One area of Dr. Chiang's research has been focused on studies of Cbl family proteins and their functions in T cell development and activation by using mouse genetic approaches. Three Cbl members have been identified as c-Cbl (Cbl), Cbl-b and Cbl-3 (Cbl-c) in mammalian cells. Cbl proteins consist of multiple functional domains, including an N-terminal tyrosine-kinase binding (TKB) domain, a ring finger (RF), a proline-rich region (PRO), and a C-terminal leucine-zipper/UBA domain. They interact with multiple protein molecules to influence signaling events via their protein-protein interaction domains. Cbl and Cbl-b proteins have been found to be critical factors in negatively mediating TCR signaling, which he is interested in. Dr. Chiang is also interested in the roles of telomeres in cancer and aging biology. Telomeres are structures at the end of eukaryotic chromosomes, consisting of hexanucleotide repeats and associated proteins, which play a critical role in cellular senescence, apoptosis and tumorigenesis. Telomere length is maintained by telomerase and telomere-associated proteins. Telomerase consists of two essential components, telomerase RNA template (TR), which encodes the template for telomere synthesis, and telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase. A number of telomeric associated proteins have been identified, including telomeric repeat binding factors 1 and 2 (TRF1 and TRF2), TRF1-interacting protein 2 (TIN2), tankyrase 1 and 2, protein interacting with NIMA-interacting factor 1 (PINX1), Rap1 and POT1. To understand the mechanism of maintenance of telomere length, Dr. Chiang has generated several mutant mouse lines related to telomerase, telomere-associated proteins with mouse knockout and transgenic technology.