Kang-Yell Choi

In 1995, Kang-Yell Choi returned to South Korea and joined Yonsei University as a professor. He has served as chief of the National Research Laboratory for Molecular Complex Control and currently directs the Translational Research Center for Protein Function Control (TRCP), a program supported by the National Research Foundation of Korea and the Ministry of Science and ICT. He also founded CK Regeon Inc., a biotechnology company focused on developing therapies for conditions such as non-alcoholic steatohepatitis (NASH), hair loss, and diabetic wounds, which are associated with impaired Wnt/β-catenin signaling caused by CXXC5 overexpression.^[3]

Choi’s work has examined the regulation of Ras stability through the Wnt/β-catenin signaling pathway. His research identified that degradation of Ras, particularly K-Ras, occurs via GSK3-mediated phosphorylation followed by ubiquitin-dependent proteasomal degradation through recruitment of the β-TrCP E3 ligase. He further showed that oncogenic K-Ras can be stabilized by the loss of APC, leading to reactivation of Wnt/β-catenin signaling and the promotion of cancer stem cell activity and liver metastasis in colorectal cancer. These findings highlighted the potential benefit of inhibiting both Wnt/β-catenin and Ras–ERK pathways in cancer therapy. Choi later identified small molecules that promote degradation of β-catenin and Ras, which were found to inhibit the growth of colorectal and other cancers with activated Wnt/β-catenin and EGFR–Ras signaling.

Choi also identified CXXC5 as a negative feedback regulator of the Wnt/β-catenin pathway that interacts with Dishevelled (Dvl) in the cytoplasm. He found that CXXC5 is overexpressed in bald scalp tissue, diabetic wounds, and aged skin. His group developed PTD-DBM, a peptide that restores Wnt/β-catenin signaling by blocking the interaction between CXXC5 and Dvl. Topical application of PTD-DBM, particularly in combination with a Wnt/β-catenin activator such as valproic acid, was shown to promote hair growth and accelerate wound healing.

PTD-DBM was also observed to increase collagen production, support cell migration, and reduce reactive oxygen species and apoptosis in skin cells, indicating potential anti-aging effects. It has been used as a treatment agent for hair loss in various applications. Choi’s ongoing research includes the development of small molecules that mimic PTD-DBM activity through an in vitro screening system targeting the CXXC5–Dvl interaction, with several candidates showing promise for promoting hair regeneration, wound healing, and skin rejuvenation.

• 5-FU promotes stemness ofcolorectal cancer via p53-mediated WNT/β-catenin pathway activation. Nature Communications. (2020)^[4]
• WDR76 is a RAS binding protein that functions as a tumor suppressor via RAS degradation. Nature Communications. (2019)^[5]
• β-Catenin-RAS interaction serves as molecular switch for RAS degradation via GSK3β. EMBO Reports. (2018)^[6]
• Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis. Journal of Investigative Dermatology. (2017)^[7]
• Small molecule binding of the Axin-RGS domain promotes β-catenin and Ras degradation. Nature Chemical Biology. (2016)^[8]
• Small molecule inhibitors of Dishevelled-CXXC5 interaction are new drug candidates for bone anabolic osteoporosis therapy. EMBO Molecular Medicine. (2016)^[9]
• The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing. Journal of Experimental Medicine. (2015)^[10]
• CXXC5 is a negative-feedback regulator of the Wnt/β-catenin pathway involved in osteoblast differentiation. Cell Death and Differentiation. (2015)^[11]
• Oncogenic K-Ras Accelerates Cancer Stem Cell Activation via Aberrant Wnt/beta-catenin Signaling. JNCI-Journal of the National Cancer Institute. (2014)^[12]
• Ras Stabilization via Aberrant Activation of Wnt/b-catenin Signaling Promotes Intestinal Tumorigenesis. Science Signaling. (2012)^[13]
• MEK1/2 Inhibitors, AS703026 and AZD6244, may be potential therapies for K-ras Mutated Colorectal Cancer that Is resistant to EGFR Monoclonal Antibody Therapy. Cancer Research. (2011)^[14]
• Wnt5a Is Required for Endothelial Differentiation of Embryonic Stem Cells and Vascularization via Pathways Involving Both Wnt/β-Catenin and Protein Kinase Cα. Circulation Research. (2009)^[15]
• Ste5 thether multiple protein kinase in the MAP kinase cascade required for mating in Saccharomyces cerevisiae. Cell. (1994)^[2]
• Crystal structure of LacI member RurR, bound to DNA: Minor groove binding by α helices. Science. (1994)^[1]