You are hereDecember 13, 2013
2013 Winner: Laura Shin
“A Labor of Love”
Laura Shin, Ph.D., is the recipient of the first Young Investigators Award bestowed by STEM CELLS Translational Medicine. She earned this recognition by teaming up with internationally recognized stem cell biologist Daniel A. Peterson, PhD., to introduce a phenomenon of stem cell recruitment in would healing that had not be explored previously.
The paper, “Healing by Recruiting Existing Endogenous Tissue Stem/Progenitor Cells Human Mesenchymal Stem Cell Grafts Enhance Normal and Impaired Wound,” describes the potential for grafted mesenchymal stem cells (MSCs) to recruit other MSCs that naturally occur in the body and then mediate repair. It was originally published online Dec. 21, 2012, in SCTM. The paper has also garnered a F1000 prime article recommendation.
Currently a dual podiatric medical and doctoral student at Rosalind Franklin University, Chicago, Dr. Shin’s goal is to become an academic clinician performing research in wound care and diabetes in a university setting. She earned her doctorate in 2012 under the mentorship of Dr. Peterson, who established Rosalind Franklin’s Center for Stem Cell and Regenerative Medicine. During her time in his lab she was the first and only DPM/PhD candidate to be awarded the prestigious American Diabetes Association’s Clinician Scientist Training grant for her work with bone marrow-derived MSCs in diabetic wounds. She completed her Ph.D. with distinction.
SCTM talked with Dr. Shin last month, shortly after she learned of her Young Investigator’s Award.
SCTM: How does it feel to be the first to receive STEM CELLS Translational Medicine’s Young Investigator’s Award?
LS: It was very exciting and also very surprising because the award has come so early in my career. I had applied earlier this year and forgot about it. I had never expected to win. Then you heard you’ve won and re-read the notice over and over to make sure it’s really your name. My first reaction was, "Who? Oh my goodness!"
SCTM: Well, congratulations. Could you talk about the hypothesis you were testing with the research in your paper?
LS: We were testing how a person would respond to stem cell therapies and if they were able to mount their own response to these therapies. In particular we were looking at Type 2 diabetic patients. Would they be able to heal as well as a person without a disease or without being in a chronic disease state?
We were seeing how stem cell therapies affected the person individually and if we could mount an innate response to these therapies to different things like chronic wounds. We found that using our stem cell therapies not only helped heal the local environment, they also helped mount a systemic response.
SCTM: Why is that important to stem cell research?
LS: We put more emphasis on the host. We began to view stem cells as initiators instead of the cells that were ultimately responsible for repair. We asked ourselves, “If we were able to introduce those cells to the right environment, could the body take over and heal itself?”
We approached this by using an animal model that expressed Type 2 diabetic phenotypes like high blood sugar, neuropathy, retinopathy and obesity and had difficulty healing. We were seeing if they were able to mount the same response as their healthy counterparts and what sort of signals were up-regulated in using stem cell therapies.
We think that's important in furthering the stem cell field, because we were able to see significant differences in the host response in a healthy vs. diabetic subject. We also studied the different factors that were introduced by exogenous stem cell therapies and the ones that were innate.
SCTM: Was there any specific methodology that was particularly important to this study?
LS: I developed a novel asymmetric wound mouse model to compare the local environment vs. the systemic environment and also to compare what the grafted cells were doing vs. the whole body. The theory behind this model is to create two wounds: one side would receive cells while the other would get none. We would then be able to compare the difference between direct engraftment and the subsequent effect that those cells and signals would have on the rest of the body, including the wound that had “no therapy.” What was most surprising to us was that the side that did not receive any cells never had contact with the engrafted stem cells but still showed improvement in healing.
For this particular study, using human cells was very important, too. One of the biggest drawbacks to stem cell therapies is oftentimes you put the cells into the body and then you're not really sure what happens. Are the results due to the body's own response or is it because of the cells that were implanted?
We were fortunate enough to use mesenchymal stem cells (MSCs) that allowed for cross-species interaction, so we were able to implant human cells into the mice and see whether or not they were just incorporating into the local area or if they were traveling to other parts of the body such as other organs or the bone marrow.
What we found was that, initially, the implanted cells kick-started the healing process and quickly disappeared. Long before the repair was complete, the mouse's own cells took over. We initially thought it was just the therapies themselves that were doing all of the work, and were very surprised to learn that it was the mouse's own cells that were bringing in these different factors.
