Diana Dou, is the 2015 winner of the ISEH New Investigator Award, given to the best presentation by a PhD student. Diana is a PhD candidate in the Molecular Biology Interdepartmental Doctoral Program at the University of California, Los Angeles. She did her undergraduate degree at the California Institute of Technology, receiving a Bachelor of Science with Honors (2010); Majors: Biology/ Business, Economics, and Management (BEM), Minor: English. She has been working in the field of hematology and stem cells for 4 years and her areas of expertise are lncRNAs, HOXA genes and HSC development. She joined ISEH 4 years ago.
Diana kindly participated in a Q&A session with Connections. Below she talks about her experience as a graduate student, her current projects, her excitement about science and research, and shares with us her secret for a balanced life.
Tell us about your graduate education. About the experience of being a graduate student.
Being a graduate student requires a lot of patience, determination, and optimism. It’s the first time where success and progress aren’t guaranteed, no matter how much I work and study. But, it’s also the most exciting—like when an experiment proves a hypothesis right and the pieces to the puzzle start to add up and make sense. I don’t know if anyone can really educate a graduate student other than to just throw one into lab and make him/her ask questions and try to figure out how to answer them until it just becomes natural. Reading papers is important, but that’s just background, like packing supplies before an expedition. The real experience comes from going out there, doing the experiments, optimizing those experiments, and letting the data take you on an adventure. Some days, it’s frustrating, some days, it’s exhilarating, but it’s never boring.
Who has most influenced you to become a scientist, and how did they influence you?
I love magic shows, but when I was a kid, no one would ever tell me how the tricks work. In fourth grade, our science teacher did this experiment called Elephant’s toothpaste and, with just a little dish soap and hydrogen peroxide, this huge green tube started foaming out of the beaker, like magic, but he answered all of my questions on how and why it worked and I was able to do the same “trick” by myself. A couple of years later, the same teacher assigned us a “Science Giants” project to present on famous researchers and I loved learning Rachel Carson’s story so much that I looked up everyone else’s assigned “Giants”, too. Learning about what they achieved in their lives was truly inspiring and I was impressed at how scientists got to design their own greatest adventures.
How did you find your way to the hematology and stem cells scientific field?
Well, I wanted to organize a stem cell panel when I was an undergrad at Caltech so I went to ask David Baltimore for advice. He not only agreed to be the moderator, he also insisted we invite Hanna Mikkola, who studies HSCs at nearby UCLA, as the academic voice on the panel. When I got to UCLA for graduate school, I went to listen to two of her post-doc fellows present on their very exciting projects. One of those projects was on the inability of hESC-derived HSPCs to self-renew and I e-mailed Hanna that afternoon to ask if I could rotate with her. Fortunately, she remembered me and I got my foot in the door.
What is the overall aim of your research?
The overall aim of my research project is to elucidate the involvement of the medial HOXA genes to human HSC self-renewal. I hope to establish the downstream targets of individual HOXA genes contributing to HSC self-renewal, determine the mechanisms involved in the induction of HOXA cluster expression, and assess the effects of inducing HOXA genes on HSC function to determine the extent to which HOXA genes impact HSC self-renewal. In the process, I hope to identify other pathways in addition to the HOXA genes that are important for inducing and maintaining human HSC self-renewal.
Tell us a little about the subject of your presentation.
My talk focused on the requirement of the medial HOXA gene expression in human HSC self-renewal. Our lab developed a two-step differentiation protocol that generates immunophenotypic HSCs from ESCs that can differentiate into multiple hematopoietic lineages and express adult beta-globin, but are unable to self-renew and engraft. From microarray analyses comparing HSPCs isolated from different stages of development, we identified the medial HOXA cluster genes as critical for HSPC self-renewal and find they are not present at the correct levels in ESC-derived HSPCs. We also showed that RA signaling is required as a key inducer of HOXA gene expression in the hemogenic endothelium and is defective in ESC-derived HSPCs. In summary, in the context of the developmental timeline, we were able to generate cells of the definitive HSPC lineage from pluripotent stem cells and identify two molecular barriers limiting their ability to self-renew.
