1. Can you please briefly summarize the paper?

Transcription factor EB (TFEB), a member of the MiT/TFE family of basic helix-loop-helix leucine zipper transcription factors, is a well established central regulator of the autophagy/lysosomal-to-nucleus signaling pathway. Our group under the guidance of Prof. Jho Eek Hoon had recently published 2 significant papers about the novel roles of TFEB in CDDpress journals - Cell Death and Differentiation and Cell Death & Disease. In particular, the paper published in Cell Death & Disease, where I am the first author, was selected as ‘’CDDpress: Our Monthly Top Picks’’. Not long ago, we had also successfully published an exhaustive and comprehensive review of TFEB in Cell Death and Differentiation (IF; 15.8). In my personal humble opinion, our findings on TFEB represents a breakthrough in TFEB field as we challenged the long standing dogma of TFEB as a regulator of autophagy/lysosomal biogenesis.

To commemorate the 30th anniversary of TFEB since its first discovery, we have decided to write a comprehensive review paper entitled ‘’Past, Present, and Future Perspectives of Transcription Factor EB (TFEB): Mechanisms of regulation and association with disease’’, which was successfully published in Cell Death & Differentiation. I personally feel that a comprehensive review paper that discusses the future direction of TFEB is essential as it open up new research areas.

In our review article, we analyze the past, present, and future perspectives of TFEB throughout the previous 30 years and provide thorough insights. There are six sections to this extensive review paper ranging from TFEB evolution, its massive involvement in signaling pathways and diseases and TFEB role in the centrality and dynamics of lysosomes. We also discussed the recently discovered autophagy-lysosomal-independent role of TFEB and its future prospects as an appealing therapeutic target in modulating health and disease.

Our review article particularly focuses on the major advances of TFEB during the last 30 years. We also provide a timeline on the major findings of TFEB. Molecular mechanisms of TFEB regulation encompassing its cytoplasmic and shuttling as well as its pathophysiological roles in human diseases such as neurodegenerative diseases, lysosomal storage disorders, cancers, metabolic disorders and aging were also discussed. We substantially updated recently uncovered important topics involving the role of TFEB in the centrality and dynamics of lysosomes. Not to mention, we also outline all of TFEB's recently discovered moonlighting functionalities. This review paper contains 7 main figures, 3 tables and 1 supplemental information file

Overall, I believe that this in-depth review study contributes to our understanding of TFEB as a key molecular player. Its elucidation will indeed take us one step closer to transforming TFEB from basic research into clinical and regenerative applications.

I strongly recommend anyone who is interested in TFEB, to give a try reading this informative review paper. I am sure that it will be beneficial to new readers and it may sparks new idea too. I encourage the readers to read the supplemental information too.

2. Can you please tell us the main difficulties you had in the laboratory work and how you overcame them?

It has been a roller coaster ride to get this review paper published in Cell Death and Differentiation (CDD). A span of almost 1 year was spent from writing/drafting the review paper to submission which includes revision and being finally accepted by CDD. Since this is not a commissioned nor we were invited to write this review paper, I planned and drafted the manuscript very carefully, taking into consideration on how we could actually impress the editor of CDD. After a few rounds of discussion, we have decided to write a comprehensive review paper which covers the past, present and future perspectives of TFEB, with a little injection of our own personal thoughts. We tried our best to include all of the major breakthrough findings on TFEB in the past 30 years into this review paper which consists of around 150 references. We spent around 5 months to complete the whole manuscript.

With god’s grace, our review paper was sent for peer review by CDD editor, and we finally got the reviewers’ comment after 2 months of anxious waiting. Three reviewers were assigned for this review paper and all of them had given good appraisal for this review paper. However, there was a bit shortcoming in this review paper, that has to be fixed and a total of almost 25 comments were given. Some of the questions were quite tough to answer.

I am currently working as a senior researcher in ILIAS Biologics, an exosome-based pharmaceutical company. During the revision period, I spent two to three hours every day after work to revise the manuscript considering that I have to work during day time. It was mentally exhausting as I have to manage my time between work and at the same time being devoted in writing the rebuttal for the revised manuscript. I spent most of my weekends answering all of the reviewer comments and occasionally had phone calls with Prasad to discuss the answers. Knowing how to spend my time wisely and prioritize how I want to spend my time is necessary for productive outcome. Time management is about managing and executing choices. After 3 to 4 months of revision, we managed to complete the rebuttal under the guidance of Prof. Jho. Our review paper was finally accepted by CDD. It was a big relief and a good learning process for me. I learned a lot while preparing for this review paper. Perseverance, time management and critical thinking are definitely the key to success. Always believe in yourself and try to do your best and let god do the rest. I definitely felt a sense of accomplishment and I would like to take this opportunity to thank all the authors. A big shout out to Prof. Jho too for his hard work.

