA, Greulich T, Vogelmeier CF, Bals R; COSYCONET investigators. Respir Res. 2017 Sep 15;18(1):171. doi: 10.1186/s12931-017-0655-1. PMID: 28915894 Free PMC article. 
• Impact of alpha 1-antitrypsin deficiency and prior augmentation therapy on patients' survival after lung transplantation. Conrad A, Janciauskiene S, Köhnlein T, Fuge J, Ivanyi P, Tudorache I, Gottlieb J, Welte T, Fuehner T. Eur Respir J. 2017 Sep 10;50(3):1700962. doi: 10.1183/13993003.00962-2017. Print 2017 Sep. PMID: 28890438 No abstract available. 
• Alpha1-antitrypsin binds hemin and prevents oxidative activation of human neutrophils: putative pathophysiological significance. Janciauskiene S, Tumpara S, Wiese M, Wrenger S, Vijayan V, Gueler F, Chen R, Madyaningrana K, Mahadeva R, Welte T, Immenschuh S, Chorostowska-Wynimko J. J Leukoc Biol. 2017 Oct;102(4):1127-1141. doi: 10.1189/jlb.3A0317-124R. Epub 2017 Jul 17. PMID: 28716864 
• Exogenous alpha 1-antitrypsin down-regulates SERPINA1 expression. Karadagi A, Johansson H, Zemack H, Salipalli S, Mörk LM, Kannisto K, Jorns C, Gramignoli R, Strom S, Stokkeland K, Ericzon BG, Jonigk D, Janciauskiene S, Nowak G, Ellis ECS. PLoS One. 2017 May 9;12(5):e0177279. doi: 10.1371/journal.pone.0177279. eCollection 2017. PMID: 28486562 Free PMC article. 
• Heme as a Target for Therapeutic Interventions. Immenschuh S, Vijayan V, Janciauskiene S, Gueler F. Front Pharmacol. 2017 Apr 4;8:146. doi: 10.3389/fphar.2017.00146. eCollection 2017. PMID: 28420988 Free PMC article. Review. 
• Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function. Waschki B, Watz H, Holz O, Magnussen H, Olejnicka B, Welte T, Rabe KF, Janciauskiene S. Int J Chron Obstruct Pulmon Dis. 2017 Mar 22;12:981-987. doi: 10.2147/COPD.S128689. eCollection 2017. PMID: 28356730 Free PMC article. 
• Does urinary peptide content differ between COPD patients with and without inherited alpha-1 antitrypsin deficiency? Carleo A, Chorostowska-Wynimko J, Koeck T, Mischak H, Czajkowska-Malinowska M, Rozy A, Welte T, Janciauskiene S. Int J Chron Obstruct Pulmon Dis. 2017 Mar 8;12:829-837. doi: 10.2147/COPD.S125240. eCollection 2017. PMID: 28331304 Free PMC article. 
• Benefits of High-Intensity Exercise Training to Patients with Chronic Obstructive Pulmonary Disease: A Controlled Study. Boeselt T, Nell C, Lütteken L, Kehr K, Koepke J, Apelt S, Veith M, Beutel B, Spielmanns M, Greulich T, Vogelmeier CF, Kenn K, Janciauskiene S, Alter P, Koczulla AR. Respiration. 2017;93(5):301-310. doi: 10.1159/000464139. Epub 2017 Mar 23. PMID: 28329753 Clinical Trial. 
• Protean proteases: at the cutting edge of lung diseases. Taggart C, Mall MA, Lalmanach G, Cataldo D, Ludwig A, Janciauskiene S, Heath N, Meiners S, Overall CM, Schultz C, Turk B, Borensztajn KS. Eur Respir J. 2017 Feb 8;49(2):1501200. doi: 10.1183/13993003.01200-2015. Print 2017 Feb. PMID: 28179435 Review. 
• Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene. Matamala N, Aggarwal N, Iadarola P, Fumagalli M, Gomez-Mariano G, Lara B, Martinez MT, Cuesta I, Stolk J, Janciauskiene S, Martinez-Delgado B. PLoS One. 2017 Jan 20;12(1):e0170533. doi: 10.1371/journal.pone.0170533. eCollection 2017. PMID: 28107454 Free PMC article.
• The prevalence of diagnosed α1-antitrypsin deficiency and its comorbidities: results from a large population-based database.  Greulich T, Nell C, Hohmann D, Grebe M, Janciauskiene S, Koczulla AR, Vogelmeier CF. Eur Respir J. 2017 Jan 4;49(1):1600154. doi: 10.1183/13993003.00154-2016. Print 2017 Jan. PMID: 27824593 

