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:
    • 1999-2002: Post Doctorate in Tissue engineering, MIT, Cambridge, USA. Supervisor: Prof. Robert Langer
    • 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:
    • Summer 2019 Visiting Professor, Medicine by Design, University of Toronto
    • Summer 2017 Visiting Professor, University of Western Australia.
    • 2017- present Dean, Biomedical Engineering Department, Technion, Israel Institute of Technology
    • 2016- present Stanley and Sylvia Shirvan Chair in cancer research and life science
    • 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
    • 2004-  April 2009:  Senior Lecturer, Biomedical Engineering Department, Technion, Israel Institute of Technology
    • Summer 2006: Visiting Scientist,  Robert Langer Lab, Chemical Engineering Department, MIT
    • 2002- July 2004:  Research Associate, Prof. Robert Langer Lab, Chemical Engineering Department, MIT.
    • 2001- Aug 2002:  Post Doctorate Associate, Prof. Robert Langer Lab, Chemical Engineering  Department, MIT.
    • 1999- Aug 2001:  Post Doctorate fellow, EMBO Fellowship, Prof. Robert Langer Lab, Chemical & Biomedical Engineering Department, MIT.

    Short Bio:
    Professor Shulamit Levenberg is the elected Dean of the Biomedical Engineering Department at the Technion. She also serves as the director of the Technion Center for 3D Bioprinting and The Rina & Avner Schneur Center for Diabetes Research. Prof Levenberg earned her PhD at the Weizmann Institute of Science, where she focused on cell adhesion dynamics and signaling, and pursued her post-doctoral research in tissue engineering at MIT, in the lab of Professor Robert Langer. In 2004, she joined the Technion Faculty of Biomedical Engineering where she conducts interdisciplinary research on stem cells and tissue engineering. 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. Prof Levenberg spent a sabbatical year (2011-2012) as a visiting professor at the Wyss Institute for Biology Inspired Engineering at Harvard University and a summer sabbatical (2017) at the University of Western Australia as a winner of the Raine Visiting Professor Award.  Prof Levenberg received the Krill Prize for excellence in scientific research, awarded by the Wolf Foundation, and was named by Scientific American as a “Research Leader” in tissue engineering, for her seminal work on vascularization of engineered tissues. She also received the France-Israel Foundation Prize, the Italian Excellence for Israel Prize, the Teva Research Prize and the Juludan Prize. In 2018, she received the Rappaport Prize for Biomedical Sciences and in 2019 received the Bruno prize.  Levenberg has authored over 100 publications, and presented her work in over 100 international conferences as an invited or keynote speaker. She is founder and CSO of two start-up companies in the areas of cultured meat and nanoliter arrays for rapid antimicrobial susceptibility testing.  She is a member of the Israel National Counsel for Bioethics and is actively involved in training young scientists.  
     

  • Selected Publications

      2019:


    • Ben-Shaul, S., Landau S., Merdler U. and Levenberg S. Mature vessel networks within engineered tissue promote graft-host anastomosis and prevent graft thrombosis. PNAS 116(8):2955-2960. doi: 10.1073/pnas.1814238116. Epub Feb 4 (2019)
    • Zohar, B., Blinder, Y., Epshtein, M., Szklanny, AA., Kaplan, B., Korin, N., Mooney DJ. and Levenberg S. Multi-flow channel bioreactor for monitoring cellular dynamics in a 3D engineered tissue. Communications Biology. 2:158. doi: 10.1038/s42003-019-0400-z (2019)
    • Ben-Arye, T. and Levenberg, S. Tissue Engineering for Clean Meat Production. Front. Sustain. Food Syst. 3: 89 (2019).
    • Szklanny, A. A., Debbi, L., Merdler, U., Neale, D., Muñiz, A., Kaplan, B., Guo, S., Lahann, J., Levenberg, S. High‐Throughput Scaffold System for Studying the Effect of Local Geometry and Topology on the Development and Orientation of Sprouting Blood Vessels. Advanced Functional Materials, 1901335. https://doi.org/10.1002/adfm.201901335 (2019)
    • Guo, S., Perets, N., Betzer,O., Ben-Shaul, S., Sheinin,A., Michaelevski,I., Popovtzer,R., Offen,D.,and Levenberg, S. Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog siRNA Repairs Complete Spinal Cord Injury, ACS Nano. 13 10015–10028. doi:10.1021/acsnano.9b01892. (2019)
    • Luba Perry, Uri Merdler, Maria Elishaev, and Shulamit Levenberg Enhanced Host Neovascularization of Prevascularized Engineered Muscle Following Transplantation into Immunocompetent versus Immunocompromised Mice, Cells, 8, 1472; doi:10.3390/cells8121472 (2019)