What is the most exciting or intriguing result you’ve gotten so far?
I think the most intriguing result is that retinoic acid signaling can induce the HOXA cluster genes in hESC-derived hematopoietic cells, but it cannot maintain this expression once the treatment is removed. This is intriguing because, while it is a success in some regards, there is still something missing, which I hypothesize involves lncRNAs. Personally, that’s exciting because my other main project is with lncRNAs of the HOXA cluster. In addition, applying retinoic acid at different stages of development induces different HOXA genes. These results just reveal again how elegantly structured and complex these tightly regulated signals occur in development.
What's the biggest challenge you've ever faced in your research?
Every time I do an experiment for the first time, it’s automatically the most frustrating and difficult challenge I’ve ever faced in research up until the second I optimize it and actually get reliable results. So, my current biggest challenge is getting the 5’ RACE to work in the region I suspect lncRNA(s) involved in human HOXA regulation is located… Other than that, deciding what to do next is always hard—there are always so many options I wish I could do them all!
How do you balance between work and personal life?
Since many of my friends are also in research, those two aspects sometimes intersect. Of course, a 50-50 balance can never be achieved, because work is never truly finished in this career, as that would mean that every question in the universe has been successfully and definitively answered. To overcome this quandary of “never enough time” and maintain a personal life, I sleep much less than is recommended. It’s all about cost vs. value—and I am willing to sacrifice a few hours of sleep each night to pursue my research and make sure I have some fun outside of lab too.
What are you working on most intensely right now?
I’m working most intensely on understanding the best statistical tests to use on the data we’re putting in our paper right now. It’s confusing, but necessary, and consulting with a statistician really helps. Many scientists overlook the importance of statistics, but if we are to impart any significance on the results we collect, it is as critical to understand when and why a certain statistical test is used and its strengths and weaknesses as it is to understand the experiment itself. To do otherwise would be both unethical and misrepresent the data.
There are a lot of interesting aspects of this scientific field; what do you find the most exciting?
The possibilities right now are endless because the technology is finally catching up to what we want to do. From high-throughput sequencing that allows a whole genome view of RNA/DNA expression, histone marks, and accessibility, to CRISPR/Cas9 allowing us to neatly delete or insert a gene so specifically opens infinite doors from addressing basic molecular biology questions about how a gene fits into a pathway to the correction of diseases through gene therapy. It’s thrilling to see that what used to be theoretical is actually going into clinical trials (i.e., SCID) and know that’s just the beginning. Picking one is just impossible because tomorrow has finally become today.
In your field, what do you hope we will know in five or 10 years that we don’t know now?
The main reason our field exists is to help people, so, of course, I hope we figure out how to generate engraftable human HSCs in vitro so that anyone who needs a bone marrow transplant can get one. I hope we understand HSC development so well that we are able to provide a map that can pinpoint where individual mutations occur in every patient afflicted with a blood-based disease.
Who is your most influential senior investigator mentor and how did he or she help you?
The most influential scientific mentor for me is Scott E. Fraser who was my undergraduate academic advisor at Caltech and still is a solid supporter even now that he is Provost at USC and I am a graduate student at UCLA. Scott is awesome. In my first quarter of college, we had a chat where I casually mentioned an interest in research. Before I left, he’d e-mailed five other professors and even offered me a stint in his own lab. Great mentors are able to see something in their students that they cannot see themselves and are able to give those students the confidence and training to outperform their own expectations. That is certainly true for Scott, who always nudged me to aim for more than I thought I could do and never told me I couldn’t do something, which is how I ended up graduating from Caltech with two majors and a minor while working in a lab, playing two NCAA sports, and organizing speaker events. To this day, he still takes time to respond to my e-mails when I have questions about imaging, which experts to consult, and career advice. I credit him for always believing in me and for making me believe in myself, and for encouraging me to find all of science, particularly the difficult questions, interesting. Most importantly, Scott helped me become fearless.
