Currently, Dr. Lewis is studying the molecular biology of SIOD, particularly focusing on the relationship between shortened telomeres and this disease, and also other aspects of why and how the mutation that causes the disease—in the SMARCAL1 gene—affects the body. To do this, the research team is using a variety of imaging and sequencing tools available at Stanford and tissue samples, blood, and data from patients with and without SIOD.
These tools allow the team to study and compare the molecular landscape of the disease to determine how certain cells in people with SIOD are different from the cells of people without it. For instance, Dr. Lewis’s research used cells donated by Kruz and Paizlee to show that the T cells of SIOD patients have shortened telomeres, the special protein cap that keeps chromosomes from getting damaged when a cell divides. In addition to studying shortened telomeres, Dr. Lewis is now setting up collaborations at Stanford to look at the origin of DNA replication in SIOD patients and healthy controls.
For decades, researchers looked for the precise locations in mammalian genes where DNA replication begins. Recent tools and techniques have allowed them to identify and map tens of thousands of DNA replication origin sites and examine their genetic and epigenetic features. By looking at molecular activity at these origin sites in tissue samples from people with SIOD, researchers can match changes to specific disease symptoms with the aim of directing or creating treatments that can slow or halt replication stress or DNA damage.