Through the studies of the catabolism of glycoconjugates, Drs. Li have contributed substantially to the basic understanding of the biochemical basis of Fabry's disease and Tay-Sachs disease. Their laboratory was the first to correctly establish the structure of the glycosphingolipid that accumulates in the kidney of patients with Fabry's disease [J. Biol. Chem. (1971) 246: 3769]. In 1973, they discovered that the catabolism of Tay-Sachs ganglioside (GM2) requires a protein cofactor in addition to the enzyme (beta-hexosaminidase A) [J. Biol. Chem. (1973) 248: 7512]. Subsequently, type AB Tay-Sachs disease was established to be the deficiency of this protein cofactor. They have successfully cloned the gene and overexpressed this gene in E. coli to produce the recombinant activator protein [J. Biol. Chem. (1994) 269: 16276]. The crystal structure of this activator protein was solved in collaboration with Dr. C. S. Wright of the University of Virginia.

Drs. Li have also found that the catabolism of GM2 in man is different from that of mouse [J. Biol. Chem. (1998) 273: 66]. Their results provided an explanation on why the Hex A-knock out mice (the murine model for type B Tay-Sachs disease) does not resemble the disease in man. They have also deciphered the nucleotide sequence of the activator protein gene that is responsible for expressing the different specificity of the protein cofactors in man and mouse [J. Biol. Chem. (1999) 274: 28612]. Their work has been continuously supported by the NIH since 1971.