NERF and ELF-1 as Novel Transcriptional Mediators of Angiogenesis and Therapeutic Drug Targets (BIDMC 541)

Category:    Drug Discovery Tools

KeyWords:  Angiogenesis;  Inflammation;  Cancer;  

BIDMC ID:    541

Abstract:

ELF-1 and NERF-2 are members of the Ets family of transcription factors. Conserved Ets binding sites have been identified in the promoters of many vascular specific genes, including Tie1, Tie2, and Flt-1 and play a central role in regulating genes involved in cellular development, differentiation and proliferation. Drs. Libermann and Oettgen have shown that ELF-1 and NERF-2 transactivate vascular-specific expression of the Tie2 gene and that ELF-1 and NERF-2 genes are upregulated during angiogenesis in an angiogenesis model. Drs. Libermann and Oettgen have developed methods for diagnosing, monitoring and treating diseases such as cancer, diabetic retinopathy and coronary heart disease by altering blood vessel development and/or endothelial cell differentiation. Additionally, they have developed methods to screen for compounds that alter the activity of the transcription factors ELF-1 and NERF-2.

Inventor:   Towia Libermann, Ph.D. and Peter Oettgen, M.D.

Commercial Opportunity:

The commercial opportunity for this technology includes the treatment of cancer and diabetic retinopathy in an anti-angiogenic manner as well as utilizing the technology in a pro-angiogenic manner to treat coronary heart disease.

Competitive Advantages:

The major shortcomings of the currently available anti-angiogenesis drugs are that they do not completely block angiogenesis. Targeting ELF-1 and NERF may be more effective or be an additional method of blocking angiogenesis because these targets are only expressed in an activated state.

Related Publications:

Dube et al (2001) ELF-1 is a transcriptional regulator of the Tie2 gene during vascular development.  Circulation Research. 88:237-244.

Iljin K et al. (1999) Role of the Ets factors in the activity and endothelial cell  specificity of the mouse Tie1 gene promoter.  FASEB Journal 13: 377-386.

Dube A, et al. (1999) Role of the Ets factor NERF in regulation of the vascular specific Tie 2 gene.  Circulation Research. 84: 1177-1185.

State of Development:

Proof of concept in a cell model of angiogenesis.  Additionally cell-based assays have been developed to enable screening for therapeutic compounds that specifically target ELF-1 and NERF-2.

Related Technology URL:

Patent Status:

US and foreign applications pending.

TVO Contact Info:
     Stanley C Mah
     Senior Associate TVO
     smah@bidmc.harvard.edu
     Phone: 617-667-0573   Fax: 617-667-0646

     Beth Israel Deaconess Medical Center
     Technology Ventures Office  Room: BR-0200
     330 Brookline Avenue
     Boston, MA 02215