Dr. Shahrzad Bahrampour , Ph.D

The Hospital for Sick Children

Unconventional role of volume-regulated anion channel in pediatric brain tumor

Grant Sponsor

Funded by #ColbyStrong

The brain is the most complex organ and has a unique defense mechanism, the blood-brain  barrier. This barrier protects the brain by limiting the entry of harmful agents from blood.  However, that also makes it difficult for therapeutic agents to penetrate, which is a major  obstacle in brain tumor therapy. In theory, a targeted ‘leak’ in the blood brain barrier would  allow therapeutic agents to better access tumors in the brain. With her Powered by Pablove grant, Dr. Bahrampour aims to understand how a very specific kind of leak in the blood brain barrier can be manipulated and clarify its  therapeutic potential for kids with medulloblastoma. 

 

In Dr.  Bahrampour’s own words:

Medulloblastoma (MB) is the most common brain tumor in children. Standard treatment for MB includes surgery, chemotherapy, and radiation. However, the tumor and treatments often cause severe side effects, diminishing survivors’ quality of life. Thus, novel therapeutic approaches are urgently required to provide better treatment for MB.

The brain is the most complex organ and has a unique defense mechanism, the blood-brain barrier (BBB). The BBB occurs between the smallest blood vessels, capillaries, and brain tissue. BBB protects the brain by limiting the entry of harmful agents from blood. However, BBB also has low permeability to most therapeutic agents, which makes it a major obstacle in brain tumor therapy.

I found that ion channel LRRC8A is abundantly present in MB cells. I discovered that loss of function of Lrrc8a in MB changes the behavior of tumor cells by which they attack capillaries and eventually lead to a leakier barrier between blood and tumor (BTB). Thus, I hypothesize that targeting Lrrc8a makes BTB more permeable, increasing tumor access to therapeutics and enhancing MB’s therapeutic response. This project aims to establish the role of Lrrc8a in regulating BTB permeability in MB, reveal its cancer-specific mechanism of action, and define the therapeutic efficacy of disrupting this channel to enhance MB treatment. By defining the utility of this therapeutic molecule in treating MB, my project may bring to light a new targeted treatment for MB patients.

Awarded in 2022