Natalie Fekete

Postdoctoral Fellow

Research Statement

My main focus of scientific interest is understanding cell-cell interactions and cell population dynamics. Deciphering the way cells interact with both their immediate culture environment as well as with their neighbouring cells is something that fascinates me. Cell signalling events following extracellular stimulation and subsequent alterations in cell fate are highly complex in their multitude and connectivity. Which is precisely why I find them so attractive to investigate.

The characterization of cell-subpopulations and cell-material interactions were already a focus of my studies as a PhD student, in which I also tracked cell fate in vivo using live MR imaging and infrared tomography. During this time, I was also introduced to the field of cell therapy, in which research groups are trying to find ways to use human cells as a therapeutic product. This idea has become the central nexus around which I built the core of my research work. 

My main goal is to advance our understanding of cell behaviour and cell fate in the context of generating cell therapy products.

Having touched on the field of cell-material interactions, I then investigated the effect of defined surface topographies on cell biology using a high-throughput micro-chip system, the TopoChip, during my first postdoctoral research study. This work in the field of tissue engineering helped me understand the effect of surface topography and mechanical forces on cell fate. However, I still did not fully understand the molecular interactions at the interface of cells with their culture surfaces, which is an essential step in controlling and directing cell fate in vitro.

Cell-material and cell-surface interactions are now the main pillars of my current second postdoctoral research project. The objective is to characterize the effect of commercially relevant cell culture surfaces on monocyte fate for therapeutic purposes. This project combines my knowledge of cell biology using donor-derived cells in a defined in vitro culture environment with the analytical technologies available in the field of chemical engineering. 

In my future work, I want to employ high-content imaging and live cell tracking at the cell-cell and cell-material interface to advance translational research for cell therapy. In combining approaches and technologies used in immunology, cell biology, tissue engineering and surface science I aim to better understand the current limitations and possibilities of innovative cell products for their clinical application in cell therapy.

Research Experience

Work History
Nov 2014 - Present

Postdoctoral Fellow

Department of Chemical Engineering, McGill University, Canada

Project: Effects of fluoropolymer surface properties on monocyte cell fate

The objective of this project is to study the interactions between human monocytes and commercially relevant culture surfaces. To this end, the different culture surfaces are tested for their effect on monocyte cell fate and their therapeutic potential.

Jan 2013 - Oct 2014

Postdoctoral Researcher

Department of Tissue Regeneration, University of Twente, The Netherlands

Project: STROMA – EU 7th FP PEOPLE 2011 ITN – Marie Curie

Using a library of pre-selected surface patterns, the aim of this project was to identify and validate those defined surface topographies that significantly elicit B cell-specific lymph node stromal cell architecture and function.

Jan 2013 - Oct 2014

R&D Scientist

MATERIOMICS B.V.

The main focus of my work at Materiomics B.V. was to develop and optimize assays to investigate cell-surface and cell-material interactions using the proprietary TopoChip high-throughput screening platform. To this end, I cultured primary human platelets, macrophages, MSCs and rhesus macaque-derived hepatocytes, identified appropriate screening targets and performed screening assays.

Aug 2009 - Dec 2012

Ph.D. thesis work

Institute of Transfusion Medicine, University of Ulm, Germany

Project: REBORNE – EU 7th FP HEALTH-2009-1.4-2

To track cell distribution and map the fate of MSCs in vivo  I used nanoparticle-based real-time imaging. In collaboration with the Department of Macromolecular Chemistry we investigated the effect of materials and cell-surface interactions on MSC viability and proliferation.

 

Project: CASCADE – EU 7th FP HEALTH–2007–1.4-7

The aim of this EU-wide project was to establish GMP-compliant clinical-scale expansion of bone marrow-derived MSCs both in bioreactor as well as in static tissue culture systems. Further, platelet lysate was developed as a novel cell culture supplement for cell therapy. Its effect on cell fate was extensively characterized in early and late passage MSCs, regarding both their phenotype and in vitro  migratory capacities.

