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Bogdan Iorga

 

 

Kontakt / Contact

 

Ph.D. Bogdan Iorga

Tel: ++49 511-532-2753

E-mail: Iorga.Bogdan(at)mh-hannover.de

 

Aktuelles Forschungsgebiet / Current research topics

 

Myofibrils and myofibrillar micromechanics. The main function of cardiomyocytes (CMs) to generate force and shorten their length occurs when the subcellular myofibrils contract due to multiple interactions between myosin motors and actin filaments. Myofibrils consist in many sarcomeres arranged in series driving directly the contraction-relaxation events of CMs upon cyclical variation of the intracellular Ca2+ concentration. Therefore, isolated myofibrils represent an established contractile model used to understand sarcomeric protein-related processes that determine contractile function of CMs in the absence of Ca2+ handling systems and of upstream signaling. Myofibrils can be investigated using fast kinetic techniques because they are thin and in rapid diffusional equilibrium with their surrounding environment. We have established a micromechanical setup that uses an atomic force cantilever as a nN-sensitive force sensor. This setup allows rapid changes of the solutions to which myofibrils are exposed, and the force kinetic parameters of myofibrillar activation and relaxation at different Ca2+ concentrations can be analyzed with high time resolution.

 

In vitro-differentiated cardiomyocytes. Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold great potential for the treatment of cardiovascular diseases by cell transplantation or engineered cardiac tissue, for assessing efficiency and toxicity of pharmacological compounds, or to be used as cellular disease models in vitro. hPSC-CMs exhibit a series of immature features compared to ventricular CMs of an adult human heart. Therefore, characterization of hPSC-CMs at different hierarchically interrelated levels (molecular, subcellular, cellular and multicellular levels) and understanding how extracellular environment and intracellular factors may affect hPSC-CMs development, in pathologic and non-pathologic conditions, represents important research objectives to us. (link to “Forschungsbericht 2017”)

 

My research interests are related to:

- understanding and identification of physical factors that could accelerate the functional maturation of hPSC-CMs in vitro toward a ventricular-like phenotype;

- defining the maturation stage of hPSC-CMs at different hierarchically interrelated levels (molecular, subcellular, cellular and engineered tissue levels) with the purpose to further use hPSC-CMs as contractile model for different cardiomyopathies;

- understanding the functional primary consequences of missense mutations (e.g., cardiomyopathy-linked mutations) occurring in sarcomeric proteins (e.g., in myosin motor) using the hPSC-CMs model at different maturation stages in comparative studies with adult human myocardial samples.

 

 

Werdegang / Career

 

  • 2013: Junior Professor
  • 2004: Ph.D. in Life Science – European Doctorate
  • 1996: M.Sc – Master, Biophysics
  • 1995: B.Sc. – University, Physics
  • 1990: Abitur/Baccalaureate – Mathematics and Physics 

 

 

 

Berufserfahrung und Forschungsthemen / Work experience and Research Topics

 

 

