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MCB’s Linda Geng honored at the 2012 Weintraub Awards Symposium

Jun 2012 | Michelle 714 Comments

Linda Geng and her dog Sesame

Someday, when we defend our theses, we’ll heave a big sigh of relief, drink a little too much champagne, and turn our attention to future endeavors (whatever they may be). For most of us, what comes next probably doesn’t include more school.

Though she’s finished her PhD, recent MCB grad Linda Geng isn’t done yet: she’s going to be a double doctor.

For Geng, an MD/PhD student, graduating from MCB meant diving right back into the medical side of the Medical Scientist Training Program. MSTP students complete their first two years of medical school, then do their PhD, and then return to the final two years of MD training. After defending her PhD last December, Geng transitioned from the lab to the clinic, starting with a rotation in pediatrics. Suddenly, she was working with humans instead of cultured cells, trying to recall details she’d memorized in classes several years prior. She’s taken it all in stride, though, welcoming the challenges her training brings.

Last month, Geng was able to come back as a basic scientist for a day. She was honored as one of thirteen students nationwide to receive a Harold M. Weintraub Graduate Student Award, which is given to senior PhD students or recent grads for innovative research in biological science.

At the Weintraub Symposium on May 4, Geng presented her work on the role of the transcription factor DUX4 in fascioscapulohumeral dystrophy (FSHD). A common genetic feature of patients with FSHD is a contraction of a repetitive region of the genome whose repeats each contain a copy of the DUX4 gene. Although DUX4 has long been considered a candidate causal factor in FSHD, the levels of DUX4 transcript in FSHD muscle were nearly undetectable. Along with other members of Stephen Tapscott’s lab, Geng tackled the challenge of unveiling the mechanism through which DUX4 is involved in FSHD.

In the following interview, Geng shares her thoughts about her science, grad school, and the perspective she’s gained as an MSTP trainee. The MCB Transcript congratulates Linda on her award and wishes her well in the future!

MCB Transcript: Your work centers around DUX4, a gene previously hypothesized to be involved in FSHD. First off, what is FSHD?  What is DUX4?

Linda Geng: Facioscapulohumeral dystrophy, or FSHD, is the third most common muscular dystrophy and is characterized by progressive degeneration of selective skeletal muscle groups. It is a debilitating disease and is estimated to affect 1 in 20,000 people. DUX4 is a double homeobox gene whose coding sequence was first identified to be contained within the genomic locus that is thought to be responsible for FSHD. It is a transcription factor that is toxic when ectopically expressed in muscle cells, but very little is known about its function and activity.

MCBT: You found that even though it’s expressed at low levels in diseased muscle, DUX4 seems to have major effects. Was this surprising? What was the most surprising/interesting result for you?

LG: It was always puzzling why DUX4 was so hard to detect in FSHD muscle cells. How can something of such low abundance cause a dominant disease? When we discovered that its expression is actually at a relatively high level is a subset of cells at any given point in time, we were surprised but also amazed at how everything was starting to make sense. We believe that this shows a snapshot and that over time, every cell will eventually express a burst of DUX4 sufficient to cause significant downstream effects.

MCBT: The targets of DUX4 gave you clues about roles about its role in development. Can you discuss this a bit?

LG: The targets of DUX4 include those involved in spermatogenesis as well as early embryonic development. We’ve also found that other double homeodomain proteins, including those from other species, are also expressed in the germline. This points to a possible conserved role for DUXs in regulating early developmental processes and reproductive biology.

MCBT: You completed your PhD in a little over three years. Congratulations! How were you able to do it?

LG: Thank you! Other than spending many nights and weekends in the lab, I think many other factors came together for me: a) my mentor, our fearless leader, Stephen Tapscott, whose wisdom, support and enthusiasm propelled this project forward; b) my labmates, who were not only great scientific colleagues, but also my mentors and social support; and c) a heavy dose of luck! A couple of other things that helped me be more efficient in the long run are: 1) Not being afraid to let go of a project, no matter how much time and sweat was spent on it already. It’s a hard thing to do sometimes, but the sooner you let it go, the sooner you can start the next exciting thing that may turn out to be the core of your thesis! 2) Read, read, read, especially in the beginning. It was easy to put off reading articles, especially when you’re trying to be productive and generate data in the lab, but I think perusing broad-based literature and putting my work in perspective helped save me time in the long run.

