Year: 2018

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

Bladder cancer is the fifth most common cancer, yet it remains understudied and we are only now making strides in understanding it’s molecular make-up. 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 growth of 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. From this we aim to design a new drug to inhibit Notch-2.

We will:

  • Create a mouse model that over-expresses Notch-2 in the bladder. We expect this will cause bladder tumours to form.
  • Use advanced techniques to study the differences between Notch-1 and Notch- 2 signaling that make them have such different effects. We will especially investigate how each Notch protein controls the reading of genes in the cell nucleus.
  • Develop a new a new drug to inhibit Notch-2 using computer-aided drug design.

End of Award Update – April 2024

 

Results

We have identified a candidate Notch-2 inhibitor that requires further testing in pre-clinical models before potential testing in patients with bladder cancer.

 

Impacts

Our work has explained an important pathway that drives growth and progression of bladder cancer in some patients.

 

Potential Influence

This new inhibitor could represent a novel way to treat bladder cancer.

 

Next Steps

We will publish the results on Notch when completed.

Improving outcomes through precision medicine for adults with primary immunodeficiency

Primary immunodeficiencies (PIDs) are a group of conditions in which part of the immune system is either missing or does not function normally. Those affected by PIDs may suffer from recurrent infections, autoimmune disease (where the immune system attacks the body's own tissues), and certain cancers. These conditions are not rare; affecting 1:2,000 to 1:10,000 people, with nearly half of cases diagnosed in adulthood. Too often, adults with PIDs undergo a painful journey that spans decades in search of a diagnosis. Without knowing the cause of their immune deficiency, adults with PIDs may not receive life-changing treatment. 

Our research program will address these challenges using precision medicine: an exciting way of identifying the cause of the disease and finding treatments that specifically target the underlying problem. We will perform next generation sequencing, a method to quickly read genetic material, on adults with PIDs where the underlying cause is undiagnosed. If a new change in a gene (mutation) is identified, we will perform specialized experiments to prove that the mutation is indeed responsible for the patient's symptoms. We will then look for targeted treatments to address the specific cause of that patient's illness. 

By harnessing the power of personalized genetics and precision medicine, our goal is to improve outcomes for adults suffering from PIDs.