There was an influx of the mouse’s own stem cells that were coming to the area. They were kind of like a self-feeding loop. More cells would come and help, and then they would recruit other innate cells to the environment to help out, too.
SCTM: What do you think that means for stem cell biology?
LS: It means that stem cell therapy can approach the body in multiple different ways. Stem cell grafts are able to communicate with the body so it's not just a local effect; they are actually able to “tell” the rest of the body, "Hey, this isn't working, we need more help."
In the field of MSCs, many mechanisms really aren't understood. I think part of the reason is that it's not only the stem cell therapies that we're putting in, but it's the body's own response to that therapy that's helping out and contributing just as much.
We hope what that means is in the future we can have more targeted therapeutics so that we can just introduce the right signals and find ways to increase the body’s ability to heal itself.
SCTM: What do you think should be tested now?
LS: The next step is to look at individual factors to see if they are sufficient enough to mount the same type of response. We started this in the paper, and what we were finding was that certain signals that were being elevated were actually recruitment factors.
So we're thinking that maybe a cocktail of different recruitment factors — taking the body's own stem cells and getting them to that area — should be the next step.
I had another paper where we looked at the endogenous state of stem cells, comparing animals at some baseline level without any therapeutics at all to see where they were. These animals in a chronic disease state seem to have a lower number of viable stem cells in general. So our next step is to find ways to improve the stem cell environment in patients with chronic diseases.
SCTM: You were talking earlier about recruiting cells. Can you explain what you mean by that?
LS: We’re talking about getting specific cells to the area of the injury. My primary area of interest is wounds, like diabetic wounds that you often see in the lower extremities, especially the feet and legs. A lot of therapies are concentrating on the local environment only — maybe they’re putting on grafts or using a matrix type of therapy.
What we're hoping to do is connect some signals to these wounds so we can kick-start the body to get out of that inflammation stage and get innate MSCs into that area to regenerate and create new blood vessels and epithelium and maintain closure.
SCTM: Why did you select Stem Cells Translational Medicine to publish your paper?
LS: I think a lot of clinicians are using stem cell therapies without actually knowing the mechanisms behind them, and there are a lot of scientists who understand these mechanisms and have great potential therapies. So it’s exciting that there's a translational medicine journal out there to bridge the gap between clinicians and scientists. This is very vital to clinical trials right now. As a clinician-scientist, I thought what a great opportunity to publish in a journal that values that connection between the two worlds.
SCTM: What's the best scenario that you would like to see come out of your study?
LS: I would love to see this work continued and to develop therapeutics that improve the health status of patients with a high risk of complications. Perhaps we could pinpoint enough factors to introduce to get patients to the point where we can get these wounds to heal.
We also want researchers to start looking at the endogenous factors, at the deficiencies in the body. We could really further the field of stem cell research in that way, because stem cell research is not only about grafting stem cells, it's also about studying the stem cells within your own body and understanding and harnessing their capacity for healing each individual person.
It's a great direction to go.
SCTM: Is that what brought you into stem cell research in the first place?
LS: Originally my area of stem cell research was in the brain. That's how I got introduced to Dr. Peterson, who is very well known in the neuroscience field as well as the stem cell arena. I was working with a child with cerebral palsy for several years and became very interested in traumatic brain injury, especially hypoxic ischemic lesions associated with cerebral palsy.
For decades, the adage was that there was no regeneration in the brain or in the nervous system at all. To see different labs question that, to harness those regenerative capacities in different areas of the brain to see if you can improve the quality of life for a lot of these patients, is very exciting.
When I chose my career, I decided to pick a surgical specialty so I went into podiatry — foot and ankle surgery. I saw the devastating effects of diabetic wounds, what it actually meant in a person's everyday life to not be able to walk. It affected everything, from their jobs to their personal lives, and they were constantly coming in. You would heal one wound and all of a sudden get another wound. It was a consistent problem and a huge healthcare burden.
It is so exciting to see the potential for something like stem cell therapy that could help regenerate these areas, especially something so chronic and difficult as these types of wounds.
SCTM: Tell us about your education and training. What drives you?
LS: I graduated from Johns Hopkins University pre-med with a neuroscience degree and did a lot of research during my undergrad in different fields, but mostly in regenerative medicine looking at some facet or another of stem cell research.
After I graduated, I spent two years at Northwestern Children's Memorial Hospital and published a few papers looking at stem cells in brain repair and hypoxic-ischemic studies — basically what would happen to a patient with stroke or a child with cerebral palsy — and seeing if there was use for stem cell therapy in the brain.
