Grant: Doctoral: Vanier Canada Graduate Scholarships

Lymphangioleiomyomatosis (LAM) is a rare lung cancer that predominantly strikes women during reproductive years. In LAM patients, cancerous cells invade the lungs, causing destruction of essential tissue and leading to respiratory failure. LAM is driven by genetic mutations which alter molecular pathways and allow the LAM cancer cells to grow, live longer, and cause severe damage. Unfortunately, the current treatment regime for LAM has limited efficacy and is unable to rid patients of disease. Thus, the goal of this project is to develop an improved therapeutic option. I additionally seek to better understand the molecular pathways driving the cancerous properties of LAM cells. Recently, it was discovered that blocking the protein CDK2 can kill LAM cells and prevent cancerous invasion. While CDK2 is commonly known for its involvement in cell replication, its role in invasion remains elusive. I will better understand the function of CDK2 in LAM invasion by deleting this gene and examining changes in the LAM cells' cancerous abilities. Using molecular and computational techniques, I will explore the array of genes and proteins that effect, and are affected by, CDK2. Equipped with an improved understanding of LAM invasion, I will then investigate a new LAM treatment option by testing a Health Canada-approved drug which blocks CDK2. First, I will inject human LAM cells into mice to create an accurate model of the disease. I will then treat the mice with the drug to assess therapeutic efficacy. Changes in mouse lung function and the extent of LAM cell elimination will be measured. The anticipated success will allow this treatment to be rapidly brought to human clinical trials. This work will lead to a better understanding of the cause of LAM cancerous invasion and its connection to the cell cycle system. Importantly, this project will rapidly advance essential therapeutic options for LAM patients and provide key insights into cancer and other invasive diseases.