Lim, In Kyoung (임인경) MD., PhD.
Department of Biochemistry & Molecular Biology, Ajou University School of Medicine, San 5 Woncheon-Dong, Yeongtong-Gu, Suwon, Kyunggi-Do 443-721, Korea
Laboratory of Cellular Senescence and Carcinogenesis (LCSC)
The focus of my research is to understand molecular mechanisms of carcinogenesis and cellular senescence by tumor suppressor, TIS21/BTG2 gene, in the various cellular processes, such as cancer development, aging-related diseases, cell death, and differentiation by employing mouse model system as well as cell culture analyses. Cancer research is focused on the characterizing effects of tumor suppressor gene, TIS21/BTG2, during carcinogenic processes, and cellular senescence work is focused on the characterizing basic mechanisms regulating senescence associated p-Erk1/2 (SA-pErk1/2) and actin cytoskeleton proteins, which remodels the morphology of senescent cells.
TIS21 is an early growth response gene that was first isolated from mouse SW3T3 fibroblast after treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). TIS21 belongs to the antiproliferative gene family along with BTG1, BTG3, and Tob genes. Human homolog of TIS21, named, BTG2 (B cell translocation gene 2), was cloned from a cDNA library of human lymphoblastoid cells as a gene associated with DNA damage response. Expression of TIS21/BTG2 is responsive to the various DNA damaging agent such as UV, ionizing radiation, chemotherapeutic agents in addition to various growth factors and cytokines. Recently, TIS21 has been reported as a major effector of p53-dependent proliferation arrest in mouse and human fibroblasts and inhibitor of oncogenic Ras. In my laboratory, we proposed TIS21, for the first time, as a potential tumor suppressor in the thymic carcinoma and the hepatocellular carcinoma by employing SV40T antigen transgenic mouse and TIS21 knockout mouse model systems, respectively. Indeed, TIS21 inhibited cyclin E biosynthesis and cyclin B1 associated kinase activities, indicating its regulations of G1/S and G2/M phases of cell division cycle. Moreover, we also reported the effects of TIS21/BTG2 gene on the feedback regulation of cyclinB1 and FoxM1 transcription factor, the enhanced cell death via regulations of MnSOD induction and GSK3b activity in mitochondria, the enhanced degradation of c-Myc protein in response to all-trans-retinoic acid, and the inhibition of hematopoietic precursor cell proliferation in response to estradiol. The following diagram briefly explains what we have reported about the role of TIS21 in our laboratory.
On the other hand, we also reported universal markers of cellular senescence, such as G-actin accumulation in nuclei and cytoplasmic accumulation of SA-pErk1/2. In addition to that, we could report, for the first time, the significant accumulation of reactive oxygen species in the senescent cells by using FACS analysis.
Doctor of Medicine (M.D.) Yonsei University Medical College, Seoul Korea (1978)
Master of Science (M.Sc.) Yonsei University Graduate School, Seoul Korea (1980)
Doctor of Philosophy (Ph.D.) Yonsei University Graduate School, Seoul, Korea (1983)