Liver Disease | Overview
The liver is an organ essential to digestion, energy metabolism and filtration of poisons from the body. Diseases, such as hepatitis and liver cancer, can put a child’s life at risk. Liver transplants are often an important component to treatment, but unfortunately, there aren’t enough donor livers to help every child.
The liver is one of the few organs in the body where differentiated adult stem cells can divide to regenerate after an injury. At Boston Children's Hospital, researcher Fernando Camargo, PhD, is investigating the different processes that promote liver regeneration and healing.
One set of molecules Camargo studies extensively is the Hippo pathway, which is a system within cells that ultimately controls growth and decides how large an organ becomes. When functioning normally, the Hippo pathway is important to cell growth, but when malfunctioning, the Hippo pathway can also play a role in diseases such as liver cancer and liver fibrosis. Studying the Hippo pathway can help scientists develop treatments which encourage a liver to heal itself, allow scientists to grow liver cells in the lab (a therapeutic approach not yet available) or study the development of liver cancer. The Camargo lab has recently identified chemicals that control Hippo signaling, which could be turned into novel treatments for liver cancer and other liver diseases.
Investigating cellular histories using DNA barcoding
The human body is derived from a single cell. One of the goals of many stem cell biologists is to trace the cell as it divides, acquires specialized features, and gives rise to a highly complex multicellular organism. Obtaining this information would be akin to having a family-tree, where cells represent the branches in this tree. If comprehensive whole-organism family trees could be assembled, researchers would learn a lot about human fetal development, genetic diseases and more.
Until recently, it was impossible to look deep into development and record this lineage tree information at a single cell resolution. The Camargo lab has been a pioneer in developing tools that allow the tracing of cellular histories. His group has developed cellular barcoding methodologies that allow for a unique genetic label to be embedded in the cells’ DNA. This barcode can be read by another technique called single cell RNAseq, which gives molecular information of each cells — the cell biography.
With this information, the Camargo lab is attempting to generate and understand family trees of laboratory mice and humans. They have applied this technology to generate family trees of blood development and blood regeneration. They have discovered novel genes that control blood forming stem cells and uncovered new cell populations that produce platelets. They are now utilizing barcoding technologies to generate family trees of cancer and aging models to understand the ancestry and the function of the cells involved in these diseases.