The Research Achievements of Assistant Professor Po-Nien Tsao Made the Cover of the Top Journal of Development

Development—the international top journal of Developmental Biology, used NTU Assistant Professor Po-Nien Tsao's research findings as its over in the latest issue (June 5, 2009), and published Professor Tsao's research achievements.

The study of stem cells and regenerative medicine has become fads of late.  Actually, development biology and regenerative medicine are the two sides of the same coin.  In order to practice regenerative medicine, one must first understand the development process of an organ, and it normally takes more than manipulating some stem cells to get the job done properly.

Lung diseases are quite common, including bronchopulmonary dysplasia for premature infants, infections (tuberculosis, influenza, SARS, etc.), lung cancer and chronic pulmonary obstructive diseases, etc.  Understanding the development process of the lung lays a foundation for the treatment of the various lung diseases simply because to truly understand an organ, one must first understand its development process, just like to understand a car, one must understand the process by which a car is manufactured.

Professor Po-Nien Tsao is a physician at the Department of Pediatrics of National Taiwan University Hospital.  Specializing in the study of lung development while pursuing a doctorate degree in the Institute of Clinical Medicine of NTU under the tutelage of Professor Fon-Jou Hsieh, Professor Tsao was able to create the placenta growth factor - transgenic mice to discover the new mechanism for the induction of emphysema. His paper on that topic was published in the top journal of Respiratory Medicine "The American Journal of Respiratory and Critical Care Medicine."

Capitalizing on a grant provided by the National Health Research Institute, Dr. Tsao went to the Pulmonary Center of Boston University School of Medicine to study under Dr. Wellington Cardoso for two years. In the first year, he learned the foregut in vitro organ culture system. In the process of learning, he had to first understand the structure of a mouse embryo, then learned how to dissect a mouse embryo to obtain its foregut, followed by learning to create an in vitro environment to facilitate the growth of foreguts, and learning to identify the organs cultivated through in vitro method such as lungs, stomach, pancreas, livers, etc. In addition, he learned to cultivate in vitro embryonic lungs, and how to remove the complete embryonic lungs (11-12 days of pregnancy) and observe the phenomenon of branching during 2-3 days in vitro. In this whole learning process, Dr. Tsao utilized the above mentioned technique to complete his first thesis on how the Notch signaling controlled the differentiation of the developing airway epithelial cells. His thesis was published in the "Journal of Biological Chemistry."

Subsequently, Dr. Tsao made use of a tissue specific Shh-Cre mouse to successfully create a lung epithelial specific Pofut1 knockout mice, which is a conditional gene knockout mice that removes all Notch signaling in the lung epithelial cells. The purpose of his creation was to study the function of Notch signaling and their importance to the lungs in vivo. Interestingly enough, Dr. Tsao discovered that the Pofut1 gene knockout mice could all survive at birth, and there were no respiratory symptoms found. However, within one month after birth these mice displayed a high mortality rate. Dr. Tsao analyzed the lung tissues of these mice and discovered that the Pofut1 mice tended to lose their normal respiratory epithelial tissues gradually after birth and the said tissues were replaced by a number of squamous epithelial cells, a phenomenon very similar to the respiratory epithelial lesion found in asthma or chronic obstructive pulmonary diseases. Dr. Tsao took one step further to analyze the lung epithelial cells of the Pofut1 mice and discovered that in the respiratory tracts no secretive cells (the so called Clara cells) can be found from the mice's fetal period to the adult period, and that the Clara cells were replaced by the ciliated cells and the overly grown neuroendocrine cells which covered the entire respiratory tract.

At the same time, this particular type of lung performance can be found in vitro mice culture system and another type of lung epithelial cell specific Notch component - Rbpjk gene knockout mice. This interesting finding allows us to understand that, in the developmental process of the lung, Notch signaling is used to control the respiratory ciliated cells and to balance the secretion of the epithelial cells. Owing to this meritorious achievement, the latest issue of the "Development" journal chose Dr. Tsao's research findings as its cover and published Dr. Tsao's research efforts in great depth.

Additionally, in view of the importance of developmental biology, NTU's College of Medicine recently engaged our alumnus Dr. Cheng-Ming Chuong (graduated in 1978) as a chair professor to take charge of the developmental biology and regeneration disciplines of our university. Dr. Chuong worked at the Department of Pathology, School of Medicine of University of Southern California for many years. Over the last decade he devoted himself quietly to the study of ectodermal layer of birds' (including feathers, scales and hair), and extended his research from the bird feathers to the evolution of archaeopteryx fossils. Up to this date he has had four theses published in the "Nature" journal, and he was elected fellow of Academia Sinica in 2008 in one fell swoop.

Dr. Chuong is currently collaborating with Dr. Sung-Jan Lin, a dermatologist at NTU Hospital's Department of Dermatology. By working together, the two eminent scholars intend to extend their basic research to the regeneration of the human hair. Dr. Lin won Academia Sinica's Young Scholar Research Writing Award for 2008 not too long ago. Dr. Choung is very concerned about the development of developmental biology and regenerative science at NTU. Since 1998 he has worked closely with Professor Fon-Jou Hsieh to spearhead the development of developmental biology in Taiwan and consistently provided assistance to other researchers. With Dr. Choung taking the lead, and providing guidance to the young generation of outstanding researchers such as Dr. Tsao and Dr. Lin, NTU can certainly expect a bright future in the years to come in the area of developmental biology and regenerative science.