    2018:
    • Landau S. and Levenberg S. Localization of engineered vasculature within 3D tissue constructs. Front.  Bioengineering and Biotechnology. 6:2 (2018)
    • Kaufman T*., Kaplan B*., Perry L., 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. 19:(1) 37-47 (2018)
    • Avesar J., Blinder Y., Aktin H., Szklanny A., Rosenfeld D., Savir J., Bercovici M. and Levenberg S. Nanoliter cell culture array with tunable chemical gradients. Analytical Chemistry. 90(12):7480-7488. doi: 10.1021/acs.analchem.8b01017. Epub May 30 (2018)
    • Landau S., Ben-Shaul S. and Levenberg S. Oscillatory strain promotes vessel stabilization and alignment through fibroblast YAP-mediated mechanosensitivity. Advanced Science. 5(9):1800506 (2018)
    • Shor E., Merdler U., Brosh I., Shoham S. and Levenberg S. Neuro-vascular interactions in engineered neural implants modulate morphology and activity characteristics both in vitro and in vivo. Biomaterials. 80:1-11. doi: 10.1016/j.biomaterials.2018.07.001. Epub  Jul 4. (2018)
    • Perry L., Landau S., Flugelman MY., Levenberg S. Genetically engineered human muscle transplant enhances murine host neovascularization and myogenesis. Communications Biology. 1:161. doi: 10.1038/s42003-018-0161-0 (2018)
    • Landau, S., Moriel, A., Livne, A., Zheng, MH., Bouchbinder, E. and Levenberg, S. Tissue-level mechanosensitivity: Predicting and controlling the orientation of 3D vascular networks. Nano Letters. 18(12):7698-7708. doi: 10.1021/acs.nanolett.8b03373. Epub  Nov 26 (2018)

    2017:
    • Marom A., Shor E., Levenberg S. and Shoham S. Spontaneous activity characteristics of 3D “Optonets” Front. Neurosci., 10:602. (2017)
    • 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.
    • Perry L, Flugelman M, Levenberg S, Elderly Patient-Derived Endothelial Cells for Vascularization of Engineered Muscle. Molecular Therapy. 25(4):935-948 (2017)
    • 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)
    • 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)
    • Avesar J., 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)
    • 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)
    • 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. Front. Neurosci. 11:589 (2017)

     

