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Molecular Mechanisms of Pulmonary Vascular Diseases

Principal Investigator:

Dr. Soni Savai Pullamsetti PhD; F.Z.S.I.

 

Department IV, Max Planck Institute for Heart and Lung Research 

Associate Professor, Justus Liebig University, Giessen

Dr. Soni Savai Pullamsetti is a principle investigator at the Max Planck Institute for Heart and Lung Research, Bad Nauheim, and an associate professor at the Department of Internal Medicine, Justus Liebig University Giessen, Germany. Dr. Pullamsetti received her undergraduate degree from Osmania University, and Master of Science in Biotechnology from Central University, India. After finishing her PhD and postdoctoral work at Justus Liebig University, from 2011, she is appointed as a Principal Investigator in the Department of Lung Development and Remodeling at the Max Planck Institute for Heart and Lung Research in Bad Nauheim.

Dr. Pullamsetti serves as a co-area leader in the “Excellence Cluster for Cardio Pulmonary System (ECCPS II)”, a program committee member of the American Thoracic Society (ATS), and as a project leader and member of German Lung Center (DZL), and collaborative research center on lung diseases (UGMLC). Dr. Pullamsetti published in well-renowned scientific journals such as Nature Medicine, Science Translational Medicine, Journal of Clinical Investigation, American Journal of Respiratory and Critical Care Medicine, Circulation, International Journal of Cardiology and Molecular Biology of the Cell (Publications list Pullamsetti). She serves as a reviewer for well-renowned scientific journals. Currently she is serving at the editorial board of Scientific Reports and Pulmonary Vascular Research Institute (PVRI).

Scientific Focus

Dr. Pullamsetti´s has long standing interest in understanding the molecular mechanisms underlying Pulmonary Hypertension and Pulmonary Fibrosis with the goal of developing novel therapeutic strategies. 

Understanding the molecular mechanisms underlying pulmonary hypertension

Pulmonary hypertension is a progressive disease of multifactorial etiology, which has a poor prognosis and results in right heart failure. Based on histopathological appearance and treatment modalities, five subclasses of chronic pulmonary hypertension have been defined. However, to date, current therapies provide symptomatic relief and improves prognosis, but falls short of re-establishing structural and functional lung vascular integrity, and thus, handicap-free long-term survival. 

Dr. Pullamsetti´s group contributed to the discovery of tyrosine kinases and phosphodiesterases involvement in the neoplastic nature of the remodeled pulmonary vasculature of Pulmonary Hypertension and parenchymal remodeling underlying Pulmonary Fibrosis. She has studied these signaling pathways in great detail and explored their therapeutic potential for PH treatment successfully and forwarding therapeutic concepts from “Bench to Bedside”. 

 

Recently, Dr. Pullamsetti´s group research has focused to delineate the role of central downstream molecules, with a major focus on transcription factors (FoxO, Beta-catenin, HIF) and epigenetic mechanisms to different forms of Pulmonary Hypertension and to develop novel therapeutic strategies to reverse this devastating disease.

 

Specific projects:

  • Forkhead box O (FoxO) transcription factors role in the pathogenesis of Pulmonary Hypertension and Right Ventricular Remodeling
  • Beta-Catenin role in the pathogenesis of Pulmonary Hypertension and Right Ventricular Remodeling
  • Hippo signaling family: Role and regulation in Pulmonary Hypertension
  • Genome-wide mapping of epigenetic landscape in human Pulmonary Hypertension
  • Role and regulation of class I and IIa HDACs in Pulmonary Hypertension
  • Role of Jumonji domain containing proteins in Pulmonary Hypertension
  • Histological and molecular characterization of distal vascular remodeling in Chronic Thromboembolic Pulmonary Hypertension

Understanding the molecular mechanisms underlying Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) belongs to the family of idiopathic interstitial pneumonias (IIPs), representing the most aggressive form of a diffuse parenchymal lung disease and affecting up to 500.000 patients in the western world. With the exception of Pirfenidone and Nintedanib, there are currently no approved therapies for IPF, and IPF is still a disease with significant morbidity and mortality. Unraveling the molecular basis behind the remodeling events in the lung parenchyma, resulting in the loss of gas exchange units and the deposition of scar tissue in lung fibrosis, is desirable. 

