A mini introduction from my manuscript Revised

Hello All as you

Hello all as you probably came acrossed my workshop post regarding a small segment from the introduction of my manuscript, and many of you provided great suggestions and comments to make it clearer so here I post up the revised section here for you to see the changes afterwards. The reviewers thought the writing was clear and easy to follow, thanks guys!

Introduction
An effective treatment regimen for hematologic disease and malignancy has been challenging due to a lack of suitably-matched donors (1). To circumvent this issue, efforts have focused on generating hematopoietic stem and progenitor cells (HSPCs) from embryonic stem (ES) (2, 3) and induced pluripotent (iPS) cells (4, 5). However, the wide-spread application of pluripotent stem cells is currently hampered by their tumorigenic potential. A proposed alternative is the direct conversion of fibroblasts into HSPCs and blood cells (6, 7). Although lineage specification and reconstitution potential are currently inefficient (6, 7), evidence suggests that improvements in direct hematopoietic reprogramming could provide a viable strategy for hematopoietic based therapeutics. Aided by GFP reporters, recent studies demonstrated that overexpression of specific transcription factors facilitated generation of neurons and cardiomyocytes from fibroblasts (8, 9), suggesting the conversion of fibroblasts into functional HSPCs was plausible. These studies highlight the importance of having a reporter system for hematopoietic marking and a method to track cellular reprogramming.
Since the blood cell therapy field lacks a reliable reporter for hematopoietic production after differentiation of ES and iPS cells (5, 10), the development of a hematopoietic restricted marking system is essential. Furthermore, a fluorescent reporter system enables real time tracking of full reprogramming (11, 12), permits the study of reprogramming intermediates (13, 14), and may facilitate the eventual use of small molecules for direct reprogramming, as demonstrated recently for iPS cell derivation (15). Additionally, a reporter construct could aid in the purification and removal of undifferentiated pluripotent cells to minimize teratoma formation upon transplantation.
An effective reporter should be inactive in fibroblasts and pluripotent stem cells, but turned on in the desired reprogrammed cell fate. Transcription factors such as Gata2, Hoxb4 and Evi1 were previously employed as reporters due to their essential roles in HSPC genesis, maintenance and/or amplification (16-20). However these reporters were not limited to blood cell lineages, and this limited their utility (21, 22). Additionally, these transgenes used in the production of reporter mice (23) cannot be virally introduced into hematopoietic reconstituting cells because the reporter is too large for the viral backbone (24).

A mini introduction from my manuscript (also part of my thesis dissertation)

INTRODUCTION

The development of a hematopoietic restricted marking system is essential since the blood cell therapy field is currently lacking a reporter, a reporter that can faithfully readout hematopoietic production following  embryonic stem(ES) and induced pluripotent stem (iPS) cells based differentiation (1, 2). Additionally, this reagent is especially useful for efforts aimed at developing an efficient protocol for the direct reprogramming of fibroblasts into hematopoietic stem and progenitor cells (HSPCs). As cell transplantation, an effective treatment for hematologic disease and malignancy for decades (3), remains challenging due to a lack of suitably-matched donors.  Recent efforts focus on generating HSPCs from ES cells (4, 5) and iPS cells (2, 6).  The wide-spread application of pluripotent stem cells is currently hampered by the tumorigenic potential of undifferentiated pluripotent stem cells. A proposed alternative is the direct conversion of fibroblasts into HSPCs and blood cells (7, 8); However, lineage specification was inefficient (8) and multilineage reconstitution was not as robust (7). Current evidence suggests improvements in direct hematopoietic reprogramming could be a viable strategy for cell therapy.  Overexpression of various transcription factors generated functional neurons, and cardiomyocytes from fibroblasts (9, 10).Not only these studies showed that fibroblasts can de-differentiate to another cell type, but showed that GFP reporter was an effective tool. Thus, regardless whether the study calls for pluripotent cells or fibroblasts to generate HSPC, a reliable hematopoietic marker is beneficial. Having a fluorescent reporter system enables real time tracking of full reprogramming (11, 12), allows reprogramming intermediates to be studied (13, 14), and can facilitate the eventual use of small molecules for direct reprogramming, as demonstrated recently for iPS cell derivation (15). Additionally, the reporter can aids in the purification of differentiated cells from the undifferentiated ones to minimize teratoma formation upon transplantation.

Writing in your life

Today’s blog is not directly related our class assignment but I thought it’s an interesting experience to share about writing. Last weekend I attended a Catholic engage encounter retreat in Cedar Falls. We need to take this class in order to get married as Catholics. The whole weekend was memorable, but most of all was how much writing involved. It was vigorous!

We arrived at the American martyr retreat house at 7:00pm to check in at 7:30pm. After registration and settled in our rooms, one single room for each sex, the bell rang to signal us the retreat session had begun. All engaged couples headed toward the conference room to listen about the itinerary. The first day will be finding ourselves, second day will be finding each other, and third day was finding god. Thus we listened to lectures about ourselves. The part that I found interesting was after each lecture we were sent to our room to write down our answers based on a list of questions in the allotted time. My initial thoughts was that this feels like I am grounded so I had to go to my room to do homework. It took a while to jot down some notes since I wanted to formulate my thoughts better. When the time was up, the bell rang again to allow our significant other to come into our room to exchange our writings. We had to read each other writing twice, one was for our head and the other was for our heart. Again, it was a bit odd at first since we usually talk about things and rarely ever do we communicate about issues through writing. Looking at his writing at first I couldn’t help to pick out one grammatical error, but then when I read it over again I was able to understood the words, his penmanship and how these brought me back to the day when he handed me a tiny piece of paper with a poem he had carefully crafted for me. Oh I miss the good old days …. We exchanged several session like this on Friday night. We felt even closer than we already are.