  • 2013-2019: Junior-professor (W1 position) for “Muscle Physiology and Pathophysiology”, Institute of Molecular and Cell Physiology, Hannover Medical School Research topics: Force-related kinetic studies with subcellular myofibrils using human myocardial samples and human embryonic/induced pluripotent stem cell-derived cardiomyocytes.
  • 2011-2013: Post-Doctoral position, Institute of Molecular and Cell Physiology, Hannover Medical School Research topics and Developments: (1) Establishment of the Myofibrils Micromechanical Setup; (2) Force-related kinetic studies with subcellular myofibrils in physiological and pathophysiological conditions using human and animal skeletal muscle samples.
    Forschungsbericht 2011  
  • 2005-2011: Post-Doctoral position, Institute of Vegetative Physiology, University of Cologne Research topics and Developments: (1) Force-related kinetic studies with subcellular myofibrils in physiological and pathophysiological conditions using different animal models (e.g., mouse, guinea-pig, rabbit, zebra-fish); (2) Sarcomeric proteins and functional phenotype in pediatric patients with conotruncal congenital heart defects; (3) Establishment of the small-perturbational sinusoidal method applied to Ca2+-activated skeletal myofibrils.
  • 2005: Post-Doctoral collaborative work, Department of Biosciences, University of Kent at Canterbury Research topic: Studies of temperature-dependent kinetic behavior of the fast and slow molecular motors in solutions.
  • 2004-2005: University junior assistant, Department of Physics and Applied Mathematics, Faculty of Chemistry, University of Bucharest
  • 2001-2004: European Doctorate Program (2004, Ph.D.) – EU Research Training Network FP5 (HPRN-CT-2000-00091), University of Montpellier-II & INSERM, and Department of Biosciences, University of Kent at Canterbury Research topic: Mechano-chemical coupling in skeletal myofibrils.
  • 1998-2001: University junior assistant, Department of Physics and Applied Mathematics, Faculty of Chemistry, University of Bucharest Research topics: (1) Electrochemical solution structures, (2) Kinetics of protein folding-unfolding processes
  • 1999-2000: University teaching assistant in collaboration with Department of Mathematics and Physics of the University of the Agronomic Sciences and Veterinary Medicine, Bucharest
  • 1997-1998: Research junior assistant, Institute of Physical-Chemistry of the Romanian Academy, Bucharest Research topic: Studies of kinetic processes in flammable gases
  • 1996-1997: Military service, second-lieutenant in the Air Forces (present status: inactive)
  • 1995-1996: Master studies in Biophysics (1996, M.Sc.), Research Center of Molecular Biophysics, Faculty of Physics, University of Bucharest Research topic: Fluorescence quenching study of chlorophyll-a by beta-carotene in benzene
  • 1990-1995: University studies in Physics (1995, B.Sc.), Faculty of Physics, University of Bucharest Research topic: Spectrophotometrical study of chlorophyll-a species in methanol aqueous Solutions

 

 

Forschungprojekte / Research Projects 

 

  • 2014-2017: Participant in the project “Functional characterization of myofibrils from human embryonic and induced pluripotent stem cells of FHC-patients”, Institute of Molecular and Cell Physiology, Hannover Medical School (funding: DFG)
  • 2013-2014: Participant in the project “Funktionelle Auswirkungen von FHC-assoziierten Mutationen in der Myosin-Kopfdomäne. Biomechanische Untersuchungen an einzelnen Muskelfasern aus M. soleus-Biopsien von FHC-Patienten”, Institute of Molecular and Cell Physiology, Hannover Medical School (funding: DFG)
  • 2011: Participant in the project “Structure, Function and Regulation of the Myofibrillar Z-disc Interactome“, Institute of Vegetative Physiology, University of Cologne (funding: DFG)
  • 2007-2009: Project topic “Funktionelle und biochemische Untersuchungen an isolierten Kardiomyofibrillen aus dem rechtsventrikulären Myokard von Patienten mit Fallot´scher Tetralogie”, project director: Iorga B., Institute of Vegetative Physiology, University of Cologne (funding: Köln-Fortune)
  • 2008: Project topic “Characterization of the consequences of cardiomyopathy-related mutations in troponin on the Ca2+-regulated cross-bridge kinetics – Enhanced Video Acquisition method”, project director: Iorga B., Institute of Vegetative Physiology, University of Cologne (funding: Maria-Pesch Stiftung)
  • 2007: Project topic “Characterization of the consequences of cardiomyopathy-related mutations in troponin on the Ca2+-regulated cross-bridge kinetics studies by sinusoidal force analysis on cardiac myofibrils (sinusoidal analysis method)”, project director: Iorga B., Institute of Vegetative Physiology, University of Cologne (funding: Imhoff-Stiftung)
  • 2005-2011: Participant in the project “Analyse sarkomerischer Dysfunktionen bei hypertropher und dilatativer Kardiomyopathie verursacht durch Mutationen des Troponin-Komplexes“, Institute of Vegetative Physiology, University of Cologne (funding: DFG)

 

 

Publikationen / Publications

  

Original Research:

  • Iorga B., Schwanke K., Weber N., Wendland M., Greten S., Piep B., dos Remeidos C.G., Martin U., Zweigerdt R., Kraft T., Brenner B. (2018) “Differences in Contractile Function of Myofibrils within Human Embryonic Stem Cell-Derived Cardiomyocytes vs. Adult Ventricular Myofibrils Are Related to Distinct Sarcomeric Protein Isoforms“, Frontiers in Physiology, 8:1111 DOI:10.3389/fphys.2017.01111 https://www.ncbi.nlm.nih.gov/pubmed/29403388  
  • Weber N., Greten S., Wendland M., Schwanke K., Iorga B., Fischer M., Geers-Knörr C., Hegermann J., Wrede C., Fiedler J., Kempf H., Franke A., Piep B., Pfanne A., Thum T., Martin U., Brenner B., Zweigerdt R., Kraft T. (2016) “Stiff matrix induces switch to pure β-cardiac myosin heavy chain expression in human ESC-derived cardiomyocytes”, Basic Research in Cardiology, 111:68 DOI: 10.1007/s00395-016-0587-9 https://www.ncbi.nlm.nih.gov/pubmed/27743117  
  • Elhamine F., Iorga B., Krüger M., Hunger M., Eckhardt J., Sreeram N., Bennink G., Brockmeier K., Stehle R., Pfitzer G. (2016) “The postnatal development of right ventricular myofibrillar biomechanics in relation to the sarcomeric protein phenotype in pediatric patients with conotruncal heart defects”, Journal of the American Heart Association, 5:e003699 DOI:10.1161/JAHA.116.003699 https://www.ncbi.nlm.nih.gov/pubmed/27353610  
  • Iorga B., Wang L., Stehle R., Pfitzer G., Kawai M. (2012) “ATP binding and cross-bridge detachment steps during full Ca²⁺ activation: comparison of myofibril and muscle fibre mechanics by sinusoidal analysis“, J Physiol.-London, 590: 3361-73 https://www.ncbi.nlm.nih.gov/pubmed/22586213
  • Lopez-Davila A.J., Elhamine F., Ruess D.F., Papadopoulos S., Iorga B., Kulozik F.P., Zittrich S., Solzin J., Pfitzer G., Stehle R. (2012) “Kinetic Mechanism of Ca(2+)-controlled changes of skeletal troponin I in psoas myofibrils”, Biophys. J, 103: 1254-64 https://www.ncbi.nlm.nih.gov/pubmed/22995498
  • Iorga B., Neacsu C.D., Neiss W.F., Wagener R., Paulsson M., Stehle R., Pfitzer G. (2011) “Micromechanical function of myofibrils isolated from skeletal and cardiac muscles of the zebrafish”, The Journal of General Physiology (ISSN: 0022-1295), Vol.137(3):255-270 http://www.ncbi.nlm.nih.gov/pubmed/21357732
  • Iorga B., Blaudeck N., Solzin J., Neulen A., Stehle I., Lopez-Davila A. J., Pfitzer G., Stehle R. (2008) “Lys184 deletion in troponin I impairs relaxation kinetics and induces hypercontractility in murine cardiac myofibrils”, Cardiovacular Research (ISSN: 0008-6363), Vol. 77:676-686 https://www.ncbi.nlm.nih.gov/pubmed/18096573
  • Roels B., Reggiani C., Reboul C., LionneC., Iorga B., Obert P., Tanguy S., Gibault A., Jougla A., Travers F., Millet G., Candau R. (2008) “Paradoxial effects of endurance training and chronic hypoxia on soleus myofibrillar ATPase activity”, American Journal of Physiology – Regulatory, Integrative and Comparative Physiology (ISSN: 0363-6119), Vol. 294(6):R1911-1918 https://www.ncbi.nlm.nih.gov/pubmed/18417650
  • Solzin J., Iorga B., Sierakowski E., Gomez-Alcazar D. P., Ruess D. F., Kubacki T., Zittrich S., Blaudeck N., Pfitzer G., Stehle R. (2007) “Kinetic mechanism of the Ca2+-dependent switch-on and -off of cardiac troponin in myofibrils”, Biophysical Journal (ISSN: 0006-3495), Vol. 93(11):3917-3931 http://www.ncbi.nlm.nih.gov/pubmed/17704185?dopt=Citation
  • Stehle R., Solzin J., Iorga B., Gomez D., Blaudeck N., Pfitzer G. (2006) “Mechanical properties of sarcomeres during cardiac myofibrillar relaxation: stretch-induced cross-bridge detachment contributes to early diastolic filling“, J. Muscle Res. Cell Motil. (ISSN: 0142-4319), Vol. 27:423-434 http://www.ncbi.nlm.nih.gov/pubmed/16897577?dopt=Citation
  • Iorga B., Candau R., Travers F., Barman T., Lionne C. (2004) “Does phosphate release limit the ATPase of relaxed soleus myofibrils? Evidence that (A)M×ADP×Pi states predominate on the cross-bridge cycle”, J. Muscle Res. Cell Motil. (ISSN: 0142-4319), Vol. 25 (4-5):367-378 http://www.ncbi.nlm.nih.gov/pubmed/15548866?dopt=Citation
  • Lionne C., Iorga B., Candau R., Piroddi N., Webb M. R., Belus A., Travers F., Barman T. (2002) "Evidence that phosphate release is the rate limiting step on the ATPase of psoas myofibrils prevented from shortening by chemical cross-linking", Biochemistry (ISSN: 0006-2960), Vol. 41:13297-13308 http://www.ncbi.nlm.nih.gov/pubmed/12403632?dopt=Citation
  • Semenescu G., Cioaca C., Iorga B. and Gughea G., (2002) "Phenonenological considerations rely on the double mixed electric layer model at the electrode-electrolyte interface", Acta Chimica Slovenica (ISSN: 1318-0207), 49:743-754 http://acta.chem-soc.si/49/49-4-743.pdf
  • Gazdaru D. M. and Iorga B., (2002) “Spectrophotometric analysis of the mixtures of photosynthetic pigments", Journal of Optoelectronics and Advanced Materials (ISSN: 1454-4164), vol.4, no.1:121-129 http://inoe.inoe.ro/JOAM/pdf4_1/Gazdaru.pdf
  • Semenescu G., Cioaca C., Iorga B. and Gughea G., (2002) "Mediator role of some organic substances in the charge transfer on metal-electrolyte interface", Acta Chimica Slovenica (ISSN: 1318-0207), 49:121-138 http://acta.chem-soc.si/49/49-1-121.pdf
  • Semenescu G., Cioaca C. and Iorga B., (2000) "A new phenomenological model describing conduction in electrolyte solutions", Acta Chimica Slovenica (ISSN: 1318-0207), 47:133-141 http://acta.chem-soc.si/47/47-2-133.pdf