2016

• Angiopoietin-like protein 4 and cardiovascular function in COPD. Waschki B, Kirsten AM, Holz O, Meyer T, Lichtinghagen R, Rabe KF, Magnussen H, Welte T, Watz H, Janciauskiene S. BMJ Open Respir Res. 2016 Oct 31;3(1):e000161. doi: 10.1136/bmjresp-2016-000161. eCollection 2016. PMID: 27933182 Free PMC article. 
• Advances in Identifying Urine/Serum Biomarkers in Alpha-1 Antitrypsin Deficiency for More Personalized Future Treatment Strategies. Ferrarotti I, Corsico AG, Stolk J, Ottaviani S, Fumagalli M, Janciauskiene S, Iadarola P. COPD. 2017 Feb;14(1):56-65. doi: 10.1080/15412555.2016.1241760. Epub 2016 Nov 9. PMID: 27827549 Review. 
• Different Training-Induced Skeletal Muscle Adaptations in COPD Patients with and without Alpha-1 Antitrypsin Deficiency.  Jarosch I, Gehlert S, Jacko D, Koczulla RA, Wencker M, Welte T, Bloch W, Janciauskiene S, Kenn K. Respiration. 2016;92(5):339-347. doi: 10.1159/000449509. Epub 2016 Sep 30. PMID: 27686000 
• Why do some adults with PiMZ α1-antitrypsin develop bronchiectasis? [corrected]. Aggarwal N, Delgado BM, Salipalli S, Matamala N, Rademacher J, Schwerk N, Welte T, Janciauskiene S, Ringshausen FC. ERJ Open Res. 2016 Jun 6;2(2):00021-2016. doi: 10.1183/23120541.00021-2016. eCollection 2016 Apr. PMID: 27730187 Free PMC article. 
• Well-Known and Less Well-Known Functions of Alpha-1 Antitrypsin. Its Role in Chronic Obstructive Pulmonary Disease and Other Disease Developments. Janciauskiene S, Welte T. Ann Am Thorac Soc. 2016 Aug;13 Suppl 4:S280-8. doi: 10.1513/AnnalsATS.201507-468KV. PMID: 27564662 Review.
• Neutrophilic panniculitis and autoinflammation: what's the link?: reply from authors. Blanco I, Lipsker D, Lara B, Janciauskiene S. Br J Dermatol. 2016 Sep;175(3):647-8. doi: 10.1111/bjd.14614. Epub 2016 Jul 27. PMID: 27463611 No abstract available.
• α-Linoleic acid enhances the capacity of α-1 antitrypsin to inhibit lipopolysaccharide induced IL-1β in human blood neutrophils. Aggarwal N, Korenbaum E, Mahadeva R, Immenschuh S, Grau V, Dinarello CA, Welte T, Janciauskiene S. Mol Med. 2016 Dec;22:680-693. doi: 10.2119/molmed.2016.00119. Epub 2016 Oct 4. PMID: 27452044 Free PMC article.
• Organizing pneumonia in mice and men. Izykowski N, Kuehnel M, Hussein K, Mitschke K, Gunn M, Janciauskiene S, Haverich A, Warnecke G, Laenger F, Maus U, Jonigk D. J Transl Med. 2016 Jun 10;14(1):169. doi: 10.1186/s12967-016-0933-6. PMID: 27282780 Free PMC article.
• The protease inhibitor cystatin C down-regulates the release of IL-β and TNF-α in lipopolysaccharide activated monocytes.Gren ST, Janciauskiene S, Sandeep S, Jonigk D, Kvist PH, Gerwien JG, Håkansson K, Grip O. J Leukoc Biol. 2016 Oct;100(4):811-822. doi: 10.1189/jlb.5A0415-174R. Epub 2016 May 17. PMID: 27190304
• Alpha-1 Antitrypsin Regulates Transcriptional Levels of Serine Proteases in Blood Mononuclear Cells. Aggarwal N, Koepke J, Matamala N, Martinez-Delgado B, Martinez MT, Golpon H, Stolk J, Janciauskiene S, Koczulla R. Am J Respir Crit Care Med. 2016 May 1;193(9):1065-7. doi: 10.1164/rccm.201510-2062LE. PMID: 27128707 No abstract available.
• Neutrophilic panniculitis associated with alpha-1-antitrypsin deficiency: an update. Blanco I, Lipsker D, Lara B, Janciauskiene S. Br J Dermatol. 2016 Apr;174(4):753-62. doi: 10.1111/bjd.14309. Epub 2016 Jan 27. PMID: 26595240 Review.
   

