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Researchers
  • Dr.  Ofra Benny
Dr. Ofra Benny
 
Bioengineering and Nanotechnology for Targeting Angiogenesis and the Tumor Microenvironment (TME)
 
The tumor microenvironment consists of a myriad of cellular compartments, soluble factors, and signaling molecules that support tumor growth and invasion, providing niches for metastases to thrive. Stromal cells including epithelial, endothelial and mesenchymal cells play a central role in tumorigenesis. Compared to tumor cells they are less genetically instable, making them attractive targets for anti-cancer therapy. 
 
Angiogenesis
Angiogenesis, the formation of new blood vessels, is a complex, multistep process that involves expression of proangiogenic growth factors which trigger recruitment of inflammatory cells, remodeling of the extracellular matrix, and endothelial cell processes such as migration and proliferation. Combined, these factors culminate in sprouting of new vessels from preexisting vascular networks.
 
 Tumor-driven angiogenesis a tissue encompassing multifactorial disease
 Tumor-driven angiogenesis ― a tissue-encompassing multifactorial disease.
 
Pathological angiogenesis is a critical component in cancer, in chronic systemic inflammatory diseases such as psoriasis and rheumatoid arthritis, and in ocular conditions including age-related macular degeneration (ARMD), corneal inflammation and diabetic retinopathy. Despite promising therapeutic potential, the clinical efficacy of antiangiogenic drugs remains relatively limited. Using a multidisciplinary approach, combining advanced methods in biomedicine, drug delivery and nanotechnology, we aim to develop novel therapies with improved bioavailability, tissue accessibility, solubility, stability and drug specificity. Our approach utilizes self-assembling, biocompatible polymer constructs for developing improved methods of drug delivery as well as novel nanoparticles with specific drug-release kinetics. We employ multiple cancer and angiogenesis molecular methods, cellular assays, and animal models toward the ultimate goal of finding new therapies for cancer, metastases and other neovascular diseases.
  
micelle formation
 
 
Rational Drug Design
Polymer nanomicelles are composed of di-block copolymer that forms a self-assembled spherical structure, creating a hydrophobic core and hydrophilic shell. Drugs can be conjugated or encapsulated in polymer micelles, thus modifying their properties. This structure provides a platform for better bioavailabilty and tissue targeting.
 
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Targeted Research Topics
 
 

Angiogenesis:

 - Tissue response and resistance to anti-angiogenic therapy

 - Rational drug combinations

 - Nanotechnology-based anti-angiogenic drugs

 - MetAp2 inhibitors - broad spectrum anti-angiogenic drugs

 - Ocular drug delivery systems for treating neovascular eye disease

 

Bioengineering:

 - Degradable implantable devices

- "Tumor-on Chip" microfluidic devices

- 3-D tissue and tumor models

 - Microfluidic droplet fabrication


Drug delivery and Nanomedicine:

 - Polymer micelles and Solidified Polymer Micelles (SPMs)

- Emulsion-based degradable polymer nano/micro-particles

 - Layer-by-layer encapsulation

 - Mechansims of cell uptake of drug carriers

 - Dermal drug-delivery 

- Ocular drug delivery






 
Available Positions
 
Ph.D and Postdoctoral Positions in Nanotechnology, Cancer and Angiogenesis
M.Sc, PhD and postdoctoral positions are available for excellent candidates. Our laboratory focuses on development of novel anti-cancer and antiangiogenic therapeutics utilizing nanotechnology and bioengineering.
 
Students joining our laboratory will gain extensive expertise in several techniques including: tissue culture and cell-based assays, molecular biology, animal models of angiogenesis, ocular diseases, cancer and metastases, imaging and microscopy, histology, drug encapsulation and polymers.
 
Successful applicants should be highly self-motivated, work well within a team, and have critical and independent thinking abilities. Previous research experience and strong English skills are distinct advantages.
 
Contact: Interested candidates should apply by email, submit a CV, record of studies, and contact information of three references.
 
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 Brief CV
 
Senior Lecturer - Institute for Drug Research (IDR), The Hebrew University of Jerusalem (2013-current)
Instructor - Harvard Medical School, Vascular Biology, USA (2010-2013)
Research Associate - Boston Children’s Hospital, Vascular Biology, USA (2010-2013)
Postdoctoral Fellow- Harvard Medical School. Boston Children’s Hospital, Vascular Biology. Advisor: Robert D’Amato, MD, PhD. (2008-2010)
Postdoctoral Fellow- Harvard Medical School. Boston Children’s Hospital, Vascular Biology. Advisor: Judah Folkman, MD (2007-2008)
M.Sc / Ph.D. - Technion- Israel Institute of Technology. Biotechnology Engineering, (2001-2007) Advisor: Marcelle Machluf, PhD.
B.Sc. - Technion- Israel Institute of Technology, Biotechnology Engineering (1996-2001)
Selected Publications
 
 
 
Benny O*, Fainaru O , Adini A , Bazinet L , Adini I, Cassiola F, Pravda E, Koirala S , D'Amato R, Corfas G , Folkman J. An orally delivered small-molecule formulation with antiangiogenic and anticancer activity. Nature Biotechnology 26:799-807 (2008) (Journal Cover) *Corresponding author
 
Benny O, Kim SK, Gvili K, Radzishevsky IS, Mor A, Verduzco L, Menon LG, Black PM, Machluf M, Carroll RS. In vivo fate and therapeutic efficacy of PF-4/CTF microspheres in an orthotopic human glioblastoma model. FASEB J. 22:488-99 (2008).
 
Benny O*, Pakneshan P. Novel technologies for antiangiogenic drug delivery in the brain. Cell Adhesion and Migration 6;3(2) (2009) Invited review  *Corresponding author.
 
Benny O*, Nakai K, Yoshimura T, Bazinet L, Akula JD, Nakao S, Hafezi-Moghadam A., Panigrahy D, Pakneshan P,  D’Amato R, Broad spectrum antiangiogenic treatment for ocular neovascular diseases. PLoS ONE, 5:e12515 (2010) *Corresponding author.
 
Benny O, Menon L, Goren E., Kim SK, Black P, Carrol RS, Machluf M. Local delivery of PLGA microspheres containing imatinib mesylate inhibits glioma growth. Clinical Cancer Research 15:1222-31 (2009).
 
Arai T, Benny O, Joki T, Menon LG, Machluf M, Abe T, Carroll RS, Black PM. Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes. Anticancer Research 30:1057-64 (2010). 
 
Adini A, Adini I, Ghosh K, Benny O, Pravda E, Hu R, Luyindula D, D'Amato RJ.The stem cell marker prominin-1/CD133 interacts with vascular endothelial growth factor and potentiates its action. Angiogenesis. 2012 Nov 13. [Epub ahead of print]
 
 
Panigrahy D, Edin ML, Lee CR, Huang S, Bielenberg DR, Butterfield CE, Barnés CM, Mammoto A, Mammoto T, Luria A, Benny O, et al. Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. Journal of Clinical Investigation (JCI) 2012 3;122(1):178-91.
        
Contact Information
 
Dr. Ofra Benny
The Institute for Drug Research
School of Pharmacy
Faculty of Medicine, Ein Karem
The Hebrew University of Jerusalem
Jerusalem, 91120 Israel
 
  
 
The importance of a hypothesis is measured not by how long it lives; but by how much good it generates.” – Judah Folkman (1933-2008)

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