State: Ontario

Vintner Grant funded by the V Foundation Wine Celebration in honor of Leslie Rudd and Family

Cancer is one of the leading causes of death across the globe. Early cancer detection can facilitate effective treatment and fewer side effects to improve patient survival and quality of life. Therefore, there is tremendous interest in using recent technological advances in DNA sequencing, medical imaging, and machine learning methods to enable early detection efforts in cancer. Early detection efforts are likely most effective among individuals genetically predisposed to cancer. Moreover, DNA mutations during the aging process can also increase the risk of developing cancer. Therefore, we aim to use population-level sequencing data to build computational methods to assess individualized risk for developing cancer. We envision that the proposed approach will provide novel insights into the role of inherited and acquired DNA mutations toward tumor growth in high-risk individuals. These insights can be employed to facilitate early detection efforts in cancer.

Immunotherapy is a type of cancer treatment that uses the body’s own immune system to fight and destroy cancer cells. Despite its success in treating a number of cancers, immunotherapy has had a limited impact on the treatment of blood cancers, known as leukemia. While there are many reasons for this, a primary reason is the current lack of understanding of how the cells of the immune system interact with leukemia cells. Present knowledge of the types of immune cells that live in the bone marrow and their behavior at various stages of leukemia are almost entirely lacking. To address this, we will perform a widespread analysis of immune cell composition and function during leukemia disease progression. We will use cutting-edge technology to understand the biological mechanisms that become altered during leukemia, which may cause immune cells to promote the cancer’s initiation and relapse. These studies would enable the identification of “immune signatures” associated with different stages of cancer development. The findings will lay the groundwork for our understanding of the bone marrow immune landscape in the context of the human disease. We envision that these studies will fundamentally lead to new treatment strategies for this devastating cancer and thereby improve patient outcomes.  

In the last three decades, no new drugs that can effectively treat pancreatic cancer have been found. One of the major problems in pancreatic cancer is that most research is performed on patients where the cancer has not spread to the rest of the body. This is because these patients are eligible for surgery and researchers have access to the tissue for experiments. However, most patients with pancreatic cancer are diagnosed when the disease has already spread. Patients where the disease has spread do very poorly compared to patients where the disease has not spread. We believe that there are changes in the cancer’s DNA that cause the disease to spread.  

To investigate this, our laboratory compared the DNA from patients where the disease had or had not spread, and found that a gene that can potentially promote the spread of this cancer. This gene, named KRAS, multiplies in patients where the cancer has spread. Patients where this gene has multiplied are very resistant drugs used to treat this cancer. The goal of our project is to understand how the multiplication of this gene is related to therapy resistance. Using specialized techniques in our laboratory, we will grow tumor cells from patients with and without multiple copies of KRAS to figure out changes in the cell that are related to this specific genetic change. We intend to use this information to find new drugs to treat patients where the cancer has already spread.