member-academic-staff

Shulamit Levenberg

Shulamit Levenberg
Dean, Professor, Stanley and Sylvia Shirvan chair in cancer and life sciences
+972(4)8294810 /or/ +972(4)8295502
Silver 169 or Silver 303
  • CV

    Education:  

    • 1999: Ph.D., Direct Ph.D. program, Molecular Cell Biology Department,  Weizmann Institute of Science, Rehovot, Israel. Supervisor: Prof. Benjamin
    • Geiger.Thesis: The Structure and Function of Adhesion Signaling Complexes
    • 1992: B.Sc., Magna Cum Laude, Biology, Faculty of Life Sciences, Hebrew University,Jerusalem, Israel
    Academic appointments:  
    • Feb 2015-present:  Professor, Biomedical Engineering Department, Technion, Israel Institute of Technology
    • Sep 2011-July 2012: Visiting Professor, Wyss Institute for Biologically Inspired Engineering, Harvard University
    • May 2009- present:  Associate Professor, Biomedical Engineering Department, Technion, Israel Institute of Technology
    • Oct. 2004-  April 2009:  Senior Lecturer, Biomedical Engineering Department, Technion, Israel Institute of Technology
    • Summer 2006: Visiting Scientist, Prof. Robert Langer Lab, Chemical Engineering Department, MIT
    • Sept. 2002- July 2004:  Research Associate, Prof. Robert Langer Lab, Chemical Engineering Department, MIT.
    • Sept. 2001- Aug 2002:  Post Doctorate Associate, Prof. Robert Langer Lab, Chemical Engineering  Department, MIT.
    • Sept. 1999- Aug 2001:  Post Doctorate fellow, EMBO Fellowship, Prof. Robert Langer Lab, Chemical & Biomedical Engineering Department, MIT.
     

    Short Bio:

      Prof. Levenberg conducts interdisciplinary research on stem cells and tissue engineering. She did her PhD at the Weizmann institute on cell adhesion, and her post doctorate research on tissue engineering with Prof. Robert Langer at MIT. Her research showed that it is possible to create complex tissues including blood vessels in a laboratory and that these engineered tissue-constructs can integrate with the host when implanted. She is also developing micro bioreactors and nanoliter droplet devices for stem cell growth and manipulations. Levenberg received the Krill Prize for excellence in scientific research by the Wolf Foundation, and was named by Scientific American as a “Research Leader” in Tissue Engineering.

