Knouse Lab

The Knouse Lab aims to discover the molecular secrets that make organ regeneration possible, enabling a future where we can grow and repair any organ in the body.

Every year, millions of people suffer from diseases of irreversible organ damage, including neurodegeneration, stroke, heart attack, and diabetes. All of these diseases owe their lifelong morbidity to the loss of specialized cells required for organ function, and the inability of organs like the brain, heart, and pancreas to replace these cells. A means of stimulating these organs to regenerate would provide much-needed cures for numerous debilitating conditions. Unfortunately, despite decades of effort, this longstanding goal of regenerative medicine remains elusive to this day.

In pursuit of this goal, the liver emerges as a remarkable and highly informative exception to other organs. Unlike all other solid organs, our liver can completely regenerate itself after damage. Following liver injury–even injuries that exceed over half of liver mass–the liver’s remaining specialized cells re-enter the cell cycle and proliferate to restore liver size and function in a matter of days. The liver thus harbors the secrets for how to make an organ regenerate, and offers the exciting possibility that by learning these secrets we could someday engineer other organs to do the same.

Although the liver’s remarkable regenerative capacity has been appreciated for decades, we still do not fully understand how the liver is able to regenerate itself when all other organs cannot. Answers to these questions have been limited in part by a lack of tools to investigate regeneration in the living organism. Our lab’s mission is to gain molecular insight into the differential regenerative ability of mammalian organs so that we can modulate the regenerative capacity of any organ in the setting of disease. To this end, we are pursuing two parallel but complementary agendas. First, we are developing tools for high-throughput functional genomics in living mice to bring experimental tractability to these longstanding questions. Second, we are leveraging these new technologies alongside other approaches to uncover the molecular rules governing permissive and restrictive contexts for regeneration. By uncovering the molecular switches that control regeneration throughout the body, we aim for a future in which diseases of organ damage are readily cured.