MCBT: What were the biggest hurdles to overcome with the project? How did you tackle them?

LG: The biggest hurdles were definitely technical issues. For example, RT-PCR is a fairly straightforward technique, but running RT-PCR on a repetitive and highly GC-rich retrogene expressed at an infinitesimal level is riddled with problems. Tackling these issues required methodical action, numerous controls, as well as optimization and troubleshooting with the help of the rest of the FSHD team. Another big hurdle was the lack of available tools to study DUX4, including antibodies. There were no commercially available antibodies to DUX4 and only one antibody produced by a lab overseas. I spent a lot of time in the initial phases of my project developing numerous antibodies to DUX4 for use in western blots, immunoprecipitation and immunohistochemistry.

MCBT:  How do you think being an MSTP student impacted your approach tograduate school? To medical school?

LG: Intellectually, I think being an MSTP student has enhanced my insight into the applications of basic science research conducted in graduate school and also deepened my understanding of disease mechanisms that I learn in medical school.

MCBT: Did you feel pressure to get back to the second half of your MD training quickly? If so, how did you deal with it?

LG: As an MSTP student, I definitely do feel a time pressure, since our program consists of four years of medical school in addition to the variable number of years spent in graduate school. After that, most of us still have to do years of residency training and/or possibly a post-doctoral fellowship, depending on what path we choose. This pressure did help to motivate me to work harder and to work more efficiently. However, I didn’t feel “rushed” in the sense that I had a deadline. I truly enjoyed graduate school and wanted to learn as much as possible. It wasn’t easy for me to leave my lab and return to this starkly different world.

MCBT: How has the transition back into MD training been? Are you doing clinical rotations now? Any likes or dislikes so far?

LG: The transition back to clinical rotations was pretty rough. I was dropped into the inpatient hospital service for Pediatrics at the Madigan Army Hospital. Honestly, I had no idea what I was doing at first! Plus, I hardly remembered anything from medical school classes I took four or five years ago. Things improved as I familiarized myself with the structure and culture of the teaching hospital. Clinical reasoning is interesting and challenging in its own ways, but I must say I am not a fan of the loads of rote memorization that is still required. I do very much enjoy the patient interaction and seeing the diseases described in textbooks come to life. I haven’t seen a patient with FSHD as a medical student yet, but that would bring an amazing connection in my training as a physician scientist.

MCBT: Do you have any inklings about what you might specialize in, in terms of medicine, in the future?

LG: I don’t have any preconceived notions about what I will do for the future. I’m keeping an open mind as I go through the various clinical roations. However, I am leaning more towards internal medicine specialties that place a greater emphasis on understanding pathophysiology and that are conducive to a research career as well.

MCBT: Do you think you’ll incorporate research into your future career? If so, what might you work on?

LG: I love research and teaching, so I definitely hope to incorporate those into my future career. There are so many things that interest me, so I’ll just have to wait and see to which field the road takes me.

MCBT: What do you do for fun outside of school/work?

LG: I spend time with my fiance and our dog, Sesame. We go out for bike rides and runs. I also enjoy playing soccer, photography and gardening—when I have time!

MCBT: How does it feel to have your work recognized by the Weintraub awards?

LG: I feel absolutely honored and extremely lucky to have been recognized by the Weintraub award. As I mentioned previously, many factors contributed to the success of my thesis project, so I would like to share the honor of this award with all of those who helped me along the way and especially my mentor Stephen, the FSHD team and my fellow labmates. I stand on the shoulder of giants.

Do you know of MCB student accomplishments, scientific or otherwise, that you’d like to share with the Transcript? Let us know! Email us at mcbtranscript@uw.edu.

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