What are your future career plans?
I plan to continue in academic research. I haven’t decided on what field or lab I want to do post-doc training in because there are so many interesting topics, including, but not limited to lncRNAs, gut microbiota, and, of course stem cells of all types. I hope to have a lab of my own and start a company on the side so that what I find in the lab can reach outside the world of academics and everyone—including politicians—will see how important basic science research is.
What general advice would you give a young person considering a career in science?
Never stop asking questions and being amazed and don’t limit that curiosity only to your field of research. There’s no such thing as irrelevant if it inspires you or simply makes you marvel at how cool it is. It’s supposed to be fun, always. Even if experiments are not working, always go in with the optimism that the next one will work.
What are the results of a scientific career that makes it worthwhile and exciting?
Everyone wants to change the world at some point in his/her life. Scientists do that every day by adding a bit of knowledge, lighting up a little bit of the dark frontiers with each question and experiment and finding. Even if the average person may never wonder how or why they breathe, bleed, grow, and live, those questions and answers are still universally relevant. Everything we do is so new that no one else has done it before and, when we get a bit of data that answers a question that affects everybody, in that moment of discovery the scientist is the only one in the entire world of billions who knows a secret fact of our universe.
How were you introduced to ISEH?
My PhD thesis advisor, Hanna Mikkola, is a long-time member. She brought me to ISEH 2012 right after I joined her lab so I could get a chance to present my research and also interact with the field of hematology.
What do you find most valuable about ISEH?
The best thing about ISEH is the small size that allows the meetings to be focused and members to easily network. There’s not only a true interest in developing young investigators’ careers, but the ability to actually act on that interest and further the advancement of students.
Why do you attend the ISEH Annual Scientific Meeting?
It’s the best place to get very focused and relevant feedback on my research. The professors are all easily approachable and seem more relaxed in this smaller meeting than others. Plus, the meeting is always held in a really cool city.
What is your favorite ISEH Annual Scientific Meeting memory?
I always like it when there’s dancing, especially if the DJ’s good. That’s the best part: seeing stiff PIs shed their coats and dignities to break it down.
What are your hobbies?
I play basketball, fence sabre, and run half-marathons regularly. I also like to follow the stock market, experiment with different recipes, and read non-biology articles when I can.
What are your favorite books?
A Farewell to Arms (Ernest Hemingway), The Nonexistent Knight (Italo Calvino), The Name of the Wind (Patrick Rothfuss)
What are your favorite movies?
Return of the Jedi, The Devil Wears Prada
If you could meet one person (dead or alive) who would it be and why?
This is a no-brainer. I would meet Pat Head Summitt, the Coach Emeritus of the University of Tennessee’s Women’s Basketball Team. She is not only the winningest coach in college basketball—men’s or women’s—she is also a pioneer, great mentor, and a true inspiration as a person. I had the fortune of growing up watching Coach Summitt’s teams dominate college basketball. At the time, I didn’t know anything about Title IX, or appreciate the significance of the `96 “Year of Woman” Olympics that came right in the middle of her three-peat championships, I just knew that the intimidating coach with orange blazers and laser eyes always came up with winning plays, her players were awesome and I wanted to be one of them. Even though science became a bigger draw and I was never that good at basketball, I continued to love watching the Lady Volunteers play and I did end up playing for the Caltech Women’s Basketball team. Even after her diagnosis and forced retirement with early onset Alzheimer’s in 2012, she continues to be the face of women’s basketball and has, as usual, conducted herself with superhuman courage and perseverance. Without Pat Summitt, girls in sports—and, indeed, confident girls ready to take on or over the world—would be much more of a rarity and I would certainly not be the person I am today.