 

Specific projects:

  • Forkhead box O (FoxO) transcription factors role in the pathogenesis of Pulmonary Fibrosis
  • Role and regulation of class IIa HDACs in Pulmonary Fibrosis

Publications

Search Pubmed

 

Top 10 Publications (out of 58) of Pullamsetti

1. Savai R, Al-Tamari HM, Sedding D, Kojonazarov B, Muecke C, Teske R, Capecchi MR, Weissmann N, Grimminger F, Seeger W, Schermuly RT, Pullamsetti SS. Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension. Nat Med. 2014; 20:1289-300.

 

2. Pullamsetti SS, Schermuly R, Ghofrani A, Weissmann N, Grimminger F, Seeger W. Novel and emerging therapies for pulmonary hypertension. Am J Respir Crit Care Med. 2014; 189:394-400.

 

3. Savai R, Pullamsetti SS, Kolbe J, Bieniek E, Voswinckel R, Fink L, Scheed A, Ritter C, Dahal BK, Vater A, Klussmann S, Ghofrani HA, Weissmann N, Klepetko W, Banat GA, Seeger W, Grimminger F, Schermuly RT. Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension. Am J  Respir Crit Care Med. 2012; 186:897-908.

 

4. Pullamsetti SS, Banat GA, Schmall A, Szibor M, Pomagruk D, Hänze J, Kolosionek E, Wilhelm J, Braun T, Grimminger F, Seeger W, Schermuly RT, Savai R. Phosphodiesterase-4 promotes proliferation and angiogenesis of lung cancer by crosstalk with HIF. Oncogene. 2013; 32:1121-34.

 

5. Pullamsetti SS, Doebele C, Fischer A, Savai R, Kojonazarov B, Dahal BK, Ghofrani HA, Weissmann N, Grimminger F, Bonauer A, Seeger W, Zeiher AM, Dimmeler S, Schermuly RT. Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension. Am J Respir Crit Care Med. 2012; 185:409-19.

 

6. Pullamsetti SS, Savai R, Dumitrascu R, Dahal BK, Wilhelm J, Konigshoff M, Zakrzewicz D, Ghofrani HA, Weissmann N, Eickelberg O, Guenther A, Leiper J, Seeger W, Grimminger F, Schermuly RT. The role of dimethylarginine dimethylaminohydrolase in idiopathic pulmonary fibrosis. Sci Transl Med. 2011; 3:87ra53.

 

7. Pullamsetti SS, Savai R, Schaefer MB, Wilhelm J, Ghofrani HA, Weissmann N, Schudt C, Fleming I, Mayer K, Leiper J, Seeger W, Grimminger F, Schermuly RT. cAMP phosphodiesterase inhibitors increases nitric oxide production by modulating dimethylarginine dimethylaminohydrolases. Circulation. 2011; 123:1194-204.

 

8. Kolosionek E, Savai R, Ghofrani HA, Weissmann N, Guenther A, Grimminger F, Seeger W, Banat GA, Schermuly RT, Pullamsetti SS. Expression and activity of phosphodiesterase isoforms during epithelial mesenchymal transition: the role of  phosphodiesterase 4. Mol Biol Cell. 2009; 20:4751-65.

 

9. Schermuly RT*, Pullamsetti SS*, Kwapiszewska G, Dumitrascu R, Tian X, Weissmann N, Ghofrani HA, Kaulen C, Dunkern T, Schudt C, Voswinckel R, Zhou J, Samidurai A, Klepetko W, Paddenberg R, Kummer W, Seeger W, Grimminger F. Phosphodiesterase 1 upregulation in pulmonary arterial hypertension: target for reverse-remodeling therapy. Circulation. 2007; 115:2331-9. (*Denotes equal contribution)

 

10. Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 2005; 115:2811-21.

Group Members

Post Docs:

Dr. Swati Dabral

 

Doktoral Students:

Prakash Chelladurai

Christian Mücke

Elisabetta Gamen

Pouya Sarvari

Dijana Iloska

Chanil Valasarajan

 

Technical Assistants:

Uta Eule

Natascha Wilker

Stephanie Lindner

 

Alumni:

Hamza Al-Tamari

Mario Schmoranzer

Sabrina Zydek

Nina Bender

Contact

Dr. Soni Savai Pullamsetti

Max Planck Institute for Heart and Lung Research

Parkstraße 1

61231 Bad Nauheim

Tel.: +49 (0) 6032 705-380

Fax: +49 (0) 6032 705-385

 

Assistant 

Monika Haselbauer

Tel.: +49 (0) 6032 705-249

Fax: +49 (0) 6032 705-471

© 2017 Max-Planck-Institut für Herz- und Lungenforschung, Bad Nauheim