Margie Mathewson (margie.mathewson@gmail.com)

Graduate Program:  Bioengineering
Lab PI:  Dr. Richard Lieber
Undergraduate Institution:  University of Illinois Urbana-Champaign
Med-into-Grad Clinical training area:  Pediatric Orthopedics
Main clinical mentor:  Dr. Henry Chambers   hchambe1@san.rr.com

Quote:   “I have a totally new view on what I’ll do my future research on. While my thesis probably won’t change drastically, the focus of my research if I go on to a faculty position will be very different than it would have otherwise been. At this point, there are still MANY critical quality of life problems that could use a lot of work in the CP world. I’ve also realized that I need to keep talking to people living with CP. The patient’s perspective is the most important piece of information you can get when deciding what to study. Sometimes the things that seem critical from an outside perspective aren’t the key issues at all. I’ll be sure to find someone (or many someones) with CP to advise me on my research goals."

Rational for Med-into-Grad training:
My thesis aims to more completely understand the characteristics of muscle in children with cerebral palsy (CP) verses that of typically developing children. I’m using three methods to look at the tissue: 1) materials testing to look at the effects of connective tissue on the stiffness of the muscle, 2) cell sorting to determine the prevalence of common cell types in muscle, and 3) gene chip analysis to look at the specific contributions of individual sorted cell types on the overall gene expression at the tissue level. Because I’m using samples from pediatric orthopedic patients, Med-Into-Grad was a perfect chance for me to get to know the source of my research more directly. I hadn’t had much of a chance to talk with anyone living with CP prior to this program, and I knew participating would greatly improve my understanding of CP and of the concerns of patients and their families. I also really enjoy working with people, and this was a fantastic opportunity for me to get out of the lab and see the impact of my research on people in the real world.

Medical training and identification of medically-relevant research issues: 
My training can be broken into three components: 1) lectures and conferences, 2) time in the clinic, and 3) surgeries. I attended three to four lectures a week on various bone and muscle abnormalities and injuries. I also participated in weekly journal club and the short instructive courses given to the residents to help them prepare for their exams. In the clinic, we saw both typically developing sports injury patients and patients with CP or varying degrees of severity. This was helpful because it gave me a good picture of what the medical community views as “normal” as well as what the many manifestations of CP are. Surgeries, which happened on Tuesdays and Thursdays, let me see the problems within the body. I got to watch a wide variety of sports and CP surgeries on the lower extremities and hip. Over the course of my training, I learned the names and symptoms of many childhood musculoskeletal diseases and injuries that I didn’t previously know existed. I also developed a rudimentary ability to read x-rays, MRIs, and CT scans, which gives me new avenues to explore in my research. Most importantly of all, I got to talk to lots of patients and their families and hear more about what life with CP is really like. Patients ranged from nonambulatory and unresponsive to a professional soccer player on the USA Paralympics Team. Experiences varied widely, but I was able to determine that the critical abilities for all the patients were basic life skills (Can I communicate? Can I feed myself? Can I use the bathroom independently? Can I brush my own teeth?) and comfort. Everyone wants to live as independently as possible. Because of this knowledge, I’ll focus my research in my post-graduate career on these quality of life issues such as improving spasticity care (improved alternative to Botox, baclofen, and surgery) and basic limb use. Aiming high is good, but there is still so much farther to go on the basics.

Potential Research collaborations:
I discovered that there is still a long way to go in basic spasticity management. A drug or therapy that allowed effective control of unwanted movement and tone while not decreasing muscle strength and function during intentional movement would have a drastic impact on the lives of many of these patients. I think the first steps to finding an answer to this could be addressed by my planned thesis research (which was originally intended as a way to determine improvements in lower limb function only but which I now see could lead to understanding that will affect many areas of the body, some much more critical than the lower extremities) During my time in the clinic, I followed primarily Dr. Henry Chambers. I also spent some time with Dr. Maya Pring. I’ll be working with my MIG mentor Dr. Chambers, and a few of his colleagues on the rest of my thesis project. They provide me with both typically developing and CP tissue from their surgeries. As described in the first question, I’m trying to develop a better biological picture of what’s different in CP verses typically developing muscle, which I’m now hoping to expand to include determining possible components which could be targeted for new spasticity therapies.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
Being in the OR and clinic gave me a much more complete understanding of the options for patients with CP. Diagnosis is based on presentation of symptoms. Since CP is a very heterogeneous disease, the diagnosis serves mostly as a way to broadly categorize patients in order to determine possible treatments. As far as therapeutics go, there are oral or injected drugs (Botox and baclofen) or surgery. None of these options really provide a fully satisfactory outcome. The drugs all have side effects and don’t provide long term relief. The surgeries involve cutting or moving tendons in an attempt to improve range of motion and patient comfort, but cutting tendons and weakening muscle in patients whose muscles are already not fully functional leaves much to be desired. There is currently a gap in understanding what is happening in the muscle. If we could figure out exactly what components are causing the problem (are muscle fibers forming incorrectly? Is there too much connective tissue present?) we would have a better chance of developing a drug or therapy to target it.