  • Selected Publications

    1. Shandalov Y, Egozi D, Freiman A, Dado-Rosenfeld D and Levenberg S. A method for constructing vascularized muscle flap. Methods. 84:70-5 (2015)
    2. Lesman A, Rosenfeld D, Landau S, Levenberg S, Mechanical regulation of vascular network formation in engineered matrices, Advanced Drug Delivery Reviews, 96:176-82 (2015)
    3. Ben-Arye T, Park S, Shemesh J, Peer D, Levenberg S, Yossifon G. Dielectrophoretic characterization of cells in a stationary nanoliter droplet array with generated chemical gradients. Biomed Microdevices.17(5):9996 (2015)
    4. Blinder Y, Raindel N, Mooney DJ and Levenberg S. Vasculogenic dynamics in 3D engineered tissue constructs. Nature Scientific Reports. 5:17840 (2015)
    5. Egozi D, Shandalov Y, Dado-Rosenfeld D, Freiman A, Ben-Shimol D., Levenberg S. Engineered vascularized muscle flap. J Vis Exp. Jan 11;(107) (2016).
    6. Freiman A, Shandalov Y, Rozenfeld D, Shor E, Segal S, Ben-David D, Meretzki S, Egozi D and Levenberg Adipose-derived endothelial and mesenchymal stem cells enhance vascular network formation on 3D constructs in vitro. Stem Cell Research & Therapy. 7:5 (2016)
    7. Dado-Rosenfeld D, Landau S, Shandalov Y, Raindel N, Shor E, Blinder Y, Vandenburgh H, Mooney D and Levenberg S. Morphogenesis of 3D vascular network is regulated by tensile forces. PNAS 113(12):3215-20
    8. (2016)
    9. Marom A., Shor E., Levenberg S. and Shoham S. Spontaneous activity characteristics of 3D “Optonets” Neurosci., 10:602. (2017)
    10. Landau S, Szklanny AA, Yeod GC, Shandalov Y, Kosobrodova E,. Weiss AS, Levenberg S. Tropoelastin coated PLLA-PLGA scaffolds promote vascular network formation. Biomaterials (2017), doi: 10.1016/j.biomaterials.2017.01.015.
    11. Perry L, Flugelman M, Levenberg S, Elderly Patient-Derived Endothelial Cells for Vascularization of Engineered Muscle. Molecular Therapy. 25(4):935-948 (2017)
    12. Freiman A, Shandalov Y, Rozenfeld D, Shor E., Ben-David D., Meretzki S., Levenberg S. and Egozi D. Engineering Vascularized Flaps Using Adipose-Derived Microvascular EC and MSC. Tissue engineering and regenerative medicine. doi: 10.1002/term.2436 (2017)
    13. Zohar B., Blinder B., Mooney DJ., Levenberg S. Flow-Induced Vascular Network Formation and Maturation in Three-Dimensional Engineered Tissue. ACS Biomaterials Science & Engineering. In Press (2017)
    14. Avesar , Rosenfeld R., Truman-Rosentsvit M., Ben Arye T., Geffen Y., Bercovici M., and Levenberg S. Rapid phenotypic antimicrobial susceptibility testing using nanoliter arrays. PNAS. 114(29):E5787-E5795. (2017)
    15. Ben-Shaul S., Landau S., and Levenberg S. Pre-ordered vessels halt ischaemia. Views and news. Nature Biomedical Engineering. DOI: 10.1038/s41551-017-0089 (2017)
    16. Ganz J*, Shor E*, Guo S, Sheinin A, Arie I, Michaelevski I, Pitaru S, Offen D, Levenberg S. Implantation of 3D constructs embedded with oral mucosa-derived cells induces functional recovery in rats with complete spinal cord transection. Neurosci. 11:589 (2017)
    17. Landau S. and Levenberg S. Localization of engineered vasculature within 3D tissue constructs. Bioengineering and Biotechnology. 6:2 (2018)
    18. Kaufman T*., Kaplan B*., Perry , Shandalov Y., Landau S., Srugo I., Ad-El D. and Levenberg S. Innervation of an engineered muscle graft for reconstruction of muscle defects. American Journal of Transplantation. 1–11 (2018)
    19. Avesar J., Blinder Y., Aktin H., Szklanny A., Rosenfeld D., Savir J., Bercovici and Levenberg S. Nanoliter cell culture array with tunable chemical gradients. Analytical Chemistry. 90 (12):7480–7488 (2018)
    20. Landau , Ben-Shaul S. and Levenberg S. Oscillatory strain promotes vessel stabilization and alignment through fibroblast YAP-mediated mechanosensitivity. Advanced Science. 1800506 (2018)
    21. Shor E., Merdler U., Brosh I., Shoham and Levenberg S. Neuro-vascular interactions in engineered neural implants modulate morphology and activity characteristics both in vitro and in vivo. Biomaterials (2018) In press
     

  • Main Research Interests

    Research interests: Vascularization of engineered tissues. Stem cell differntiation on 3D scaffolds.Controling stem cell microenvironments  

  • Research Topics

    Research

    The rapidly increasing demand for organ and tissue transplantation has promoted tissue engineering and stem cell research as promising approaches. Tissue engineering combines cells, growth factors and 3D scaffolds for repair and regeneration of biological tissues. To advance tissue engineering research, scaffold properties must be optimized for a given application and cell type. This includes chemical and mechanical properties, shape, and structure and degradation rate.  In addition co-culture approaches are required to allow organization of complex tissue structures. Endothelial cell co-cultures are important for inducing vascularization of engineered tissues. Our experiments in engineered skeletal and cardiac muscle tissue indicate that endothelial cells promoted differentiation and organization of the co-cultured myoblasts. Endothelial 3D tubular networkswere formed within the tissue and shown to promote vascularization upon implantation. Our recent results using pancreatic islets co-cultures further support the inductive effect of endothelial vessels on islets survival in vitro and in vivo. Given the attractive potential of human embryonic stem cells in tissue regeneration we evaluate the ability to differentiate the cells and induce their 3D organization toward formation of complex tissues.  Porous biodegradable polymer scaffolds are ideal system for exploring 3D tissue formation, providing support for the cells that can be modulated by modifying cell adhesion sites. Following degradation, the polymers can promote further growth of cells and provide space for remodeling of tissue structures. In addition, degradation of the scaffolds can be used as a tool for localized and controlled growth factor supplementation. Biodegradable, growth factor-eluting nano-fibers are also used to study embryonic stem cells process in 3D models. Differentiation of the cells is further studied in micro perfusion system to allow the precise localization of a growth factor,  both temporally and spatially using laminar flows. The technique can provide a tool to investigate cell-cell signaling between adjacent embryonic stem cells by maintaining a constant gradient of growth factors in the surrounding culture medium. Understanding stem cells differentiation and 3D cellular communications can lead to advances in cell therapy and tissue engineering and facilitate organ and tissue regeneration.

