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Project

Unraveling disparate roles of Notch-1 and Notch-2 signaling in bladder cancer.

Funder: Michael Smith Foundation for Health Research

Funding period
CAD 450 K
USD 338 K
Funding amount
Abstract



OBJECTIVE. Bladder cancer is the 5th most common cancer, yet it remains understudied and we are only now making strides in understanding the molecular make-up of this cancer. Recently we and others have discovered that loss of the cell surface receptor Notch-1 drives growth of some bladder cancers, while increased Notch-2 activity drives other bladder cancers. Here we aim to determine how Notch-1 and Notch-2 can lead to such differing effects on cancer growth even though they share many features in common. In addition we aim to design a new drug to inhibit Notch-2 specifically.

SPECIFIC AIMS. To address these objectives, we propose three specific aims:

In our Aim #1 we will create a mouse model that over-expresses Notch-2 specifically in the bladder and we expect this will cause bladder tumours to form. 

In our Aim #2 we will use advanced techniques to study the differences between Notch-1 and Notch- 2 signaling that make them have such different effects. Here we will especially investigate how each Notch protein controls the reading of genes in the cell nucleus.

In the Aim #3 we will develop a new small molecule inhibitor of Notch-2 using computer-aided drug design.


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System

Categories
  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Cancer

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    2.1 Biological and endogenous factors

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science