Diagnostic & Therapeutic collaborations:
I’m still in the very early stages of figuring out everything that is going on in CP. My research is a long way from developing a therapeutic product, but understanding how cell types, gene expression, and muscle properties vary in CP muscle over a range of functional levels might offer a new way of looking at CP diagnostics. If we could classify patients by their cellular differences, we might be able to better understand which patients will benefit from which treatments. I’d like to get a little farther in my research before I discuss this with any of the doctors, since I just came up with the idea of looking at these characteristics as a way to diagnose patients during the MIG clinical rotation.

Long term impact: 
I have a totally new view on what I’ll do my future research on. While my thesis probably won’t change drastically, the focus of my research if I go on to a faculty position will be very different than it would have otherwise been. At this point, there are still MANY critical quality of life problems that could use a lot of work in the CP world. I’ve also realized that I need to keep talking to people living with CP. The patient’s perspective is the most important piece of information you can get when deciding what to study. Sometimes the things that seem critical from an outside perspective aren’t the key issues at all. I’ll be sure to find someone (or many someones) with CP to advise me on my research goals.

Student-specific experiences:
Be prepared: Throughout my time in Med-Into-Grad, I went constantly back and forth between planning out how I could get my masters and apply for med school as quickly as possible and sighing with relief at my good decision to go to grad school. If you’re someone who was on the fence before starting grad school, this will be sure to tip you one way or the other. In my case, this satisfied my desire for “doctor life.” I came out of the experience quiet certain that I had picked the right path with grad school, but excited to collaborate with medical professionals for the rest of my career. You, however, may be lured away to the medical world after you see what it’s really like.

Advice for new trainees--Autumn preparatory quarter:
My program was a little different since it was less formally organized. Other than doing the Med-Into-Grad classes and keeping in touch with the doctor I was working with, I had minimal activities in the fall. For future students, I think it could be helpful to get more involved with the ortho events. There are a couple of weekly activities, including journal club and radiology conference, that could be helpful for someone preparing to go in to the clinic and operating room. If you get the chance, learn the anatomy of the area you’re going to be studying very thoroughly, and be sure (at least for ortho) that you have a basic idea of what is going on in x-ray and MRI images.

Advice for new trainees—Winter clinical training quarter:
The most critical piece of advice I can give you is to make friends with the nurses, PAs, techs, residents, fellows, and anyone else you come across. The doctors are incredibly smart and helpful, but they are really busy, so these other wonderful people will share a lot in teaching you what you’ll learn. I found that the residents and fellows were a great source of information, since they had just gotten out of school and remembered what it was like to know absolutely nothing. If you’re in the operating room, the surgical tech/scrub nurse and the room nurse will be your two best friends. Be nice to them, because they’ll be the ones who can help you learn your way around the room, show you where things are stored, and help you get the best views of the surgery action. Everyone I worked with was amazing, and they patiently answered my hundreds of questions throughout my training. Dr. Chambers always gave me thoughtful answers and took my questions seriously, even when the questions were elementary and he was really busy. When you’re in the clinic, don’t be afraid of the patients. That sounds like silly advice, but some are fragile, or different than other people you’ve met, and it’s easy to stand in the corner and look on silently. When you get the chance to chat with them, be friendly. The little kids and their families were interested in my research and very excited about their disease being studied, and they were more comfortable with me once they knew why I was there. (Obviously, your role will be dictated by your clinical mentor, so play it by ear concerning talking to the patients).

Take home perspective on Med-into-Grad at UCSD: 
I’m sad to be ending the program! I would enthusiastically recommend Med-Into-Grad to pretty much everyone I know. Especially for those of us in clinically related research, understanding the patients as people in all their complexity changes the way we do research forever. I also found the preparatory course “Science Meets the Med Patient” completely fascinating. I had never had a chance to so closely integrate the disease (in a scientific context) with a real person. I’ve definitely got a much more complete picture of what I’m doing and why it matters.