Current Projects

  1. Investigate the therapeutic value of induced pluripotent stem cell derived neural progenitor cells on Parkinson’s disease by increasing lysosomal acid β-glucosidase.
  2. Study the role of Progranulin, a novel factor of acid β-glucosidase, and therapeutic potential for treatment of Gaucher disease.
  3. Exploit the mechanism and feasibility of a new nanovesicle-based therapeutic system to delivery of functional enzyme for correction of acid β-glucosidase deficiency in neuronopathic Gaucher disease.


Shibuya, Y; Kumar, KK; Mader, MM D; Yoo, Y; Ayala, LA; Zhou, M; Mohr, MA; Neumayer, G; Kumar, I; Yamamoto, R; et al. Treatment of a genetic brain disease by CNS-wide microglia replacement. Science Translational Medicine. 2022; 14.

Zhao, X; Hasan, S; Liou, B; Lin, Y; Sun, Y; Liu, C. Analysis of the Biomarkers for Neurodegenerative Diseases in Aged Progranulin Deficient Mice. International Journal of Molecular Sciences. 2022; 23.

Zhao, X; Liberti, R; Jian, J; Fu, W; Hettinghouse, A; Sun, Y; Liu, CJ. Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease. Journal of Molecular Medicine. 2021; 99:1639-1654.

Peng, Y; Liou, B; Lin, Y; Fannin, V; Zhang, W; Feldman, RA; Setchell, KD R; Grabowski, GA; Sun, Y. Substrate Reduction Therapy Reverses Mitochondrial, mTOR, and Autophagy Alterations in a Cell Model of Gaucher Disease. Cells. 2021; 10.

Wilson, MW; Shu, L; Hinkovska-Galcheva, V; Jin, Y; Rajeswaran, W; Abe, A; Zhao, T; Luo, R; Wang, L; Wen, B; et al. Optimization of Eliglustat-Based Glucosylceramide Synthase Inhibitors as Substrate Reduction Therapy for Gaucher Disease Type 3. ACS Chemical Neuroscience. 2020; 11:3464-3473.

Davis, HW; Vallabhapurapu, SD; Chu, Z; Wyder, MA; Greis, KD; Fannin, V; Sun, Y; Desai, PB; Pak, KY; Gray, BD; et al. Biotherapy of Brain Tumors with Phosphatidylserine-Targeted Radioiodinated SapC-DOPS Nanovesicles. Cells. 2020; 9.

Sun, Y; Liou, B; Chu, Z; Fannin, V; Blackwood, R; Peng, Y; Grabowski, GA; Davis, HW; Qi, X. Systemic enzyme delivery by blood-brain barrier-penetrating SapC-DOPS nanovesicles for treatment of neuronopathic Gaucher disease. EBioMedicine. 2020; 55.

Di Martino, S; Tardia, P; Cilibrasi, V; Caputo, S; Mazzonna, M; Russo, D; Penna, I; Realini, N; Margaroli, N; Migliore, M; et al. Lead Optimization of Benzoxazolone Carboxamides as Orally Bioavailable and CNS Penetrant Acid Ceramidase Inhibitors. Journal of Medicinal Chemistry. 2020; 63:3634-3664.

Miranda, CJ; Chisari, E; Northcott, N; Pandya, J; Liou, B; Fannin, V; Blackwood, R; Dane, A; Kia, A; Canavese, M; et al. One-off liver directed AAV gene therapy achieves long term uptake of acid beta-glucocerebrosidase by macrophages of affected tissues in Gaucher disease. Molecular Genetics and Metabolism. 2020; 129.

Zhao, X; Hettinghouse, A; Liou, B; Fannin, V; Blackwood, R; Liu, C; Sun, Y. The therapeutic effect of progranulin derived Pcgin on neuronopathic Gaucher disease. Molecular Genetics and Metabolism. 2020; 129:s165-s166.

Schiffer, V; Santiago-Mujika, E; Flunkert, S; Schmidt, S; Farcher, M; Loeffler, T; Schilcher, I; Posch, M; Neddens, J; Sun, Y; et al. Characterization of the visceral and neuronal phenotype of 4L/PS-NA mice modeling Gaucher disease. PLoS ONE. 2020; 15.

Liou, B; Zhang, W; Fannin, V; Quinn, B; Ran, H; Xu, K; Setchell, KD R; Witte, D; Grabowski, GA; Sun, Y. Combination of acid β-glucosidase mutation and Saposin C deficiency in mice reveals Gba1 mutation dependent and tissue-specific disease phenotype. Scientific Reports. 2019; 9.

Peng, Y; Liou, B; Inskeep, V; Blackwood, R; Mayhew, CN; Grabowski, GA; Sun, Y. Intravenous infusion of iPSC-derived neural precursor cells increases acid β-glucosidase function in the brain and lessens the neuronopathic phenotype in a mouse model of Gaucher disease. Human Molecular Genetics. 2019; 28:3406-3421.

Zhou, X; Paushter, DH; Pagan, MD; Kim, D; Santos, MN; Lieberman, RL; Overkleeft, HS; Sun, Y; Smolka, MB; Hu, F. Progranulin deficiency leads to reduced glucocerebrosidase activity. PLoS ONE. 2019; 14.

Chen, Y; Jian, J; Hettinghouse, A; Zhao, X; Setchell, KD R; Sun, Y; Liu, C. Progranulin associates with hexosaminidase A and ameliorates GM2 ganglioside accumulation and lysosomal storage in Tay-Sachs disease. Journal of Molecular Medicine. 2018; 96:1359-1373.

Jian, J; Chen, Y; Liberti, R; Fu, W; Hu, W; Saunders-Pullman, R; Pastores, GM; Chen, Y; Sun, Y; Grabowski, GA; et al. Chitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease. EBioMedicine. 2018; 28:251-260.

Sun, Y; Liou, B; Chu, Z; Inskeep, V; Blackwood, R; Peng, Y; Davis, HW; Qi, X. Systemic delivery of acid β-glucosidase by SapC-based nanovesicles for neuronopathic Gaucher disease therapy. Molecular Genetics and Metabolism. 2018; 123:s137-s138.

Fleming, SM; Santiago, NA; Mullin, EJ; Pamphile, S; Karkare, S; Lemkuhl, A; Ekhator, OR; Linn, SC; Holden, JG; Aga, DS; et al. The effect of manganese exposure in Atp13a2-deficient mice. NeuroToxicology. 2018; 64:256-266.


Research Team

Benjamin Liou 
Senior Research Assistant

Venette Inskeep
Research Assistant II

Yi Lin, PhD
Research Associate