I realized that I really enjoyed research, but I wanted to get into clinical medicine, as I loved working with patients. It was very difficult for me to figure out what I wanted to do, because I also knew that I wanted a family and to be a surgeon. It was difficult to balance all these different wants, but then I spoke with somebody who had done podiatry and they were able to do surgery and kind of a mix of everything and loved it. They had a great home life as well.
I grew up not too far from William M. Scholl, the school of podiatry in North Chicago, and there was an opportunity for me to do research there. There is a great research center called CLEAR (Center for Lower Extremity Ambulatory Research) with faculty members who are passionate about research, such as Dr. Stephanie Wu. At the time Dr. Lee Rogers and a DPM/Ph.D. named David Armstrong recruited me to do the stem cell project. They were very enthusiastic about my background and told me "You couldn't have come at more perfect time." So the stars sort of aligned in that general direction.
It was a pretty unique experience, because there are not many people in podiatry doing research in the laboratory setting, and it was a unique opportunity for me to do some bench work. It was a huge opportunity.
So I did my two clinical years of podiatry — it's a four-year program altogether — and then completed my Ph.D. During my doctorate work I applied for an American Diabetes Association Clinician-Scientist training award and won. I was the first DPM/Ph.D. student to receive such an honor. Getting this award through the American Diabetes Association was huge for me. I was able to dream big and develop the study to the scale I wanted.
SCTM: There's a long list of awards you've won.
LS: I was very fortunate in a lot of ways. My mentor Dr. Peterson, faculty and administration at Rosalind Franklin University and my attendings in the field of podiatry have been so supportive. It typically hasn't been a field that has done a lot of translational research. A lot of clinical research has come out of here, but again, there's not a lot of bench work.
I had great shoulders to stand on, people that have always inspired and guided me throughout this entire process. The dean of the university, Dr. Nancy Parsley, has played a major role in my education and has always encouraged and given me the resources to pursue these endeavors.
I think my research values the importance of the correlation between the lab and the clinic. I’m constantly looking for ways to improve patient care. My studies were never just about podiatry research, it really was much more global. We’re hoping that these studies will really work for a lot of patients. This applies to anyone with a chronic disease state, not just diabetes. It could be patients with leukemia or with any sort of immunodeficient disease in general.
SCTM: Tell us a bit about your current position.
LS: I'm finishing my podiatric medical degree right now and have been doing different externships, looking for residency placement at this point. This award comes at a perfect time because I have my residency interviews in January. I can tell them about it and, hopefully, they will view me as an asset to their program.
It's an interesting balance for me to come back into the clinical world, because I see how important the work that I did in the lab was clinically. Every element and every aspect of what I've been through has made me a more well-rounded clinician.
I can appreciate where the limitations lie and how difficult it is when you get patients that aren't compliant. There are lots of patients who have difficulty with what needs to be done. For various reasons, their lives just aren't able to accommodate the time and effort that it takes to get better. So I can see a huge need for therapies that are not only more cost effective, but also more time effective as well.
I want to become an academic clinician and have some affiliation with a university and be able to teach and inspire other clinicians and podiatrists, and continue to ask questions. We are on the frontlines. We see a lot of the things that are touching the patients and can bridge that gap between scientists and clinicians.
I think if we had more communication in general — and I think these journals are the right platform to get people to talk with each other, to see the problem and to see solutions — I think we'll wind up with a very promising future of better therapies and patient care.
SCTM: Is there anything else that you think is important to bring up about your paper, about your work, about what you're thinking next?
LS: The paper was a labor of love. I thought long and hard about how this was going to affect what was already out there in the field. For a long time people have believed that if you improve the blood sugar, if you give patients medication to treat the symptoms, they'll automatically get better. I think that this paper expresses that it can be more complicated than that.
And I think that health-wise we have to start looking even deeper, at the overall health status of the patient inside and out. There is a lot of great work out there looking at metabolic memory and the genetics of patients with chronic diseases. We need to continually look at why certain patients are more susceptible to these types of complications.
As a child my first word was, "Why?" Why is this happening? Why are certain people affected? Why isn't therapy better? I think we should continually ask these questions because we can really advance the medical field when we ask why not, why this, why that.
That's why I'm so excited to get an award. I may appear to be rather young and very wide-eyed, but I hope to continually ask those questions and to constantly search for answers, and to really love what I do.
And I think that's what so gratifying. I truly enjoy what I do.
Click here to read the best papers from our 2013 Young Investigators.