Park Laboratory

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The overarching goal of our research programs is to understand how developmental signaling and stem cells are engaged in tissue homeostasis, regeneration, and cancer, and use that knowledge to develop biomarkers and therapy for human diseases. As model systems, we mainly utilize genetically engineered mice and organoids with a specific interest in Wnt signaling. 

 

Wnt signaling plays critical roles in governing various cellular processes during embryogenesis, organogenesis, and tissue homeostasis. Aberrant activation of Wnt signaling contributes to human diseases including cancer. However, given the crucial roles of Wnt signaling in tissue homeostasis and regeneration, direct targeting of Wnt signaling as a cancer treatment is still challenging. To overcome this, we have focused on identifying and investigating cancer-specific regulators of Wnt signaling. Employing comprehensive approaches including transcriptomics, genomics, and proteomics, we identified several candidate genes potentially modulating Wnt signaling specifically in cancer.

Our studies on several Wnt signaling regulators, including PAF (PCNA-associated factor)/KIAA0101/PCLAF, CRAD/KIAA1211/CRACD (Capping Protein Inhibiting Regulator of Actin Dynamics), TMEM9 (Transmembrane protein 9), and others also evolved into various research projects unveiling molecular and cellular targets for cancer therapy and tissue regeneration.

Cell Quiescence Exit in Tissue Regeneration and Cancer
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Stem and progenitor cells play crucial roles in tissue homeostasis and regeneration. However, it remains ambiguous how stem and progenitor cells undergo constitutive or conditional activation and division for tissue homeostasis and regeneration. PAF (PCNA-associated factor; KIAA0101/PCLAF) is specifically expressed in stem/progenitor cells and cancer cells and seems indispensable for mitogenic activation of the stem and progenitor cells. We investigate genetic, cellular, and molecular mechanisms of PAF-associated stem/progenitor cell activation during tissue regeneration and human disease, including cancer. 

CRAD Tumor Suppressor
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We recently discovered a new tumor suppressor gene called CRAD (Cancer-Related Regulator of Actin Dynamics; KIAA1211/CRACD). CRAD inhibits actin polymerization, and genetic and epigenetic inactivation of CRAD accelerates tumorigenesis (Jung et al., Nature Cell Biology). Based on the frequent loss of CRAD in cancer and Crad knock-out mouse phenotypes, we interrogate the pathological impacts of CRAD inactivation on cell plasticity and tumor initiation. 

Updates
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Hippo-activated telomerase-expressing cells in pancreatic regeneration

Photos updated (7/2021)

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Kyung-Pil received the National Research Foundation fellowship (6/2021).

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Welcome, Lana! (1/2021)

PAF Remodeled DREAM Complex quiescence KIAA0101 PCLAF

How Cells Bypass Quiescence in Cancer

Kim et al. "PAF Remodels the DREAM Complex to Bypass Cell Quiescence and Promote Lung Tumorigenesis"

Molecular Cell (accepted 1/2021)

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Welcome, KyungPil! (12/2020)

Targeting Wnt signaling in cancer

Targeting Wnt Signaling for Gastrointestinal Cancer Therapy: Present and Evolving Views (12/2020)

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Welcome, BongJun! (10/2020)

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Wnt blockers to ameliorate pain induced by chemotherapy (10/2020) 

R01 renewed (8/2020)

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Welcome, Shengzhe! (7/2020)

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2nd CPRIT Investigator-Initiated Research Award (2/2020)

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As a tenure-track Assistant Professor, Youn-Sang will run his own lab at Chung-Ang University, Seoul, Korea (starting 3/2020)

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Welcome, Yuanjian! (1/2020)

© Jae-Il Park Laboratory

MD Anderson Cancer Center