Feb 2008 - Oct 2008

M.Sc. thesis work

Department of Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics

The objective of the project was to investigate the intracellular shuttling of the protein tyrosine phosphatase SHP-1 from the cytoplasm to the nucleus following B cell receptor stimulation. A mass spectrometric analysis was performed to identify SHP-1 binding partners in the nucleus. This improved our understanding of novel SHP-1-based signaling pathways.

Education

Education
2012

Dr. rer. nat. (equiv. to Ph.D.)

Institute of Organic Chemistry University of Ulm, Germany

Thesis: "Mesenchymal stromal cells for cell therapy: Good Manufacturing Practice-compliant expansion systems and nanoparticle-based imaging"

2009

Dipl.-Biol. (equiv. to M.Sc. in Biology)

Albert-Ludwigs-University & Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

Thesis: “Function of the protein tyrosine phosphatase SHP-1 in the nucleus”

Peer-Reviewed Articles

  • Brassard JA, Fekete N, Garnier A, Hoesli CA: Hutchinson-Gilford progeria syndrome as a model for vascular aging. Biogerontology 2015; Sep 2 (Epub ahead of print) 
  • Schneider V, Zhang L, Rojewski M, Fekete N, Schrezenmeier H, Erle A, Bullinger L, Hoffmann S, Götz M, Döhner K, Ihme S, Döhner H, Buske C, Feuring-Buske M, Greiner J: Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia-associated antigens. Int J Cancer 2015; DOI:10.1002/ijc.29583
  • Fekete N, Erle A, Fürst D, Rojewski M, Langonné A, Sensebé L, Schrezenmeier H: Effect of high-dose irradiation on human bone marrow-derived MSCs. Tissue Eng Part C Methods 2015 Feb;21(2):112-22.
  • Fekete N, Rojewski MT, Lotfi R, Schrezenmeier H: Essential Components for Ex Vivo Proliferation of Mesenchymal Stromal Cells. Tissue Eng Part C Methods 2014,20(2): 129-139
  • Vernikouskaya I, Fekete N, Erle A, Bannwarth M, Landfester K, Rojewski M, Schmidtke-Schrezenmeier G, Schrezenmeier H, Rasche V. Iron-loaded PLLA (iPLLA) Nanoparticles as Highly Efficient Intracellular Markers for Visualization of Mesenchymal Stromal Cells by MRI. Mol Imag Contrast Media Mol. Imaging 2014;9 109-121
  • Rojewski M*, Fekete N*, Baila S, Nguyen K, Fürst D, Antwiler D, Dausend J, Kreja L, Ignatius A, Sensebé L, Schrezenmeier H: GMP-compliant isolation and expansion of bone marrow-derived MSC in the closed, automated device Quantum Cell Expansion system. Cell Transplant. 2013;22(11):1981-2000 *contributed equally
  • Fekete N*, Rojewski M*, Fürst D, Kreja, L, Ignatius A, Dausend J, Schrezenmeier H: GMP-compliant isolation and large-scale expansion of bone marrow-derived MSC. PLoS ONE 2012; 7(8): e43255 *contributed equally
  • Wiehe JM, Kaya Z, Homann J, Wöhrle J, Vogt K, Nguyen T, Rottbauer W, Torzewski J, Fekete N, Rojewski M, Schrezenmeier H, Moepps B, Zimmermann O: GMP-adapted overexpression of CXCR4 in human mesenchymal stem cells for cardiac repair. Int J Cardiology 2012 Sep 1;167(5):2073-81
  • Fekete N, Gadelorge M, Fürst D, Maurer C, Dausend J, Fleury-Cappellesso S, Mailänder V, Lotfi R, Ignatius A, Sensebé L, Bourin P, Schrezenmeier H, Rojewski M: Platelet lysate from whole blood derived pooled platelet concentrates and apheresis derived platelet concentrates for isolation and expansion of human bone marrow mesenchymal stromal cells: Production process, content and identification of active components. Cytotherapy 2012 May;14(5):540-54
  • Schmidtke-Schrezenmeier G, Urban M, Musyanovych A, Mailänder V, Rojewski M, Fekete N, Menard C, Deak E, Tarte K, Rasche V, Landfester K, Schrezenmeier H: Labelling of mesenchymal stromal cells with iron oxide-poly(L-lactide) nanoparticles for magnetic resonance imaging: uptake, persistence, effects on cellular function and magnetic resonance imaging properties. Cytotherapy 2011Sep;13(8):962-75