The next morning we were woken up to the song ‘Hakuna Matata” from the Lion King at 6:40AM J, after getting ready we attended mass and ate breakfast. Afterwards we headed to the conference room, then we started series of lectures and silent writings. After the first few writing, I felt more and naturally as I used to keep a journal. In complete silence between the brick walls I wrote crazily and un-prohibited especially in the place of worth ship I let go of all disguise and masks and expectations. Writing was much much more productive, and I like the fact of just using paper and pen to write. This routine ended at 10pm at night…so that was lots of writing.

This experience was quite interesting to me in many ways. First, in our ever increasing demand for technology society (which I love) but this place required none – I felt like I am decades before in this place. There were no computers, no fancy class room except for prayer rooms, very peaceful and serene. Most of all I missed writing and reading letters using pen and papers. Since when has anyone really write a letter to someone in actual ink anymore. Importantly, no matter how far we advance as a human race, writing is still a core to our communication. I felt that through writing I can expressed complicated emotions more clearly that I would have a hard time explaining verbally. Writing allowed us to be more mindful and more effective as listener rather than talking. This form of communication is important and it’s required in every aspect at times when verbal communications fail. So I thought the writing out strategy the leaders used in the retreat was great to get other couples talking about difficult stuffs that they weren’t be able to communicate verbally.I found this especially true I used writing to express my feelings to my parents that I had hard times saying face to face to them.So the old ways not always the bad way J. 

An interview with Professor X on the topic of writing

 

Two weeks ago I had the pleasure to interview Professor X on the topic of writing. Professor X is an extremely busy faculty with an enormous publication record. He is the director and co-directors of multiple programs/departments, and an advisor of graduate students on top of running his own research lab. Yet he juggles them all pretty efficiently, thus this is one of the reasons I chose to interview him as I could learn a thing or two on how to be successful on this road we called academia.

Besides his ability to juggle many things at once, Professor X is quite personable. Unlike the examples mentioned in class regarding some awkward responses from the faculty that students got during their interviews, Professor X was very open, honest, and energetic. He welcomed my questions as he anticipated the next. The conversation just flowed from one question to the next with ease. To recap, I opened my interview with Professor X by asking him what is his takes on writing. I was surprised and impressed at his honestly when he said “it’s the hardest thing to do – psychologically and emotionally…” He elaborated that it is a difficult task to overcome all the barriers to do it. However, once he’s in the zone he can write for hours without a break; it is “as rewarding as reading a book.” I can totally relate to this. I often found myself staring at the blank page for a while to find the perfect word/phrase to start the paragraph. But once the light goes off on the top of my head, I would type away. Just like how I would stayed up late to finished chapters of a book.

Professor X further suggested that to prevent being ‘stuck’ or ‘to get the feeling in the mood’ is just to write whatever that comes to mind then correct them later, and never cite while you write. The latter advice was new to me, but professor X explained that doing so will help keep the ideas flowing without any interference since looking up the references and inserting them –the process itself can be distracting from the stream of thoughts; once he’s finished for the part then he will go back and look at places where references are needed. I found this idea to be very useful. In the past, I rarely write without citing, I will put [ref here] before continue on the next sentence; but I couldn’t help to feel like if I don’t insert the reference then and there I might miss it later on. Also, the idea of turning in a draft with “[ref here]” still is not quite so exciting. However, I have been practicing what Professor X told me, and it is hard at first because my left brain will tell me to go find those references to insert but my right brain tells me otherwise. I have resisted the urge to insert references or googling to find information. I am beginning to like this strategy as I am able to write more with less distraction (sometimes in the past I would look up references and ended up reading them for few hours).

Next, I asked whether Professor X found writing enjoyable and if he writes more professionally or leisurely. He enjoyed writing especially once he’s in the zone, and most of his writing are academics. He shared that at this stage of his career (full professorship) he allowed himself to be more creative in writing such as writing a review. When he first started out as an assistant professor, he had to write more “academia”, more science, and more technical to establish his career. However, as he became more established he showed his creativity in writing a review paper. This prompted me to ask my next question about his writing habits. Professor X has several modes of writing, but most of which consist of weekly writing. When he’s in the zone then he writes daily, 2-3hrs periods without breaks. However, when he’s out of it or procrastinating, he will “struggle to do it weekly” he smiled as he talks about this (I think this is something we all can relate to). He write best early in the morning, the first thing he does when he gets up is to write as “morning hours have gold in mouth” [this is when our brain is at its freshest and clearest]. I guess I do kind of similar thing although it is after my morning workout and the commute to lab. But when I would arrive at lab with everything quiet and peaceful. I would turn on my computer and write for 2hrs daily. I felt my mind is quite sharp then, and after accomplishing my writing goal I felt quite productive for the rest of the day.

Finally, I wrapped up our interviewed with a question on his secret to stay motived or productive in writing and whether he has any advice for writing well. He said is to keep the TV off, start early, and be consistent…minimize all the distractions. Another useful advice I take away from our conversation was that “quit on a good note” not down beat. Whenever he found himself stuck he would work on a different paragraph, or take a little break, but never quit, then come back and start on a different page. The ideas will eventually come back to us, and when we end in a positive note we will be more motivated to write for the next session.

As Professor X had said writing is tough process, and as we all know it takes a lot of hard work, disciplines, and motivations. However, writing can be enjoyable especially after we master the art of it. I think with hard work and dedication we all can be as successful as Professor X, Professor Y or Z in our department one day, and who knows next time around it might be us giving advice to our young students on the the art of writing.  I am glad to have the opportunity to meet up with Professor X as I have learned some valuable tips from him.