My research aimed at developing targeted therapeutic approaches for inherited human diseases.

My research focuses on two neurological disorders, familial dysautonomia (FD) and mucolipidosis type IV (MLIV), as well as the common cardiac disorder mitral valve prolapse (MVP). Our work is focused on gene discovery and therapeutic development, specifically targeting mRNA splicing.  As Scientific Director of the Mass General Research Institute, I work on supporting investigators and promoting research at the hospital.  In 2020, I was named the Elizabeth Riley and Dan E. Smith, Jr. Endowed MGH Research Institute Chair.

1. Unrevealing the pathogenetic mechanism underlying sensory and autonomic loss in familial dysautonomia (FD). FD is caused by a splicing mutation in ELP1. We are working on understanding why some sub-populations of neurons are more sensitive to ELP1 loss than others and on identifying the specific molecular pathways that lead to disease manifestations.
2. Developing a splicing targeted therapy for FD. My group, in collaboration with PTC Therapeutics Inc., has developed a series of compounds that are able to correct the splicing defect responsible for FD. We are now working with the FD Foundation to bring a new treatment to patients.
3. Developing a gene therapy approach to target retinal degeneration and neuroinflammation in mucolipidosis type IV (MLIV) (in collaboration with the laboratory of Dr. Yulia Grishchuk). MLIV is a devastating neurologic disease that leads to severe psychomotor and mental retardation, and progressive retinal disease. Our goal is to develop a gene therapy approach to target both retinal and CNS dysfunctions.
4. Understanding the etiology of the common cardiac disorder mitral valve prolapse (MVP). MVP is a common cardiac valve disease that affects nearly 1 in 40 individuals. Despite a clear heritable component, the genetic etiology leading to non-syndromic MVP has remained elusive. We have identified a novel missense mutation in DCHS1 and we are working on better understanding MVP pathogenesis for future therapeutic development.