Connecting the Dots in Pediatric Research

Clinical and translational research leaders join forces to remove traditional barriers and accelerate progress against rare and dangerous childhood diseases

by Shawn Oberrath

Understanding and repairing the deepest mysteries of pediatric diseases are big tasks for both basic and physician scientists, but at MUSC Children’s Health these two groups are working together to discover more treatment options and help patients recover.

In 2018, work was well under way to build two top-tier clinical facilities that would launch MUSC Children’s Health to the highest level of pediatric care in South Carolina and the whole Southeast region: the world-class MUSC Shawn Jenkins Children’s Hospital and Pearl Tourville Women’s Pavilion and the comprehensive, kids-only R. Keith Summey Medical Pavilion. At the same time, scientists at the Darby Children’s Research Institute (DCRI) were studying childhood diseases from the lab bench. The DCRI was created to be a center of innovative and collaborative pediatric research and is one of just 15 dedicated pediatric research institutes in the country.

Against this backdrop, Andrew Atz, M.D., chair of the MUSC Health Department of Pediatrics, needed to hire new heads of both clinical and basic research who could collaborate meaningfully and connect the dots between the clinic and the lab bench.

“At MUSC Children’s Health, we are imagining what’s possible for each child by providing the expertise every child needs and deserves,” Atz said. “History has shown that the best way to optimize patient care is to take what we learn in research labs and apply it to enhance that care.”

With that in mind, Atz recruited John Costello, M.D., MPH, vice chair of clinical research for the Department of Pediatrics and director of research for the Children’s Heart Center, and Denis Guttridge, Ph.D., director of the DCRI. These two leaders represent the pediatric clinical and basic research worlds, respectively, which at some institutions live far apart both physically and figuratively. But thanks to Atz’s strategic recruitment and support, MUSC gained two leaders who are experts in their own worlds and have teamed up to craft a united vision.

This leadership duo — combined with the rare tandem of a dedicated pediatric research institute plus a major children’s hospital — will propel research at MUSC toward better, safer treatments for childhood diseases that can be severe and even life-threatening. And more than just sharing a vision, both leaders are implementing ways to boost faculty, researchers, fellows and residents over traditional barriers that can hold research back.

“Together we have a pulse on both what's happening on the clinical side and what's happening on the basic science side,” Guttridge said. “And we have the unique opportunity to identify where the barriers are and then figure out how to best bridge the gap between basic scientists and clinicians.”

Recognizing roadblocks

Between basic and clinical research rests a bridge: translational research.

Basic science research generates new knowledge that doesn’t necessarily address a clinical issue, as explained by Costello, but translational research is done with a specific patient problem in mind, like pediatric cancer or a type of heart disease. Clinical research involves direct interactions with patients, such as drug trials, behavioral studies and analyses of patient data and surveys.

In an ideal situation these research avenues feed into each other so that discoveries at the lab bench lead to solutions at the bedside — from cell culture to animal models to clinical trials. New samples and knowledge from trials can be sent back to the lab for further refinement, creating a virtuous cycle of new knowledge, safer drugs and better outcomes for patients. For this cycle to function well, the partnership between scientists and clinicians is essential — physicians lead clinical trials, but they need to work with scientists to determine if and how a treatment worked. And scientists need physicians to funnel the best research into clinical trials and open up new options for patients.

“This partnership is absolutely critical from the very first result in the lab to the possibility of a clinical trial,” Guttridge said.

But in the real world things are complicated, and collaborations can be held up by fundamental obstacles like geography and time commitments.

On medical campuses, the clinical activities and clinicians are typically clustered in hospitals and outpatient clinics, and the basic and translational researchers are housed in different buildings elsewhere. In addition, clinicians and scientists often work 60 or more hours a week.

Costello emphasized that it takes extra time and energy to find and pay attention to the work that's being done by one’s counterparts on the opposite side of campus. So a potentially powerful team working on related problems or using related technologies or skills could be a short walk across campus from each other, but unless the groups are aware of each other’s efforts they may never connect.

Smoothing the path

With their passion for uncovering treatment options for the rarest and most dangerous childhood diseases, Guttridge and Costello are determined to surpass any such obstacles between their divisions, and the key is to start working together early. They have thus championed multiple initiatives to gather colleagues and resources and create an environment where the clinical and translational arms of research can work together cohesively.

"We have the unique opportunity to identify barriers and then figure out how to best bridge the gap between basic scientists and clinicians" - Denis Guttridge, Ph.D.

Both leaders emphatically agree that the goal of better treatments for patients is the most important driver of their hybrid collaborative model. But there are other benefits as well — new and innovative findings are crucial for career development and retention of clinicians and researchers and for efficient use of resources. There can also be opportunities for outside funding and the inherent reward of “cracking” diseases that currently have no answers.

Each division within the Department of Pediatrics has a unique level of research interest and infrastructure. After speaking regularly to each of the 17 division heads, Guttridge and Costello realized just how much clinicians and basic scientists could help each other.