    Vascularization of engineered tissue constructs

    The uniqueness of this approach (developed by Levenberg et al and first published in Nature Biotechnology 2005) is to induce vessel network assembly within 3D tissue constructs in vitro by multicellular culturing of endothelial cells (ECs) and vascular mural cells with cells specific to the tissue of interest. Levenberg has shown that such in vitro prevascularization of engineered tissue can promote its survival and vascularization upon implantation. The ongoing projects in the lab focuses on characterizing the mechanisms of in vitro vascularization and vessel-network formation in multi-cellular tissue constructs by using defined biomaterials and mechanical stimulation designed to mimic in vivo settings. In addition, this study aims to elucidate the signaling effects and in vivo integration process of engineered vessel network with host vasculature. Several in vivo models are being used for real-time investigation of the vascularization and integration of engineered vascularized constructs. In addition, new strategies are being developed for fabrication of engineering vascularized flaps. Additional focus is placed on the effects of interstitial flow and tensile forces on the self-assembly of endothelial cells into vascular networks in vitro. The effects are being characterized and quantified using a combination of bioreactor setups, computational modeling, 3D image analysis and gene expression studies. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501.  

    Engineering vascularized cardiac tissue

    Our aim is to create in vitro pre-vascularized cardiac tissue using a multi-cellular seeding strategy. This strategy involves co-culturing 3 types of cells (i.e. cardiomyocytes, endothelial cells and fibroblasts) within a nano-patterned scaffold.Cardiac tissue engineering aims to create functional tissue constructs that can re-establish the structure and function of injured myocardium. The cellular organization of the heart consists primarily of cardiomyocytes, fibroblasts, vascular smooth muscle cells, and endothelial cells. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501. Flow-induced vascularization in engineered tissue One of today’s major challenges in engineering complex three-dimensional functional tissues is proper vascularization – cells need to be in close proximity (~100µm) to blood vessels in order to survive. The research focuses on the effects of interstitial flow on the self assembly of endothelial cells into vascular networks in vitro. Using a combination of perfusion-bioreactor design, computational fluid dynamics (CFD) modeling, fluorescence microscopy image analysis and gene expression analysis, we are working to characterize and quantify these effects. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501. Engineering skeletal muscle tissue- as graft and flaps for reconstruction of abdominal wall tissue This study offers novel reconstruction techniques in the form of an alternative biomaterial implantation (vascularized engineered skeletal muscle tissue), offering the possibility to repair a full-thickness defect of the abdominal wall without the need to transfer tissue (autologous muscle free flap) from another site and minimal postoperative scarification. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501. Engineering a vascular niche to support pancreatic islet survival and function and to improve islet transplantation efficacy The working hypothesis of this study is that non-nutritional, EC-generated signals may be paramount to in vitro culturing of islets for the purpose of boosting early graft infusion survival prospects. The study aims to reconstruct pancreatic tissue consisting of islets or beta cell progenitors enriched with a vascular milieu that both supports and promotes graft integration and function. Particular focus is being placed on understanding the inductive signals and characterizing the resulting 3D vascular networks and on evaluating its capacity to treat a Type 1 diabetes. This research has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281501.  

    spinal cord injury regeneration

    Spinal cord injury is devastating to both patients and their families.  Among the strategies being investigated to promote regeneration is the transplantation of stem cells. We aims to exploit the supportive properties of stem cells and other neuronal cells in combination with endothelial cells and a biodegradable scaffold, as a strategy to preserve spared neural tissue, and promote a more hospitable environment for vasculogenesis and neural regeneration.

    Cell mechanics in 3D constructs

    In this project we investigate the mechanical interplay between cells and scaffold within 3D engineered constructs. We examine the influence of cells seeded within scaffold via measurements of contractile forces and the influence of mechanical constraints of the scaffold on cell behavior mainly focusing on embryonic stem cells differentiation.   We combine different methods such as tissue engineering techniques, bioreactors (and new designs), gene analysis and finite elements modeling.   Droplet Based Microfluidics We have developed innovative methods to create and manipulate nanoliter volume droplets in microfluidic channels. We were able to achieve on demand generation of nanoliter droplets, purely hydrodynamic droplet sorting, and accurate droplet composition control. Our latest work brought stationary nanoliter droplet arrays on a substrate of choice for the culture and analysis of single adherent and non-adherent cells. We are currently using  these modules to answer biological questions by implementing single cell assays.  

    The Rina & Avner Schneur Type II Diabetes center

    The Rina & Avner Schneur Type II Diabetes center lead by Prof. Levenberg, brings together top researchers from the faculty of Biomedical engineering and the Faculty of Medicine at the Technion-Israel Institute of Technology to seek for a cure to type II diabetes. Type II Diabetes (DM2) is one of the most important public health challenges requiring a cure rather than preventive treatment. The current project (In collaboration with Prof Eddy Karnieli) focuses on the development of a new cure for this important disease in the form of transplantation of engineered tissue, which will provide a useful tool to reach better systemic glucose homeostasis in DM2.