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CMCC 2295

DEPTOR as a target for the treatment of chronic inflammation and angiogenesis-dependent diseases

Inventors: David Briscoe

Invention Types: Therapeutics

Research Areas: Cardiovascular/Cardiology, Immunology

Keywords: Drug Discovery

For More Information Contact:  Caron, Connie

 

Invention Description:

Researchers in Dr. Briscoe’s laboratory have demonstrated that DEPTOR, DEP domain containing mTOR interacting protein, is expressed in microvascular endothelial cells (EC) and functions as an upstream regulator of EC activation responses and EC-dependent proinflammatory responses.

Using a transgenic mouse model in which intracellular DEPTOR expression can be manipulated and sustained, Dr. Briscoe’s lab have now shown that DEPTOR functions in a similar manner in T-cells. By forcing expression of DEPTOR, they observed that T-cells remained quiescent typical effector function was not achieved. To modulate DEPTOR, they discovered that a small molecule inhibitor of a Cullin ligase that controls DEPTOR degradation can also target DEPTOR in T cells and this compound allowed DEPTOR to remain overexpressed in both EC and T cells. This suggests that families of such molecules may serve as a potent anti-inflammatory agent that sustains DEPTOR levels and its regulatory effects on downstream signaling pathways.

Applications:

• Novel treatment pathway for chronic inflammatory or angiogenesis-dependent disorders

Business Opportunity:

• Sponsored research opportunity

Key Publications: • Bruneau S, et al. DEPTOR regulates vascular endothelial cell activation and proinflammatory and angiogenic responses. Blood. 2013 Sep 5;122(10):1833-42.
• Wedel J, et al. Deptor modulates activation responses in CD4+ T cells and enhances immunoregulation following transplantation. Am J Transplant. 2018 Jul 3. [Epub ahead of print]

IPStatus: Not applicable