State: North Carolina

Funded by the Stuart Scott Memorial Cancer Research Fund

The human gut contains trillions of bacteria. In fact, there are more bacteria in the gut than there are cells of the human body. To protect the body from gut bacteria, immune cells constantly battle with gut bacteria. This battle occurs inside every person but in some, this battle can cause tumors to grow. Tumors often grow in the colon and this type of cancer, called colorectal cancer, is the location where most gut bacteria dwell. How can the battle with gut bacteria cause colon tumors to grow? To answer this question we must first find out which immune cells control and design the battle plan.
We think that the battle plan against gut bacteria is designed by a special immune cell, the dendritic cell. There are many different types of dendritic cells and we found that each has a different battle plan. We want to find out which dendritic cells enter colon tumors, which dendritic cell’s battle plan cause tumors to grow, and which battle plan may help fight the tumor. When colon tumors grow we think that gut bacteria force the dendritic cell to make proteins that shield the tumor from attack and help the tumor to grow. We are testing these ideas by changing how dendritic cells respond to gut bacteria, to find out how this changes the battle plan, and to discover how this impacts colon cancer.

Following surgery and treatment, breast cancer patients live with a high risk of developing a relapse. When tumors do recur, especially at distant sites, they are often incurable. Therefore, it is important to develop new approaches for preventing breast cancer relapse. The period between treatment of the primary tumor and the formation of a recurrent tumor is called dormancy. During this stage there are cancer cells somewhere in the patient’s body that are dormant, or not actively growing. These dormant cells are the source from which recurrences must arise. Understanding how these cells survive for long periods and designing ways to kill them is important for preventing recurrences.

Dormant tumors cannot be detected by current imaging methods, and so studying these cells in patients is difficult. We have developed mouse models that allow us to study dormancy and recurrence. Using these models, we have found that dormant tumors have a unique type of metabolism. In order to translate this finding to a potential therapy it is important to know more about this metabolism works, and whether dormant cells can be killed by targeting this metabolism. In this proposal we will use the mouse models we developed to address these questions. Once we understand more about dormant cell metabolism, we may be able to design drugs that can kill dormant cells and prevent breast cancer relapse.