Application of organoid technology in the identification and characterization of prostate luminal progenitor subsets and their ability to serve as the cell-of-origin for prostate cancer
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Historically, prostate luminal epithelial progenitors and cancer cells were difficult to culture, thus hampering the generation of representative models for prostate stem cell and cancer research. In the early 2010s, we have invented a prostate organoid culture methodology that favours the growth of prostate luminal epithelial cells, and can efficiently maintain prostate luminal epithelial progenitors and cancer cells as organoids. In this presentation, I will first describe the development of this prostate organoid technology, and how we have successfully used it for the identification of prostate stem cells or progenitor subsets and the generation of novel prostate tumor models for drug discovery and assessments. Moreover, I will also talk about our recent unpublished works on the elucidation of the ability of different prostate luminal progenitor subsets to serve as the cell-of-origin for immune-evading prostate cancer using integrated organoid technology, single cell transcriptomic analyses and in vivo grafting approach. Lastly, I will end my presentation by discussing the key challenges in the current state of prostate organoid technology.
Dr. Chee Wai Chua (蔡志偉) is a Principal Investigator, Professor and PhD mentor at the Shanghai Cancer Institute, a Group Leader at the State Key Laboratory of Systems Medicine for Cancer, and an Adjunct Professor at the Department of Urology, Shanghai Jiao Tong University School of Medicine-affiliated Renji Hospital. He has been selected for the Shanghai Overseas High Level Talent Program, and appointed as a Professor of Special Appointment, which carries the title “Eastern Scholar” by Shanghai Institutions of Higher Learning. Prior to relocating to Shanghai, Dr. Chua has developed a novel organoid culture method that can maintain prostate luminal progenitors, prostate and bladder cancers as well as metastases. Notably, these works were published in top journals and earned him two international patents. In the first ever held organoid workshop at Cold Spring Harbor Laboratory, Dr. Chua has served as a Laboratory Instructor to teach the invented prostate organoid culture methodology to trainees from all over the world. He is currently an Editorial Board Member for the Cancer Letters journal, and has initiated and served as a Guest Editor for the Special Issues on “Prostate Cancer” and “Stem Cells and Cancer”. He has also previously served as an eLife Community Ambassador to help promoting equal learning opportunity to early career researchers from developing nations. In particular, he has helped training Malaysian scientists with his roles as an International Collaborative Partner of Universiti Tunku Abdul Rahman (UTAR)’s Global Research Network, an Adjunct Professor of UTAR and Taylor’s University Malaysia as well as a Visiting Research Scientist of Universiti Kebangsaan Malaysia. Since the inception of his lab in Shanghai, Dr. Chua has actively involved in various stem cell and organoid-related research and scholarly activities in China, including serving as the Co-Chair of the Organizing Committee of International Conference on Frontiers in Stem Cell and Cancer Research for three consecutive conferences held in 2019, 2021 and 2024, respectively, invited as a speaker in various major organoid and prostate cancer conferences nationally and internationally, providing expert opinion for setting up the standardized human normal and malignant intestinal organoid protocols as well as involved in drafting the consensus on clinical application of organoid models in drug sensitivity evaluation for precision cancer treatment. Currently, Dr. Chua’s research group focuses on the identification of different prostate luminal stem cell and progenitor subsets, and systematic characterization of their ability to serve the cell-of-origin for immune-evading androgen receptor-independent prostate cancer subtypes. In addition, the Chua’s group has also actively pursued the goals of optimizing the invented organoid technology for improved human tumor organoid derivation rate as well as establishing mouse models that can recapitulate the multi-step process involved in human prostate cancer bone metastasis.