Oral Presentations

  • Fekete N (2014): TopoChip screening of designed surfaces to instruct cell fate. Society for Biomaterials 2014 Annual Meeting, Denver, CO, USA. April 16-19. Transactions of the 38th Annual Meeting 2014. Volume XXXVI, #192, ISSN# 1526-7547.
  • Fekete N, Erle A, Schmidtke-Schrezenmeier G, Fürst D, Rojewski M, Schrezenmeier H: Effect of high dose radiation on human bone marrow-derived MSC. 46th Annual Congress of the German Society for Transfusion Medicine and Immunohematology (DGTI), Münster, Germany. September 24-27. Transfus Med Hemother 2013; 40(suppl 1):1-90
  • Fekete N, Vernikouskaya I, Bannwarth M, Erle A, Espig S, Rojewski M, Schmidtke-Schrezenmeier G, Landester K, Rasche V, Schrezenmeier H (2012): Imaging of iron oxide-PLLA-particle-labelled MSCs in vivo. 45th Annual Congress of the German Society for Transfusion Medicine and Immunohematology (DGTI), Graz, Austria. September 11-14. Transfus Med Hemother 2012;39(suppl 1):1-66
  • Fekete N, Vernikouskaya I, Bannwarth M, Erle A, Espig S, Rojewski M, Schmidtke-Schrezenmeier G, Landester K, Rasche V, Schrezenmeier H (2012): Monitoring of iron oxide-PLLA-particle-labelled MSCs in vivo. Perspectives in Cell- and Gene-Based Medicines. A joint Conference of the 18th Annual Meeting of the German Society for Gene Therapy (DG-GT), Perspective Conference of the Stiftung Hämotherapie-Forschung on the Role of Haemotherapy and Transfusion Medicine and 1st Symposium of the LOEWE Center for Cell and Gene Therapy Frankfurt (CGT), Frankfurt (Main), Germany. March 15-17
  • Rojewski M, Fekete N, Fürst D, Bourin P, Lotfi R, Mailänder V, Schmidtke-Schrezenmeier G, Sensebé L, Antwiler D, Schrezenmeier H (2010): GMP-grade large-scale expansion of human mesenchymal stem/stromal cells (MSC) by different methods. 1st European Conference on Mesenchymal Stem Cells, Toulouse, France, November 18-20
  • Fekete N, Fürst D, Lotfi R, Wiesneth M, Rojewski M, Schrezenmeier H (2011): Identification of the active components within human platelet lysate enhancing proliferation of mesenchymal stromal cells (MSC). 44th Annual Congress of the German Society for Transfusion Medicine and Immunohematology (DGTI), Hannover, Germany. September 27-30. Transfus Med Hemother 2011;38(Suppl.1):1-72
  • Fekete N, Sensebé L, Langonné A, Fürst D, Rojewski M, Schrezenmeier H, Schmidtke-Schrezenmeier G (2011): Effect of radiation on human bone marrow-derived mesenchymal stromal cells (MSC). 44th Annual Congress of the German Society for Transfusion Medicine and Immunohematology (DGTI), Hannover, Germany. September 27-30. Transfus Med Hemother 2011;38(Suppl.1):1-72
  • Fekete N, Rojewski M, Lotfi R, Schrezenmeier H (2010): Expression and function of chemokine receptors on mesenchymal stromal cells in early passages of GMP-grade large-scale ex vivo expansion. XXX. International Congress of the International Society of Blood Transfusion (ISBT) in joint cooperation with the 43rd Congress of the DGTI, Berlin, Germany. June 26 - July 1. Vox Sang 2010;99(Suppl.1):43-44