Park Laboratory
Stem Cells and Cancer
We are studying stem cells and cancer using genetically engineered mouse models and organoids with a specific interest in Wnt signaling. Wnt signaling plays key roles in governing various cellular processes during embryogenesis, organogenesis, and tissue homeostasis. We are exploring how Wnt signaling controls tissue stem and progenitor cells and orchestrates tissue regeneration. Aberrant activation of Wnt signaling contributes to cancer. Given the crucial roles of Wnt signaling in tissue homeostasis and regeneration, direct targeting of Wnt signaling as a cancer treatment is challenging. To overcome this, we are in the study of new molecules, cancer-specific regulators of Wnt signaling, in a pre-clinical setting.
Updates
Biyun Zheng served as a hostess for the National competition of Digestive Elite (Shenzhen, China) and won the '2nd Prize of National Intestinal Disease Case Speech Competition' and the 'Best Popularity Award' (Peking, China; 11/2019)
Youn-Sang Jung received AACR-KCA Young Investigator Award (Nov 2019).
Moon Jong Kim received the ROSI seed grant (Aug 2019). 'Radiation-induced esophagitis and regeneration'
Youn-Sang Jung was nominated as the Anne Eastland Spears Fellow in GI Cancer Research (May 2019). 'Mechanism of diffuse-type gastric cancer initiation'
Youn-Sang Jung received the AACR Gastric Cancer Research - Debbie's DREAM foundation Fellowship
(April 2019).
CRAD, a new tumor suppressor in mucinous colorectal cancer
Mucinous colorectal cancer is highly metastatic and therapeutically resistant. We identified a new tumor suppressor gene encoding CRAD (cancer-specific regulator of actin dynamics). We found that genetic mutations or transcriptional downregulation of CRAD initiates the development of mucinous colorectal cancer.
Youn-Sang Jung et al., Nature Cell Biology 20, 1303-1314, 11/2018, News & Views
Targeting proton pump for colorectal cancer treatment
We found a new oncogene, TMEM9 (transmembrane protein 9), as an amplifier of Wnt/beta-catenin signaling. TMEM9 facilitates the assembly of v-ATPase (vacuolar proton pump), leading to the activation of Wnt signaling. Importantly, molecular targeting of TMEM9-v-ATPase suppresses colorectal cancer.
Youn-Sang Jung et al., Nature Cell Biology 20:1421-1433, 12/2018
A shared path to two destinations: PAF-Myc axis in tissue regeneration and cancer
Upon tissue injury, stem and progenitor cells exponentially repopulate for tissue repair. It was assumed that many signaling pathways might play critical roles in both normal tissue regeneration and tumorigenesis. We found that regenerating and cancer cells specifically express PAF (PCNA-associated factor). Importantly, PAF is required for expansion of self-renewing cells during intestinal regeneration and tumorigenesis, unveiling a pivotal signaling axis in both tissue repair and cancer.
Visualizing and manipulating self-renewing cells: Tert, a catalytic subunit of telomerase, is specifically expressed in self-renewing cells. We engineered mice to visualize and genetically manipulate Tert-expressing self-renewing cells. We found that Tert+ cells are quiescent stem cells conditionally activated by Wnt2/beta-catenin signaling for tissue regeneration.
© 2017 by Jae-Il Park Laboratory
MD Anderson Cancer Center