1. You recently published a paper, in the journal "PNAS, (2014)", titled "Inhibition of master transcription factors in pluripotent cells induces early stage differentiation".
- Can you please briefly summarize this paper?
Successful combination of induced pluripotent stem cells and efficient strategies for stem cells expansion and differentiation provide a new possibility in the field of regenerative medicine. Nevertheless, one of the most important bottlenecks in the field of regenerative medicine is low efficiency of commitment as well as complicacy entailing the process of commitment. Our report contributes to this ongoing endeavor in order to make stem cell differentiate to different lineages with high efficiency. Previous reports have established that stem cells are tightly regulated by the interplay of few transcription factors such as Oct4, Sox2 and Nanog which are termed as master transcription regulators of pluripotency. So we hypothesized if we could perturb the fine balance of these core transcription factors which are the main players in stemness state and thereby can modulate the initial phases of cell differentiation. To this end we employed of E. coli molecular chaperon Skp which is capable of physically interacting to Sox2 and subsequently showed that this interaction inhibits Sox2 and Oct4 transcriptional activity which in turn suppresses the stemness and initiate differentiation.
Our study has multiple important consequences. Most importantly this strategy of stem cell differentiation can be developed as a general strategy for the overall process of differentiation into particular cell types and thus may be supplemented known differentiation protocols. Our study provides an important message to understand the significance of time and balance of transcription factor expression for the differentiation. It is reported that a key to decide the cell fate is not the level of core transcription factors, Oct4, Sox2 and Nanog, individually, but their mutual balance.
Consequently it appears that blocking or depleting any one of these factors may not serve good to make the cells differentiate. It is therefore important to find ways to tweak with the overall balance of these factors to achieve any fruitful differentiation result. Taking together, our study has opened up new avenues to divulge the role of balance of various transcription factors which may hold the key for future aspects of stem cell engineering. Finally, our approach can also be extended to a therapeutic aspect. It has been a debate over last few years about the cancer stem cell hypothesis. The presence of a small population of stem cells in malignant tumors are believed to be capable of metastasize and give rise to a tumor of heterogeneous cell population, which is a similar process of organism development in recapitulation. So in order to treat cancer efficiently it is highly essential to get rid of this small population of cancer stem cells. Efforts have already been started to address this issue, and in parallel to this line of thinking our approach provides another way to tackle this problem. Yet the mode of this kind of heterologous protein therapy remains to be determined. But at least in principle our approach seems to work well to target this issue.
- Can you please tell us the main difficulties you had in the laboratory work and how you overcame them?
Basically my background was structural biology and bioinformatics with little knowledge in cell and molecular biology. So when we conceived this study I faced many predicaments due to little prior experience in this field. More over our labs core expertise also rested upon Structural Biology and Biophysics. So initially I landed upon many problems and issues regarding design and performing experiments relating stem cell biology. In this respect I enormously thank my professor Kyeong Kyu Kim who constantly supported me to transmutate my weakness to my strengths. He constantly encouraged me to learn more and to know the unknowns as this is the only philosophy to do science. He not only created new opportunities for me to venture in to the new field of study but also constantly monitored efficient planning to harvest the maximum.
I am also thankful enormously to Prof Jong-Sun Kang who put her diligent efforts to teach me various aspects of stemcell biology and without her help the pursuit of this study would have been extremely difficult. I would also like to extend my gratitude to Myong-Ho Jeong of stem cell biology lab who also actively contributed in the study and helped me immensely to give shape to this project.
Finally I am thankful to our School of Medicine which provided a highly conducive environment to share and discuss my research with people of truly interdisciplinary experiences. Moreover, all sorts of facilities and amenities provided by our school and Samsung Biomedical Research Institute have actually facilitated immeasurably in pursuing this study.
2. Please introduce your laboratory, university or organization to bio-researchers in Korea.
Our lab is primarily a structural biology lab which lately achieved fame by elucidating the structural mechanism of how the junction of B-DNA and Z-DNA is formed. As a structural biology lab our lab has primarily invested to decipher the mysteries underlying complex biological processes by looking in to the atomic structures of proteins which are involved in the process. But recently we have taken a more holistic approach to study these biological processes. To us it's the question we want to address is of utmost importance and thereby we utilize several interdisciplinary approaches to address the problem. In this regard we are not restricted to only structural studies. We are now involved in studies relating to other broad fields starting from stem cell biology, ubiquitome, microbial host-pathogen interaction, so on and so forth. Hence apart from studying and learning one's own field, the holistic exposure to various other fields of study appears immensely helpful to me.
So in our lab, one can hone his or her skills to become an independent researcher of his or her own rights.
3. Please tell us your experiences and your thoughts related to research activities in Korea.
Korea is one of the world's biggest growing economies. As the great Indian poet and Nobel laureate Rabindranath Tagore had aptly described Korea as the "Lamp bearer of the East", I think Korea is having enormous potential and illuminating future in the direction of science and technology. The honest and diligent approach towards study and the very fabric of Korean society to value the importance of education and knowledge has given it a huge impetuous to develop a conducive environment for research and development. Lately it has become one of the important contributors to high impact journals in various fields of science and technology which is a gauge to appreciate the rapid growth in all aspects.
4. Please tell us your difficulties and good memories as foreign researcher in Korea
The main difficulty as faced by many foreign researchers is the language. I have felt in many instances that even important scientific meetings and conferences are sometimes conducted in Korean and thus it becomes extremely difficult to follow and appreciate cutting edge researches in many cases. One more difficulty that I faced is while choosing subjects for course work for my graduate subjects. I have seen that some very interesting courses are offered in Korean and thus prevented foreign students to opt for those courses. I think Korea and most importantly our school is working to resolve this issue and I am hopeful that in near future this problem will be solved.
Most of the good memories of mine pertain to the wonderful Korean people I met as collogue and friends. Their kind and ever helpful attitude touched me and comforted me in those days when I felt home sick. Additionally, I have received enormous amount of help and support in my research activities from my peers and I always cherish them as important assets of my life.
5. Can you provide some advice for younger foreign scientists who have plans to study in Korea?
As economic crunch has crippled the possibilities of scientific funding in USA and Europe, Korea offers an excellent venue of parallel aptitude to opt research goals and fulfillment of career dreams to the global scientific community. Korean government and many private enterprises are investing generously in the fields of research and development. Hence I think if somebody is diligent and want to pursue his or her research career, Korea provides a land of unrestricted opportunities. I strongly believe one will be highly satisfied with the overall temperaments and efforts that are being put in to achieve scientific excellence.
6. Future plan?
I would like to continue study in the field of Science and technology and contribute to the ongoing endeavor. To this end I wish to continue studies and researcher throughout.
7. Do you have anything else that you would like to tell Korean scientists and students?
I don't know whether I am capable enough to advice, since I am still in the phase of learning and will continue to learn throughout my life. But instead I can share my likings. I have always tried to pursue whatever I love doing. Hence I think success depends of passion and craze. If one enjoys whatever he or she does then work transmutates to worship and one's effort becomes offerings to mankind. So if my advice is meaningful to anyone, I would urge them to love and get attached to whatever they do.