3. Please introduce your laboratory, university or organization to bio-researchers in Korea.

I graduated with a Ph.D degree from University of Seoul (서울시립대), under the supervision of Prof Jho Eek-Hoon. I joined Cell Signaling Transduction Laboratory (CSTL) back in September 2015 right after completing my Master’s degree from the National University of Malaysia. CSTL is quite a huge lab with around 7 to 8 PhD candidates and 2-3 Master postgraduates. I was quite amazed by how my advisor manage to handle so many students simultaneously. Our laboratory focuses on elucidating the underlying mechanisms of both Wnt and Hippo signaling pathways, in the search of discovering therapeutic targets of diseases caused by abnormal regulation of these pathways. Our lab is one of the longest standing and reputed lab which works on Wnt and Hippo signaling in Korea. We had published good research articles throughout the years which had gain a lot of recognition not only domestically but also internationally by the Wnt community. I am proud to be a part of CSTL.

To those who are new or have never heard of Wnt and Hippo pathways, these signaling pathways were first identified as essential regulator that contribute to cancer development, embryonic development as well as mechanism regulating organ size. They are also implicated in apoptosis, NF-κB signaling, synaptogenesis, embryonic stem cell maintenance/differentiation, as well as CNS diseases, making them of the most important signaling pathways that are being studied with the utmost attention around the world.

I am currently employed as a senior researcher in an exosome-based pharmaceutical company, ILIAS Biologics. ILIAS is one of the most promising start-up company in Korea and was the first Korean company who received approval by the Human Research Ethics Committee (HREC) in Australia to initiate Phase 1, the first-in-human trial of ILB-202, to treat cardiac surgery-associated acute kidney injury. So what do we actually do here? We specialize in developing engineered exosomes by loading large therapeutic payloads inside exosomes via our proprietary platform technology, EXPLOR®. By harnessing the power of our engineered exosomes, we opt to deliver therapeutic proteins to the undruggable intracellular pathways to treat life-threatening and hard-to-treat diseases. For those who are interested to be part of our journey, including foreigners who are seeking for job opportunity in Korea, please do not hesitate to drop us an email (https://www.iliasbio.com).

4. Please tell us your experiences and your thoughts related to research activities abroad.

I still remember vividly the day I sent an email to my beloved PhD advisor, Dr. Jho Eek Hoon, asking for his permission to join his laboratory back in 2014. I officially joined his lab in August 2015 right after completing my Master’s degree from the National University of Malaysia. In a blink of an eye, 7 years had passed. It was a brave and daunting decision, but I still stand by my decision till this day and I have not regretted every moment of it. In fact, it was one of the best memories I had in my life. Life has been very tough during my stay in Korea but that’s what makes me a more rounded and independent person.

During my PhD course, I was trained intensively physically and mentally. I was exposed to various kind of experimental techniques including CRISPR/Cas9 system, which is an essential in this new era genetic engineering. I also gained a lot of opportunities to participate in domestic and international conference and as well as meeting famous professor in the Wnt field. Life in Korea is not just about doing science, but it also gives you the chance to come out of your shell and unleash your hidden capabilities, which is crucial in instilling self-development. I had the chance to meet a lot of people with different backgrounds and try to assimilate their culture. Back in Malaysia, I never had such great opportunities. With limited lab facilities, I never had the chance to really do good research.

5. Can you provide some advice for younger scientists who have plans to study abroad?

To any foreigner who plans to study abroad, I strongly encourage you to take that brave step and it may be your life changing moment. However, my bit piece of advice is that, please find a good and caring advisor, someone who can really shape and transform you into a good scientist, someone who show mutual respect and trust, and someone who motivates you to do good science. I am glad that I have found one in Korea, which is Prof. Jho Eek Hoon, who acts like a father figure to me ㅋㅋㅋ (p/s: prof, just in case if you see this, please buy expensive food for me XD ㅋㅋ).
Go for your dream, go all the way but don’t take the wrong way.

6. Future plan?

Earn big money and make good publications?ㅋㅋㅋ

7. Do you have anything else that you would like to tell Korean scientists and students?

Erm, thank you for being considerate and bearing with the foreigners ㅋㅋ. I always think that people met for a reason and it’s called fate. Science is about learning and exploring together regardless of nationality. Thank you to everyone who has guided me along my life.