Daniel Wallman, MD

(PCD) is a rare, inherited disorder. It affects cilia, tiny hair-like organs that help the body clear mucus. It is caused by variants in more than 50 genes and lacks targeted therapies to treat it. Our goal is to develop a novel platform to determine the disease-causing capacity of high-priority genetic mutations involved in PCD in understudied populations. We will study variants in four genes that are highly prevalent in understudied non-Caucasian populations where PCD is estimated to be more prevalent than currently observed. We will then study RNA differences in lung cells caused by these variants using single-cell RNA sequencing. These findings will provide the foundation needed to make it easier to confirm that a person has PCD, better understand the genetic underpinnings of the disease, and create human models of PCD that lead to therapy.

Update: We used technology called the induced pluripotent stem cell (iPSC) platform to help diagnose the rare lung disease called primary ciliary dyskinesia (PCD). We studied an individual with symptoms of PCD and a genetic variant of unknown significance in the gene MCIDAS. Using gene editing, stem cell models, and lab tests, we showed this variant causes a failure in cilia development, confirming it as disease-causing. This is the first time iPSCs have been used to confirm a genetic diagnosis for a lung disease.