Dr. Li's research has been focusing on chromosome biology. Chromosomes are large DNA molecules carrying hereditary elements called genes, which control development and behaviors of living organisms. Eukaryotic chromosomes are linear, and each molecule has two termini called telomeres.
Although telomeres do not contain any genes, they help to maintain genome stability and prevent tumorigenesis. On the other hand, cancer cells need telomeres to ensure their unlimited proliferative ability. Hence, disruption of telomere maintenance has also been suggested in cancer therapy. Because telomeres in normal human somatic cells shorten with each round of cell division, these cells cannot proliferate forever. They stop growing (senescence) when telomeres are too short. Therefore, telomere length-dependent senescence is an important cellular aging mechanism. In several organisms, telomeres form a heterochromatic structure that can suppress the expression of genes located nearby (at subtelomeric regions).
Microbial organisms that cause diseases in humans usually have different relative abilities to damage hosts (virulence). Interestingly, in quite a few microbial pathogens, genes encoding surface antigens that are essential for pathogen virulence are located at subtelomeric regions, suggesting that telomeres play an important role in the regulation of expression of these genes.
Dr. Li's lab is interested in studying telomere functions in Trypanosoma brucei, a protozoan parasite of southern Africa causing sleeping sickness in humans and Nagana in cattle. She has identified one essential protein that binds to T. brucei telomere DNA directly and found that this protein is critical for the telomere terminal structure. The VSG genes in T. brucei encode surface antigens that are crucial for its survival in mammalian hosts. Only one VSG gene is expressed at a time, exclusively from one of ~20 subtelomeric loci. Recently, Dr. Li has identified a telomeric protein that plays an important role in the regulation of subtelomeric VSG gene expression. Additional telomeric proteins have also been identified in T. brucei and their functions are currently under investigation. These studies will be helpful for understanding the pathogenesis of T. brucei and the general functions of telomeres.