Zejin Sun, MD, PhD
Assistant Research Professor
Primary Appointment: Department of Pediatrics
- PhD:Indiana University School of Medicine, Indianapolis, IN
- MS:Beijing Medical University, Beijing, China
- MD:Tianjin Medical University, Tianjin, China
Current Research Interests:
To understand and evaluate the role of Cyclin dependent kinase inhibitor 3 (CDKN3) in tumorigenesis. Cdkn3 is a dual-specificity cell cycle regulatory phosphatase. In interphase, CDKN3 prevents premature G1/S transition by dephosphorylating interphase cyclin-dependent kinases (CDKs) to prevent premature inactivation of the RB pathway. During cell division, CDKN3 dephosphorylates the key mitotic kinase CDK1 at threonine-161 to extinguish CDK1 activity at the exit from mitosis. CDKN3 knockdown in cultured cells impairs the spindle assembly checkpoint (SAC), accelerates cell cycle progression and causes chromosomal instability, suggesting that it may function as a tumor suppressor. However, since CDKN3 has been reported as overexpressed in some malignancies and mutated or silenced in others, it is unclear whether it functions as an oncogene or a tumor suppressor.
Therefore, our lab is focused on the role of CDKN3 in the carcinogenesis. We developed the first Cdkn3 conditional knockout mouse model. We found the increased DNA synthesis and proliferation, impaired mitosis evidenced by increased frequency of micro- and multi- nucleation, aneuploidy, and accumulation of supernumerary centrosomes in Cdkn3-/- cells. Long-term observation of Cdkn3-/- mice revealed an increased risk of death from a variety of hematopoietic (leukemia and lymphoma) and non-hematopoietic (lung, prostate and ovarian) malignancies. These findings establish Cdkn3 as an in vivo tumor suppressor in bone marrow and a variety of other tissues. In the long term, Cdkn3 mice will serve as a tool to dissect the function of this phosphatase in cell cycle control in more detail, and may prove useful in preclinical studies of chemotherapy of CDK-hyperactive, genomically unstable leukemia and lymphoma.
Address: 1044 West Walnut Street, R4-414, Indianapolis, IN 46202