Cancer Immunology, Inflammation and Tolerance Program
Associate Professor of Biochemistry and Molecular Biology
Georgia Cancer Center
1410 Laney Walker Blvd., CN 2176
My laboratory research is focused on a novel form of biochemical modification of proteins, namely the Ufmylation pathway. We are interested in elucidating its biological functions, investigating its molecular mechanisms and exploring its potential roles in the pathogenesis and treatment of various human diseases including cancer.
The Ufm1 conjugation system:
The Ufm1 (Ubiquitin-fold modifier 1) conjugation system is a novel ubiquitin (Ub)-like system that consists of Ufm1-specific E1 enzyme (Uba5), E2 enzyme (Ufc1), and E3 ligase(s). Similar to other Ub-like systems such as SUMO, the Ufm1 system promotes ufmylation (covalent modification by Ufm1) of target proteins through a series of enzymatic reactions catalyzed by E1, E2 and E3. However, very few targets have been identified so far. Multiple lines of evidence indicate its involvement in the pathogenesis of various human diseases, including neurological disorders, hematopoietic diseases, diabetes, ischemic heart injury, atherosclerosis and cancer. Interestingly, several bi-allelic mutations of Uba5 genes have been identified to be linked to early-onset encephalopathy and recessive cerebellar ataxia. Ufbp1, a component of Ufm1 E3 ligase, was also identified as a new genetic risk locus in Parkinson’s disease, but its biological function remains poorly understood.
Ufl1/Ufbp1 protein complex: a Ufm1-specific E3 ligase
We have identified a novel protein complex including Ufl1 (Ufm1 ligase 1, also known as RCAD, NLBP, Maxer and KIAA0776), Ufbp1 (Ufm1 binding protein 1, also designated as DDRGK1, Dashurin and C20orf116) that was subsequently identified as a putative Ufm1 E3 ligase. In an attempt to elucidate the biological functions of these proteins, we have recently created knockout mouse models of Ufl1 and Ufbp1 and demonstrated that both Ufl1 and Ufbp1 are essential for embryonic development and hematopoiesis. We are currently investigating its role in intestinal homeostasis and blood cell development, respectively. In collaboration with other MCG laboratories, we are also interested in its role in heart development and the immune system.