Our lab studies monogenetic lipid metabolism disorders of the nervous system.

Our laboratory at MGH explores the relationship of mutant genes to specific biochemical defects and their contribution to neurodegeneration. To develop novel treatments, our laboratory assesses the consequences of disease causing genes. A large focus of our efforts lies in advancing new gene therapy trials for rare neurological diseases. This encompasses ex vivo lentiviral and in vivo AAV- based approaches as trials of antisense oligonucleotides.

1. Molecular Insights into Hereditary Sensory Neuropathy Type 1 (HSN1): We discovered a substrate dependence of the lipid accumulation and found it to be specific to vulnerable tissue in the nervous system. These insights helped explain why widely expressed SPTLC1 mutations led to damage of specific structures in the nervous system.
2. Treatment Development and Biomarkers for Peripheral Neuropathies: We discovered the neurotoxic sphingolipids accumulating in type 2 diabetes and extended my work to diabetic polyneuropathy patients.
3. Elucidating the Pathophysiology of Adrenoleukodystrophy: Using both imaging tools and post mortem pathological analysis, I have contributed to the understanding of disease progression and the pathophysiology of adrenoleukodystrophy
4. AAV Mediated Gene Therapy for Adrenomyeloneuropathy (AMN): we are developing AAV mediated gene therapy for AMN using recombinant adenoassociated virus serotype 9 (rAAV9) vector for delivery of the human AB