Researcher Profiles
Michelle Robinette, M.D., Ph.D.
2024 Funding recipient
Identifying and modeling genetic drivers of systemic inflammatory diseases in MDS
EvansMDS Young Investigator Award 2024
PROJECT SUMMARY
Myelodysplastic syndrome (MDS) is a group of diseases of blood and immune cells that often have genetic problems, called mutations. For many years, researchers have observed that patients with MDS have more systemic inflammatory and autoimmune diseases (SIAD) than the general population. Why exactly this happens and how best to treat are not well understood. In the past several years, researchers have found that some mutated blood cells can use inflammation signals to grow. A new mutation in UBA1 was also discovered that can cause both severe SIAD and MDS. Together, these findings suggest that better understanding of SIAD that occur in MDS may also help understand and possibly treat MDS, as well as connected SIAD, which are the goals of this research.
I will study the link between MDS and SIAD using two approaches focused on inflammation. First, because almost all people with UBA1 mutations develop SIAD, I have made a mouse model to study how the mutant immune system can cause inflammation in many different organs. Because mice and humans can be different, I will also compare these results to a new human cell line model. It is very unlikely that everyone with SIAD and MDS has a UBA1 mutation. So, in the second approach, I will study people who have MDS to determine what proportion of people have UBA1 mutations and if there are other mutations linked to other patterns of SIAD.