Dr. Tifft's research focuses on lysosomal storage disorders (LSDs), particularly those that affect the central nervous system. With more than 20 years of experience as a clinical geneticist, Dr. Tifft is expert in the diagnosis and treatment of LSDs. In collaboration with colleagues at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), she is using mouse models to elucidate the pathophysiology of disease progression in a number of these conditions.
Her research has shown neurodegeneration to be an inflammatory process involving the activation of microglia and astrocytes, a process that can be slowed by bone marrow transplantation or treatment with small molecules such as migluatat and other selected anti-inflammatory agents. Her findings are directly applicable to the study of two LSDs in particular - Tay-Sachs and Sandhoff diseases - and have been extended to other glycosphingolipid storage disorders, including GM1 gangliosidosis.
Tay-Sachs disease is an autosomal recessive disorder caused by a deficiency of the enzyme hexosaminidase A, which leads to the accumulation of a lipid called GM2 ganglioside, predominantly in brain tissues. Incidence had historically been high among Ashkenazi Jews, but effective carrier screening introduced in the mid-1970s has reduced incidence in this group by more than 90 percent. Currently, only a third of the 20 to 25 patients diagnosed with Tay-Sachs each year in the United States are of Jewish heritage.
In the classic infantile form of Tay-Sachs disease, a child experiences normal development for the first six months, reaching a plateau in skills development and the onset of seizures usually before the child's first birthday. Relentless neurodegeneration continues, leading to death between two and five years of age. Sandhoff disease and GM1 gangliosidosis are related ganglioside storage disorders that have no strong ethnic predilection. There are no effective therapies for these diseases.
Dr. Tifft is conducting an ongoing natural history study of glycosphingolipid storage disorders to identify biomarkers in cerebrospinal fluid and other tissues that correlate with disease progression. She applies her knowledge of biomarkers and disease progression as a member of the Scientific Advisory Group for the Tay-Sachs Gene Therapy Consortium, where she designs outcome measures for clinical trials that use gene therapy and other therapeutic modalities.
Dr. Tifft also is interested in diagnosis and surveillance of children with neurofibromatosis type 1. Her clinical research has shown that screening with magnetic resonance imaging of the brain in newly diagnosed patients detects clinically significant pathology prior to the onset of symptoms.
She has participated in multi-center clinical trials of enzyme replacement therapy for the treatment of Gaucher, Fabry, and Pompe diseases and has recently completed an investigator-initiated study on the treatment of GM2 gangliosidosis using substrate reduction therapy.
Dr. Tifft serves as the Director of Pediatrics for the NIH Undiagnosed Diseases Program. In this role, she applies her expertise in cell biology and storage disorders to design screening assays of tissues from patients referred to the program. Her study of structural abnormalities in lysosomes and other cellular organelles is applied in combination with other functional and gene sequencing studies to heighten the potential for identifying new diseases.
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Last Reviewed: August 19, 2013