For example, a division might want to develop a fellowship program to recruit fellows who are both residents and scientists, but until the research infrastructure is firmly in place the faculty and staff will need help to make it work. This situation is exactly where Guttridge and Costello can step in and assist by using their complementary savviness and leadership assets — one in the resources, personnel and workings of the clinic and the other in the realm of the laboratory.

Guttridge explained that as a top research hospital, MUSC needs to be engaged in research at all levels to find the next cure for the next disease, from nephrology to cardiology, neurology to infectious disease, and emergency medicine to cancer. And this high leveI of effort must be driven by clinical trials and by the science that propels treatment options into the clinic.

Right now not all divisions are set up for that, but as the Department of Pediatrics grows the two partners plan to integrate more give-and-take among divisions, not just within individual groups. Although this may seem like a straightforward next step, this is a special part of the MUSC environment.

“These types of interactions don't happen just anywhere,” Guttridge said. “They have to come from the very top, and our department chair fosters that environment.”

Moving into high gear

One game-changing initiative that has ignited passion amongst MUSC’s pediatric researchers is a competitive internal grant program that awards two $50,000 grants for promising research projects — one translational and one clinical. This pilot funding gets projects started and aims to launch them to the next level — securing external funding for larger projects and even more impactful research. Importantly, the internal grant funding is made possible by many generous donors dedicated to philanthropic support of MUSC, highlighting another pillar of the ongoing cooperative efforts. 

The grant program launched in 2019, with awards for the 2020-2021 fiscal year. The first clinical grant award winner was Laura Carpenter, Ph.D., a pediatric development specialist who submitted a telemedicine project focusing on autism.

Autism is a common pediatric disorder, and Costello explained that the telehealth aspect became timely because of the looming global pandemic. “Being able to provide the expertise that exists in academic medical centers to folks who don't live in the big city or live out in more rural areas and to make sure that it is effective when it's delivered by telehealth is very important,” he said.

The first translational grant award winner was Jezabel Rodriguez-Blanco, Ph.D., a pediatric cancer researcher who submitted a research project to understand why cells of the aggressive cancer medulloblastoma become resistant to chemotherapy. She hypothesized that a specific stem cell target may drive resistance in this cancer, and she hopes that understanding that target will lead to more effective treatments for this deadly brain tumor.

Both researchers will present their findings at the 13th Pediatric and Darby Children’s Research Institute Symposium this spring. The annual symposium is another important tool for Guttridge and Costello, and they’ve placed a lot of effort into improving it by including a blend of presentations by both clinical and basic science investigators.

In keeping with the goal of cross-pollination between disciplines, Guttridge invites nationally recognized experts to speak at the DCRI, and he makes it a point to invite all the clinicians and clinical investigators to hear those presentations and exchange ideas with the visiting professors. This is one more example of giving people time to be in the same room at the same time, whether they are fellows, clinical investigators or foundational scientists. And while these days being in the same room might just mean being on the same video call, the goals of fostering relationships and a collegial environment remain intact.

The research faculty within the DCRI has been enthusiastic about the changes and involvement by Guttridge and Costello. Pediatric neurosurgeon and researcher Ramin Eskandari, M.D., said that Guttridge is both involved and knowledgeable. “When researchers give lectures or ‘chalk talks’ to improve their grants and papers, he listens and engages," Eskandari said. "He and Costello have also opened up new avenues for tissue bank storage at the DCRI so we can have tissue samples from kids for all the different specialties. All these little things are creating new avenues for research.”

Pediatric cardiologist Eric Graham, M.D., agreed. “Globally the gap between basic and clinical research has widened with the increasing sophistication and specialization of both,” he said. “Bringing advances in basic science to improve clinical care requires collaboration, and our leaders have worked hard to bring basic and clinical scientists together.”

“Research is not easy, but we're creating an environment that will cultivate relationships and make it as graceful as possible for all of our investigators to be successful” - John Costello, M.D., MPH

Both Guttridge and Costello acknowledged the enthusiasm from faculty in regard to the grant program in particular. Physician scientists who come to an academic medical center do so because of their passion for their patients and their research, and they have spent most of their lives training for this role. Having an environment that supports this passion is invaluable — they now can get busy doing what they were trained to do at the highest level.

Looking down the road

With new initiatives under way despite the setbacks created by a global pandemic, Guttridge and Costello will refine their hybrid collaborative model and continue to foster a collegial environment for researchers and clinicians across the board. For example, they hope to set up laboratory training for residents and fellows, continue to integrate local meetings and symposia, and build an open environment for teamwork.

They will also perform targeted recruitments of clinical scientists and research faculty to enhance the ranks of outstanding researchers already at MUSC. The DCRI currently has 12 dedicated faculty who are basic scientists or physician scientists representing different divisions of the Department of Pediatrics.

Guttridge hopes that eventually the institute will be able to support research across every discipline. “The vision is that with the collaborations we make with physicians we can fulfill their needs and grow so that the research can benefit the whole clinical enterprise,” he said.

“Research is not easy,” Costello added. “But we're trying to create an environment that will cultivate relationships and also provide infrastructure, space and supportive personnel to make it as graceful as possible for all of our investigators to be successful.”