Abgeschlossene Doktorarbeiten / Completed Doctoral Thesis

• Dr. rer. nat Srinu Tumpara: Functional activities and Molecular forms of Alpha-1 antitrypsin, November 2022

Forschungspreise / Scientific Awards

• Kokilavani Sivaraman, M. Sc., Alpha1 Science Award 2023, CSL Behring (5.000 €) for the research work "Conformational plasticity of AAT: importance in a broadspectrum of inflammatory, tissue-repair, and immunomodulatory activities"
• Srinu Tumpara, M. Sc., Alpha1 Science Award 2022, CSL Behring (5.000 €) for the research work "Polymerization of misfolded Z alpha-1 antitrypsin protein lowers CX3CR1 expression in human PBMCs"
• Srinu Tumpara, M. Sc., ALTA Award 2018, Grifols, (50.000 €) for the project "Detection of short transcripts of SERPINA1 gene in patients with PiZZ and PiMM liver and lung diseases"

Posterpreis / Poster Award

• Kokilavani Sivaraman, Liu Bin, Julia Held, Sabine Wrenger, Thomas Iliig, Sonja Vollan2, Tobias Welte, Sabina Janciauskiene, Models of Lung Disease, 22th-23th June 2023, Fraunhofer ITEM Hannover, for the poster "Responses of human bronchial epithelial cells and microvascular lung endothelial to serum from SARS CoV-2 infected patients with different WHO Clinical Progression Scales (WHO-CPS)" 

Ambitionierte Medizinstudenten und Naturwissenschaftler (m/w/d) für wissenschaftliche Doktorarbeiten gesucht!

Wir, das ist die Forschungsgruppe Molekulare Pneumologie von Prof. Sabina Janciauskiene-Wallmark aus der Universitätsklinik für Pneumologie der MHH, arbeiten in unseren wissenschaftlichen Projekten und klinischen Studien an der Schnittstelle zwischen der Grundlagenforschung und der klinischen Forschung. Generell interessieren uns die Mechanismen, die bei akuten und chronischen Entzündungen involviert sind, vor allem die unterschiedlichen Rollen von Akute-Phase-Proteinen bei Lungen- und Lebererkrankungen und bei Krebs. Im Speziellen untersuchen wir native und post-translational modifizierte Formen von Alpha1-Antitrypsin (AAT), einem der wesentlichen humanen Proteaseinhibitoren, das gleichzeitig auch ein breites Spektrum an immun-modulatorischen Eigenschaften aufweist.

Für hoch motivierte, ambitionierte Studenten der Medizin oder Lebenswissenschaften, die wissenschaftliche Forschung auf höchstem Niveau durchführen möchten, bieten wir folgende Projekte ihre Doktorarbeit an:

1. Forscher haben ein großes Interesse an AAT, weil etwa 1-3% der Kaukasier einen schwere, erblichen AAT-Mangel haben, der ein Risiko für die Entwicklung einer frühen Form des Lungenemphysems darstellt und in jedem Alter Lebererkrankungen, wie Steatose, Fibrose, Zirrhose, und selbst Leberkrebs hervorrufen kann. In manchen Fällen mit dem schweren AAT-Mangel können Hauterkrankungen und entzündliche Darmerkrankungen auftreten. Deshalb wird aus humanem Plasma aufgereinigtes AAT zur Substitutionstherapie eingesetzt. Unser erstes Projekt beschäftigt sich mit der Untersuchung der Effekte der AAT-Therapie auf die Entstehung und das Fortschreiten von Erkrankungen der Lunge und der Leber.
2. Aktuell testen Pharmafirmen neuartige Herangehensweisen in Patientenkohorten, wie die Hemmung der Bildung des mutierten fehlgefalteten AAT-Proteins, das für den AAT-Mangel in der Zirkulation verantwortlich ist. In diesem Projekt sollen die Folgen der Eliminierung von AAT in vitro und in vivo adressiert werden.
3. Es gibt reichlich Evidenz dafür, dass AAT an der Entstehung, dem Wachstum und der Metastasierung von verschiedenen Krebstypen, inkl. Lungenkrebs beteiligt ist. Unsere Ergebnisse aus Untersuchungen an Lungenkrebszelllinien in vitro und Kohorten aus Patienten mit Lungenkrebs weisen darauf hin, dass AAT ein Modulator der Proliferation, Koloniebildung und Invasivität von Krebszellen und der Response auf Chemotherapien ist. Außerdem scheinen die Effekte von AAT von dessen molekularer Form, den Eigenschaften der Krebszellen, insbesondere dem Lipidmetabolismus und der Tumormikroumgebung abhängig zu sein. Dieses Projekt fokussiert auf die Mechanismen, die die Wirkung von AAT auf Krebszellen und Krebsgewebe in vitro und in biologischen Proben von Lungenkrebspatienten vermitteln.
4. Jüngste Befunde weisen darauf hin, dass AAT die Aufnahme des SARS-CoV-2 Coronavirus in die Zellen reguliert und höhere AAT-Plasmaspiegel einen positiven Effekt auf Patienten mit COVID-19 hat. Diese positive Wirkung von AAT wurde in einer kleinen Patientengruppe dokumentiert. In unserem vierten Projekt werden die biologischen Effekte von rekombinanten Spike-Proteinen auf humane Leukozyten, primäre humane bronchiale Epithelzellen und Endothelzellen der Lunge in vitro untersucht.

In unseren Projekten kommen modernste experimentelle Methoden für in vitro Untersuchungen und für die Untersuchung von ex vivo Patientenmaterial zur Anwendung.

Prof. Sabina Janciauskiene, PharmD, PhD (Arbeitsgruppenleiterin)
Tel: 0511 532 7297
Email: janciauskiene.sabina@mh-hannover.de

Projects for PhD and MD students (f/m/d)

We need support from highly motivated and ambitious life sciences and/or medical students to pursue scientific research at the highest level in the projects listed below.

Translational research projects, together with clinical studies, are the core of our group.  Our aim is to build a bridge between basic and clinical research. Our general interest is to study the mechanisms involved in acute and chronic inflammation, with particular focus on the diverse roles of acute-phase proteins in lung and liver diseases, and in cancer. More specifically we are interested in native and post-translationally modified forms of α1-antitrypsin (AAT), one of the major human protease inhibitors having broad immunomodulatory properties.

