An Engineering-Approach and Lung Organoids and Understanding Lung Regeneration
Dr. Qi Tan obtained his PhD from the Chinese University of Hong Kong. He is now an Assistant Professor of Biomedical Engineering at Mayo Clinic in Rochester, Minnesota in the US, where he also completed a postdoctoral research fellowship. His research focuses on delineating cellular and transcriptional mechanisms of how epithelial cells maintain lung epithelial-mesenchymal homeostasis and protect lung from fibrosis, with a specific focus on CEBPA regulating epithelial identities and their paracrine effects, and to alleviate lung fibrosis via restoring CEBPA expression in vivo with CRISPR activation. The long-term goal of his research program is to develop bioengineering methods including CRISPR gene activation, epigenetics drugs and cellular products to promote pulmonary tissue regeneration and repair.
(Last updated on November 9, 2020)
What inspired you to pursue scientific research?
I have been an enthusiastic believer that technology and science will make human life better since I was a child, and I also enjoy performing experiments and solving problems.
Do you have a scientific idol that influenced the scientific path you’ve chosen?
I will not say I have any particular scientific idol, but my postdoc mentor, Dr.Tschumperlin, influenced my scientific path the most and helped me develop my current research programs and independence.
What led you to studies in your current field?
After my undergraduate studies I discovered the allure of biomedical research is modification of biological phenotype relative to human disease by using genetic engineering and tissue engineering, which led me to my current field. I prefer to work like an engineer: identify a problem, find the tools, then solve the problem.
What hobbies do you have outside of the lab?
I like travelling, hiking, PC games, watching movies, cooking. I also occasionally play soccer, table-tennis and board games with friends.
Please describe the focus of your current research.
My current research seeks to delineate the homeostatic and fibrosis-resolving roles of anti-fibrotic factor CEBPA in lung epithelial cells and to develop a new regenerative therapeutic strategy to treat lung fibrosis in experimental murine models using non-genome editing CRISPR gene activation to promote fibrosis resolution and restore epithelial-mesenchymal homeostasis. Here are my current research programs and potential future research directions:
- To delineate the role of CEBPA/BMP signaling from epithelial cells in maintaining lung epithelial mesenchymal homeostasis and its protective role or fibrosis-resolving effects in pulmonary fibrosis.
- Development of a gene activation platform (In vitro and In vivo) with CRISPR activation system and epigenetics drugs.
- Discovering new regulators maintaining homeostatic and fibrosis-resolving signaling.
- Development and optimization of in vitro lung cell culture models including 3D culture model and organoid model, and in vivo fibrosis models including aging mice and conditional knockout mice model.
These research ideas align with my long-term goal that help me understand homeostasis in the lung and integrate cell biology, immunology, epigenetic, genomics and gene editing technology to promote tissue repair in lung fibrosis.
What do you consider to be the most important advance(s) in lung (regenerative) research in the last five years?
I think iPSC lung lineage differentiation, recellularization of decellularized lung, lineage tracing studies are great advances in lung research.
What breakthroughs would you anticipate in the next five years?
It is very difficult to say; however, I would like to see the progress on how genetic engineering changes lung generation within the next five years.
What has the adoption of organoid cultures added to your research? What types of biological questions has this technique enabled you to probe?
Traditional 2D cell culture has its limitations. As well, type I and type II alveolar cells are very difficult to culture, with an unfavorable microenvironment for studying lung regeneration and organogenesis. Organoid techniques allow us to investigate challenging questions; for example, how do stem cells/progenitors become lineage-specific type I and II pulmonary cells, and how do epithelial cells and mesenchymal cells interact with each other.
What impact do you see organoids having on the lung field? What technical hurdles remain before this can be realised?
The use of organoid platforms has led to advancements in in vitro organogenesis and disease modeling, and subsequently, it has created exciting possibilities for the development of innovative new therapies. However, precise control of lung differentiation and branching morphogenesis of stem cells still remains a challenge for us.
Have you tried PneumaCult Medium for organoid (bronchosphere) culture and how did it work?
I have tried PneumaCult-Ex Medium for bronchial epithelial cell culture on the plastic culture dish, but I have not had the opportunity to try it in organoid culture.
- Liu W et al. (2019) Targeted regulation of fibroblast state by CRISPR-mediated CEBPA expression. Respir Res 20(1):281.
- Tan Q et al. (2018) Epigenome editing enters the arena. A new tool to reveal (and reverse?) pathologic gene regulation. Am J Respir Crit Care Med 198(5):549-51.
- Tan Q et al. (2019) Nascent lung organoids reveal epithelium- and BMP-mediated suppression of fibroblast activation. Am J Respir Cell Mol Biol 61(5): 607-19.
- Haak AJ et al. (2019) Selective YAP/TAZ inhibition in fibroblasts via dopamine receptor D1 agonism reverses fibrosis. Sci Transl Med 11(516).
- Tan Q et al. (2017) Human airway organoid engineering as a step toward lung regeneration and disease modeling. Biomaterials 113: 118–32.
- Tan Q et al. (2013) In vivo identity of tendon stem cells and the roles of stem cells in tendon healing. Stem Cells Dev 22(23): 3128–40.
- Ni M et al. (2013) Engineered scaffold-free tendon tissue produced by tendon-derived stem cells. Biomaterials 34(8): 2024–37.
- Tan Q et al. (2012) Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering. Tissue Eng Part A 18(7–8): 840–51.
- Tan Q et al. (2012) Effect of in vitro passaging on the stem cell-related properties of tendon-derived stem cells-implications in tissue engineering. Stem Cells Dev 21(5): 790–800.
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Qi Tan, PhD