The Gumbiner Lab studies how tissues and organs are built from collections of individual cells. This leads to discoveries about how animals and humans develop, and how their tissues are maintained, repaired and regenerated throughout life. Understanding how these biological processes malfunction provides insights into the causes of birth defects and many diseases, and approaches for potential new treatments.
Unraveling how cells bind together
Our current research focuses on understanding the complex process that governs how cells adhere to each other. This process tells cells when to bind tightly together – and when to let go and move around – so they can either maintain the tissue structure or remodel and reshape it.
We are unraveling how this process is regulated and controlled by specialized adhesive proteins on the surface of the cell called cadherins. For example, we made key discoveries about how proteins inside the cell – called catenins – control the cadherins in response to signals from the environment. Together these proteins help the cells shape the architecture of tissues and organs.
Our discoveries in these areas help scientists understand not only how tissues and organs develop normally, but also how birth defects or diseases arise when adhesion malfunctions. Strong loss of adhesion allows tumor cells to escape into other parts of the body to cause metastases. Subtler adhesion defects can lead to leaks in barriers formed by tissues, such as the linings of the gut and lungs that control whether immune cells can enter an organ and attack microbes that live there. Such defects can contribute to the development of inflammatory diseases and sepsis.
Studying a key pathway
As a tissue or organ forms, the Hippo pathway tells the cells when to stop growing. We discovered that cadherin adhesion proteins stimulate the Hippo pathway to inhibit cell growth when the cells come into close contact with each other. We also discovered that factors in the blood known to stimulate cell growth work in part by inhibiting the Hippo pathway. This allows the cells to grow despite the cadherins trying to inhibit it as the tissue forms.
We are pinpointing how the Hippo pathway functions and how it is controlled in opposite ways by cadherins and growth-promoting factors. Insights into these processes will serve the long-term goal of developing ways to control cell growth: on the one hand to stimulate tissue and organ regeneration by blocking the Hippo pathway; on the other hand to inhibit growth of cancer cells.
Laying the foundation for innovative therapies
Some of our newest research focuses on finding ways to control cell adhesion. We are creating antibodies that tighten the junctions between cells and stop them from pulling apart. While this work is still in the early stages, it could lead to new ways to slow cancer metastasis by stopping cells from drifting away from each other and by enhancing the sealing of tissue barriers to prevent leaks associated with inflammation.