Susan A. Slaugenhaupt
Department of Neurology (Genetics)
Center for Human Genetic Research
Simches Research Center CPZN-5254
185 Cambridge St.
Boston, MA 02114
Lab Members: 3 postdoctoral fellows, 2 technicians
Visit my lab page here.
The overall goal of the Slaugenhaupt lab is to bring the study of genetic disease full circle: from the initial collection of family data, to the cloning and characterization of the culprit gene, and back to the patient via development of improved diagnostics and effective therapies. The work in the lab is currently focused on two neurological disorders, familial dysautonomia and mucolipidosis type IV, and the common cardiac disorder mitral valve prolapse.
mRNA slicing and human disease: Our work on the genetics of familial dysautonomia led to the discovery of a unique mRNA splicing mutation that results in tissue-specific aberrant splicing. Given that patient cells retain the capability to make normal IKAP protein, we sought to identify potentially therapeutic compounds that alter mRNA splicing. Kinetin, a plant cytokinin, dramatically increases normal protein in patient cells and work is currently underway to test this drug as a potential therapeutic agent for FD patients. We are now focused on the characterization of the aberrant splicing mechanism and discovery of methods to correct it. Two mouse models have also been developed to study both normal IKAP function and as well the basis of tissue specific alternative splicing.
Mucolipidosis type IV: MLIV is a devastating lysosomal storage disease with severe neurologic and ophthalmologic deficits. The gene that causes MLIV was cloned in the lab and we have shown that the protein functions as a calcium permeable cation channel that has a role in lysosomal exocytosis and protein recycling. We are currently using animal models, cellular models, and gene expression and pathway analysis in order to both understand the pathogenesis of MLIV and develop therapies.
Mitral valve prolapse: The lab is working to understand the genetic basis of MVP, a very common cardiac disorder. I began working with Dr. Robert Levine in the MGH Echocardiography lab in 1997 and together we have collected numerous families segregating MVP and have identified two novel MVP loci on chromosome 11 and 13. Work is currently underway to clone the culprit genes, and new families are being enrolled in order to identify additional loci for this genetically heterogeneous disorder.
For a complete listing of publications click here.
Last Update: 1/4/2013