1. Researchers have a considerable interest in AAT because about 1-3% of Caucasians have severe inherited AAT deficiency, which is a high-risk factor for developing early onset emphysema and at any age liver diseases, such as steatosis, fibrosis, cirrhosis, and even hepatocellular carcinoma. In some cases, individuals with severe deficiency of AAT can also develop skin diseases and inflammatory bowel diseases. Therefore, purified human plasma AAT is used as an augmentation therapy. Our first project focuses on the effects of AAT therapy on lung and liver disease development and progression.  
2. Currently, companies in patient cohorts are testing novel approaches, one of which is to silence in the liver the production of the mutant misfolded AAT protein (causing the deficiency of AAT in the circulation). Our second project aims to investigate the consequences of AAT elimination in vitro and in vivo.
3. There is ample evidence for the involvement of AAT in the development, growth, and metastasis of various types of cancer, including lung cancer. Our results from lung cancer cell lines in vitro and findings from lung cancer patient cohorts suggest that AAT is a modulator of cancer cell proliferation, colony formation, invasiveness, and responses to chemotherapies. Moreover, the effects of AAT seem to depend on its molecular form, cancer cell properties, specifically lipid metabolism, and the microenvironment of cancer cells. Our third project focuses on the mechanisms involved in AAT effects on cancer cells and cancer tissues in vitro, and in biological samples from lung cancer patient cohorts.
4. Current findings provide evidence that AAT regulates the entry of the SARS-CoV-2 coronavirus into cells and that higher plasma levels of AAT have a positive effect in patients with COVID-19. The positive impact of AAT therapy was documented in small cohorts of COVID-19 patients. Our fourth project focuses on the biological effects of recombinant spike proteins on human blood cells, on human primary bronchial epithelial and lung endothelial cells in vitro.

Projects involve all modern methods for experiments in vitro and in patient materials ex vivo.

Prof. Sabina Janciauskiene, PharmD, PhD (Principal Investigator)
Phone: +49 511 532 7297
Email: janciauskiene.sabina@mh-hannover.de

Postdoc (f/m/d)

A postdoctoral research position at the Department of Respiratory Diseases, Hannover Medical School, is available to study usability of the acute phase protein alpha1-antitrypsin (AAT) to prevent serious COVID-19 course with an unfavorable outcome of SARS-COV2 corona virus infected patients. The project includes examinations of immune cells from healthy donors and patients with COVID-19 and analyses of their bronchial lavage and plasma samples by different methods including immune fluorescent cell analyses, functional assays, and analysis of gene and protein expression by PCR, Western Blot, ELISA techniques.
The project entitled
“Untersuchungen von Alpha1-Antitrypsin als Immunmodulator ex vivo in Patienten mit COVID-19-Infektion und Risiko eines schweren Verlaufs”
is part of the innovation network initiative „Die Rolle von Alpha-1-Antitrypsin als Immunmodulator zur Prävention eines schweren COVID-19 Verlaufs in Risikopatienten (COVAAT)“ supported by the European Regional Development Fund (ERDF).

Requirements:
Candidates should be highly motivated and focused, must hold a Ph.D., M.D./Ph.D. or Dr. rer. nat. degree in cell/molecular biology or related field, have one or more first author original research publication, the ability to hold deadlines, the willingness to train students and technicians, and good English language skills.

Qualifications:
Experience and expertise in mammalian cell culture (e.g., proliferation/ apoptosis/ migration / adherence/ phagocytosis), biochemical and molecular biology techniques (including qPCR), Western blotting, as well as basics in rodent models is required. Experience with isolation of PBMCs and neutrophils from human blood and experience with primary endothelial cell culture is highly desired. Experience with epithelial cell cultures at air-liquid-interface, immunohistochemistry is desired but not mandatory.

Hannover Medical School (MHH)
The MHH one of the leading university hospitals in Germany and a center for supramaximal care for patients with the most complex and severe diseases. We offer a team-oriented environment with a structured mentoring/professional development program. Our group has strong connections to Hannover Biomedical Research School, Pathology, Pediatric Pneumology, Gastroenterology and Hepatology, Transfusion Medicine and Hematology departments on the campus, and the Fraunhofer Institute (ITEM) in the neighborhood. Salary will be according to TV-L E13. Benefits are excellent. Hannover is located in the center of Germany and combines a broad cultural and recreational program with moderate costs of living.
Start date of the above position is on October 1, 2021. Applications will be considered for interview until the position is filled.

Disabled candidates with equivalent qualifications will receive preferential consideration. Hannover Medical School is an equal opportunity employer and encourages female/male/diverse scientists to apply. Please submit your application materials including CV, publication list, 1/2-page personal statement (interests/research experience) and two reference letters to:

Prof. Sabina Janciauskiene, PharmD, PhD (Principal Investigator)
Phone: +49 511 532 7297
Email: janciauskiene.sabina@mh-hannover.de
Website: www.mhh.de/pneumologie/forschung/mol-pneumo