  • Main Research Interests

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

  • Research Topics


    Engineering  blood vessel networks
    In this project we explored the effects of mechanical forces, scaffold type and supporting cells on angiogenesis. We examined different endothelial cells and support cells under various conditions, with a particular focus on  how engineered vessels align in response to mechanical forces, and  integrate in-vivo.     This study was supported by the FP7 ERC starting Grant, Engvasc.
    Engineering Composite Tissues for Facial Reconstruction
    Facial reconstruction usually involves the use of autologous grafts or composite tissue allografts, which are highly complex tissues that pose significant challenges to tissue engineering experts. Tissue engineering of independent facial elements, e.g., bone, adipose, skin and muscle tissues, has been demonstrated. However, to date, no composite soft tissues composed of multiple facial layers have been created. Composite facial tissue engineering will require proper innervation and vascularization, essential to support generation of large thick implants. However, techniques for effective innervation of engineered tissues are currently insufficient and generation of well-vascularized large and thick engineered tissues is still one of the major obstacles limiting their translation to the clinic. Our goal is to engineer thick, composite, human-scale, facial tissues (muscle-adipose-dermis composite, and bone) of a personally adaptable shape, that will be vascularized invitro, and innervated upon transplantation. Our concept is to create in-vitro a functional vascular network (VesselNet), within engineered constructs, which will allow for the generation of thick engineered tissues under continuous flow conditions. 3D bio-printing techniques will be applied to create the engineered tissues. These tissues will serve as a model to study mechanisms involved in vessel anastomosis, and tissue organization and stabilization. This study is supported by the Horizon 2020 ERC Consolidator Grant, VesselNet.
    3D Bioprinting of Pancreatic Tissue
    Developing therapies for pancreatic diseases, such as diabetes and pancreatic cancer, is hampered by a limited access to pancreatic tissue in vivo. Engineering three-dimensional (3D) tissue models, which accurately mimic the native organ, have great potential in biomedical applications, by both providing powerful platforms for studying tissue development and homeostasis and for modeling diseases in pharmaceutical testing. Our research establishes a multi-disciplinary European consortium with the goal of developing an innovative bio-printing approach for generating pancreatic tissue. Tissues and organs comprise multiple cell types with specific biological functions that must be recapitulated in the printed tissue. We aim at bio-mimicking developmental processes to fabricate 3D bio-printed pancreatic tissue units that allow sustained cell viability, expansion and functional differentiation ex vivo. This study is supported by Horizon 2020, FET-Open – Novel ideas for radically new technologies, Pan3D.
      Restoring Insulin Sensitivity in Type 2 Diabetes Patients using Engineered Muscle Tissue
    Type 2 Diabetes (DM2) is a complex metabolic disease, characterized by adipose and muscle insulin resistance accompanied by defects in pancreatic insulin secretion or loss of function of insulin-secreting cells. Present therapeutic modalities include lifestyle modification and pharmaceutical agents, however many patients fail to achieve blood glucose homeostasis. This research proposes to overcome peripheral tissue insulin resistance by genetically modifying skeletal muscle cells and use them to construct engineered muscle tissue. Upon implantation of such engineered muscle, overall glucose uptake of the animal is expected to be enhanced, therefore improving diabetic state. This study is supported by the The Rina and Avner Schneur Center of Diabetes Research (http://schneur-diabetic-center.net.technion.ac.il/)
    Bone Tissue Repair
    The main hurdle in bone tissue repair is maintaining appropriate vascularization for regeneration of large-scaled defects. We fabricate engineered constructs, capable of soft and hard tissue repair. These pre-vascularized composite grafts are fabricated from FDA approved and biocompatable biomaterials, which undergo an induction phase by differential seeding with diverse cellular components. Our bone tissue engineering (BTE) models are treated from a clinical perspective, utilizing in vivo imaging and CAD-CAM interfaces to produce defect-specific grafts. These engineered constructs are implanted in live animal models to assess their ability to regenerate complex anatomical structures. This study is supported by the Israel science foundation.
    Spinal Cord Injury Regeneration
    Spinal cord injured rat after exosome treatment Stem cell-based therapies hold great potential to treat spinal cord injury and additional nervous system traumatic syndromes due to lack of regeneration in the adult nervous system. Our research focuses on delivering stem cells into a complete spinal cord injury. We utilize tissue engineering methods to enhance stem cell integration and survival post implantation. In addition we study the effect of vascularization on spinal cord regeneration. Alternatively, we exploit the regenerative effects of stem cell-derived exosomes as therapeutics and drug delivery platforms to target the spinal cord lesion. This study was supported by the J&J Shervington Fund (SL), and the Israel Foundation for Spinal Cord Injury.  
    Cardiac Muscle Regeneration using a Perfusable Cardiac Patch
    cardiomyocytesThe aim of this project is to create a perfusable cardiac patch, intended for repairing damaged areas of the cardiac muscle. The patch is created using 3D bioprinting technology, which allows for the controlled and automatic deposition of biological and structural materials that will form the construct. Endothelial cells are deposited within an extracellular matrix mimicking material, enabling them to spontaneously organize into vascular networks. Cardiomyocytes are obtained by differentiating induced pluripotent stem cells (iPSCs) and seeded along the endothelial cells, creating a more complex tissue.
    Geometric and Mechanical Patterning of Hierarchical Vascular Networks
    This research focuses on exploring the biophysical factors controlling vascular architecture, remodeling, and integration upon implantation. Using cutting edge methods to pattern the organization of cells, and to map and control mechanical forces within the 3D constructs, the role of cell-generated forces, initial endothelial cell organization and external mechanical forces in the location, orientation and extent of sprouting is studied. In addition, the impact of hierarchical network geometry, rationally designed, on implant integration in-vivo is assessed. This research is supported by United States-Israel BSF grant in collaboration with Prof. Christopher Chen from Boston University.
    Effect of scaffold geometry on vascular networks
    Michigan fibersMany environmental factors can affect the behavior of newly sprouting vessels. Among them, scaffold geometry provides mechanical cues that are translated into chemical and physical cell signaling, which impacts on the decisions made by migrating vessels. This research studies how different scaffold geometries can help control the behavior and orientation of sprouting vessels during network formation. This research is supported by funding from the University of Michigan – Israel Partnership for Research.
     Cell-Grown Meat
    The aim of this project is to produce meat from cell cultures, using tissue engineering techniques. We isolate stem cells from a bovine origin, expand them, and seed them on 3D scaffolds, to develop bovine skeletal muscle tissues. We study food-related properties of bovine skeletal muscle tissues under different cell combinations, scaffolds and media composition. This study is supported by Aleph Frams (Aleph Farms).  
    Nano-liter Microfluidic device
    AST (Antimicrobial susceptibility testing ) system on a microfluidic device capable of delivering results in under 6 hours was developed in the Levenberg’s lab. Using an automated algorithm for data analysis, the system is capable of determining whether bacteria from an infection site is resistant or susceptible to the tested antibiotic. This technology was licensed to Nanosynex, and now-a-days, Nanosynex takes this proof of concept from the lab to the market.