About
Biography
As a postdoctoral trainee at Cincinnati Children’s, I became inspired by my mentor and by work on patient-related projects. These experiences led me to my current research interest in the molecular pathogenesis of and treatments for lysosomal storage diseases.
In our lab, we are working to understand the pathogenesis of Gaucher disease and other lysosomal storage diseases so that we can develop specific therapies. My research interests include glycosphingolipids metabolism in neurodegenerative disease, specifically lipidomics and transcriptome to the relationship of Gaucher disease and Parkinson’s disease. We also study pharmaceutical small molecule therapy and brain organoid modeling of Gaucher disease. Our research is supported by the National Institutes of Health, foundations and industry-sponsored programs.
We investigate the therapeutic value of induced pluripotent stem cell-derived neural progenitor cells on Parkinson’s disease by increasing lysosomal acid β-glucosidase. We are also exploring the role of progranulin, a novel factor of acid β-glucosidase, as a potential therapeutic treatment of Gaucher disease.
Our recent published research work includes a 2019 study in Human Molecular Genetics outlining a noninvasive cell therapy for neurogenerative disease, and a 2020 study in EBioMedicine highlighting a new treatment strategy using a nanovesicles-based system for neuronopathic Gaucher disease.
The ultimate goal of my research is to translate discoveries into effective therapies for treating Gaucher disease and other neurodegenerative diseases.
PhD: Pharmacology, University of Cincinnati, Cincinnati, OH, 1992.
Post doctoral fellow: Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1996.
Interests
Molecular pathogenesis and therapy of lysosomal storage diseases; glycosphingolipids metabolism; neurodegeneration.
Research Areas
Human Genetics
Publications
iPSC-derived neural precursor cells engineering GBA1 recovers acid β-glucosidase deficiency and diminishes α-synuclein and neuropathology. Molecular Therapy-Methods & Clinical Development. 2023; 29:185-201.
A brain penetrant progranulin-derived biologic protects against neuronopathic Gaucher disease. Molecular Genetics and Metabolism. 2023; 138:107367.
Earlier-onset, more severe neurodegeneration in PGRN KO mice with a decreased dose of D409V Gba1. Molecular Genetics and Metabolism. 2023; 138:107207.
PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases. Proceedings of the National Academy of Sciences of USA. 2023; 120:e2210442120.
Editorial: Neuronopathic lysosomal storage diseases - specific neuronal characteristics and therapeutic approaches. Frontiers in Molecular Neuroscience. 2022; 15:1078804.
Treatment of a genetic brain disease by CNS-wide microglia replacement. Science Translational Medicine. 2022; 14:eabl9945.
Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice. International Journal of Molecular Sciences. 2022; 23.
Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease. Journal of Molecular Medicine. 2021; 99:1639-1654.
Substrate Reduction Therapy Reverses Mitochondrial, mTOR, and Autophagy Alterations in a Cell Model of Gaucher Disease. Cells. 2021; 10.
Optimization of Eliglustat-Based Glucosylceramide Synthase Inhibitors as Substrate Reduction Therapy for Gaucher Disease Type 3. ACS Chemical Neuroscience. 2020; 11:3464-3473.
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