An Engineering-Approach and Lung Organoids and Understanding Lung Regeneration

Qi Tan, Ph.D., Postdoctoral Fellow, Tissue Repair and Mechanobiology Laboratory, Mayo Clinic
Qi Tan, PhD

Dr. Qi Tan obtained his PhD from the Chinese University of Hong Kong. He is currently a postdoctoral research fellow at Mayo Clinic in Rochester, Minnesota in the US. His research focuses on genetically engineering the self-organization of fibroblasts into alveolar lung organoids using lineage transcription factors, as well as implantation of organoids derived from multiple cell sources, including induced pluripotent stem cells, to support functional tissue integration and regeneration.

The Scientist

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 don’t have a particular scientific idol that influenced my scientific path; however, I can list a few names I respect, including Craig Venter, Shinya Yamanaka and Feng Zhang.

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 don’t like hypothesis-driven research and 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.

The Science

Please describe the focus of your current research.

My research has two primary foci: firstly, lung fibrosis not only induces fibroblast/myofibroblast proliferation, extracellular matrix (ECM) deposition and tissue remodeling, but also inhibits epithelial regeneration, which leads to a progressive decline in lung function. Regenerative therapies for fibrosis should not only aim to inhibit fibroblast/myofibroblast proliferation and ECM deposition, but also promote the differentiation of alveolar epithelial cells when the mechanical microenvironment is altered. I am working on genetically engineering the self-organization of fibroblasts into alveolar lung organoids using lineage transcription factors. I am also testing the effect(s) of epigenetic modulators to alleviate fibrosis and promote lung regeneration in an organoid model, as well as the effect of reprogramming efficacy. Secondly, I study implantation of organoids derived from a variety of cell sources, including induced pluripotent stem cells (iPSC), to support functional tissue integration and regeneration which will provide a substantial step forward in cell therapeutic approaches for chronic respiratory disease.

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 and the recellularization of decellularized lung are both important advances in lung research.

What breakthroughs would you anticipate in the next five years?

It is very difficult to predict; however, I would guess that we might see genome editing in lung differentiation 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 differentiation and organogenesis. Organoid techniques allow us to investigate challenging questions; for example, how do stem cells become lineage-specific type I and II pulmonary cells, and how does alveolar structuring form in vitro?

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.

The Tools

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.