General Research InterestMy interests are focused on definition, detection and translational applications of circulating stem/progenitor cells. Because some of their properties and methods of characterization are shared with tumor cells, my lab is also currently developing projects in basic cancer biology.
Research Descriptiona) Detection of circulating endothelial and other progenitor cells in human blood, using an original solid phase assay (called CellTrap, in development). This project is funded through an ARRA/RC2/GO stimulus grant from NIH.
b) Study of plasticity of circulating progenitor cells towards the endothelial phenotype. Within another NIH funded project, we developed a novel model of neovascularization in adult animals, based on matrix degradation by migrating cells (‘tunneling’), followed by ‘cell columns’ formation and in situ differentiation of progenitor cells into ‘fibro-vascular bundles’.
c) Identification of biochemical factors limiting survival of circulating progenitor cells spontaneously recruited in damaged tissues. We are using mouse models of myocardial infarction, and transgenic animals deficient in the transcription factor slug involved in epithelial-to-mesenchymal transition. The project was funded by an American Heart Association Grant in Aid.
d) Biomechanical factors limiting the efficiency of cell therapy and in general the traffic of cells (including tumor cells) in the bloodstream. In this regard, we defined and now we are studying experimentally the cellular structural robustness, and developing new computational models of cell structure. We are also exploring the role of water in the control of biomechanical properties of the cytoskeleton. A subproject is being funded by an Pelotonia Undergraduate Award.
e) Use of progenitor cells for tissue engineering of peri-implant space. This project, also funded by NIH and a seed grant from Institute of Materials Research at OSU proposes a different approach to deal with the ubiquitous ‘foreign body’ reaction and subsequent fibrous encapsulation affecting implanted biosensors and drug delivery devices: namely to ‘treat’ them before impanation with stem/progenitor cells for stimulation peri-implant neovascularization. As model implant we are using an oxygen sensor detectable by electronic paramagnetic resonance in live animals, materials obtained by electrospinning as scaffolds to harbor the cells, and mathematical modeling of neovascularization and to account for molecular diffusion around the implant. All these methods are either inspired from or applicable to cancer biology.
Transinstitutional WorkA. Collaborators at Ohio State University: Stuart L. Cooper, Jeff Chalmers and Michael Paulaitis (Identification of circulating progenitor cells by the CellTrap and other methods); Periannan Kuppusamy (Development of the implanted oxygen sensor detectable by EPR oximetry); Pravin Kaumaya (Application of peptide ligands to cell capture and targeted inhibition of neovascularization); John Lannutti and Jianjun Guan (Use of electrospun scaffolds for tissue engineering of peri-implant space). Keith Gooch (Optimization of cell seeding for induced neovascularization and other tissue engineering applications); William Malarkey (Impact of inflammation on circulating progenitor cells); Harsh Jain (Modeling oxygen diffusion in peri-implant space and after manipulation by stem cells administration); Raghu Machiraju (Multi-parametric image analysis); Nicoleta Roman (Cellular automata modeling of hydrophobic effect).
B. Collaborators within USA: Maria Grant, University of Florida at Gainesville (Role of circulating progenitor cells in retinal damage and repair); Daniel Irimia, Harvard Medical School, Microfluidic models of microcirculation). Jeffrey Fredberg, and Guillume Lenormand, Harvard University (Role of water in cellular biomechanics).
C. International Collaborators: Helen Byrne, University of Nottingham, UK (Mathematical models of neovascularization); Mihaela Crisan, University of Rotterdam, Netherlands (Progenitor cells for tissue engineering).