 

Reviews and Editorials:

 

  • Stehle R., Iorga B. (2010) “Kinetics of cardiac sarcomeric processes and rate-limiting steps in contraction and relaxation“, J Mol Cell Cardiol (ISSN: 0022-2828), Vol.48(5):843-850 http://www.ncbi.nlm.nih.gov/pubmed/20060002
  • Stehle R., Solzin J., Iorga B., Poggesi C. (2009) “Insights into the kinetics of Ca2+-regulated contraction and relaxation from myofibril studies”, Pfluger Archives – European Journal of Physiology (ISSN: 0031-6768), Vol.458(2):337-57 https://www.ncbi.nlm.nih.gov/pubmed/19165498
  • Stehle R., Iorga B., Pfitzer G. (2007) “Calcium regulation of troponin and its role in the dynamics of contraction and relaxation”, American Journal of Physiology – Regulatory, Integrative and Comparative Physiology (ISSN: 0363-6119), Vol. 292(3):R1125-R1128 http://www.ncbi.nlm.nih.gov/pubmed/17158261

 

Text-Books and Lab-Books:

 

  • Iorga G., V. Iorga B. and Paun V. (2005) “Thermodynamics and Molecular Physics – Experimental workbook”, University Press, Bucharest, ISBN:973-737-116-X (chapters contribution)  
  • Danciulescu C., Iorga B. and Gughea G. (2000) “Physics. Electromagnetism”, University Press, Bucharest, ISBN:973-575-470-3 (chapter contribution)

  

  • Cioaca C. and Iorga B. (2000) “Fundamentals of electromagnetism and optics”, University Press, Bucharest, ISBN:973-575-428-2 (textbook)

  

  • Plosceanu C., Iorga B. and Gughea G. (1999) “Optics”, University Press, Bucharest, ISBN:973-575-305-7 (chapters contribution)