Pioneers of Hope

At the Monroe Carell Jr. Children’s Hospital at Vanderbilt, our physicians’ work extends beyond patient exam rooms. They are also scientists – searching for discoveries to offer better treatments, and hopefully, find cures for their pediatric patients. The four doctors profiled here represent only a sampling of the physician-scientists working tirelessly to make Children’s Hospital a place of unwavering hope.

 

It’s left brain and right brain, scientific and creative. That’s what interested Bret Mettler, M.D., in heart surgery.

“I liked that you could be somewhat artistic but at the same time it requires precise technical skill, and those are two very distinct thought processes,” said the assistant professor of Pediatric Cardiac Surgery. “In addition, I find it extremely rewarding taking care of patients, especially sick children. They didn’t choose to have their diseases, and it’s a privilege to care for them and their families.”

Since Mettler arrived last year as the new director of Pediatric Cardiac Transplantation, more children are receiving state-of-the-art heart failure care and a renewed chance to grow up healthy and happy.

Under his guidance, the use of mechanical support devices for children has been expanded, allowing them to remain candidates for cardiac transplantation until a donor heart is available.

Mettler has also helped expand the criteria that make patients eligible for a heart transplant. Some patients who have had previous cardiac surgery have antibodies that make them more likely to reject their donor heart. A new protocol developed at Children’s Hospital to remove the antibodies exchanges the patient’s blood volume in the operating room.

In addition, a process called plasmapheresis is incorporated after surgery to remove additional antibodies that can cause rejection. In the past three months, two “highly sensitized” patients have had successful transplants.

“These are kids that six months ago we would have never been able to transplant and would die. Now they have a new heart and show no signs of rejection,” Mettler said.

Children’s Hospital is also initiating an “ABO-incompatible transplant” program, which means the donated organ does not match the patient’s blood type.

“This is immunologically challenging but for a select group of patients, will allow us to broaden our use of allocated organs. This is especially important in our newborn patients where the organs are most scarce. By initiating this program, we hope this allows us to transplant those kids sooner, before they need mechanical support or become too sick to obtain a heart transplant,” he said.

Mettler attended medical school at the University of South Dakota, his home state, and performed his general surgery residency at the University of Michigan Medical Center in Ann Arbor.

Before coming to Monroe Carell Jr. Children’s Hospital at Vanderbilt, he was at Children’s Hospital Boston, where he performed a congenital cardiac surgery fellowship and a research fellowship in cardiac tissue engineering.

Mettler’s research is in heart valve tissue engineering, with the goal of creating heart valves that grow with children.

“Some children have multiple operations in their life for valve repair or replacement. If we could implant a valve constructed of their own tissue that remodels and grows with the child’s growth, we could dramatically change their quality of life, not to mention avoiding the risk of multiple heart surgeries,” Mettler said.

Mettler says fatherhood has made him more sensitive to the needs of his patients and families. He and his wife, Kelly, recently celebrated their daughter Harper’s first birthday.

“It makes you very sympathetic to their pain and suffering but also helps you celebrate their joys and their successes,” he said. “Each day, I am honored to care for our patients and their families and feel privileged to be a member of the Children’s Hospital.”

– by Leslie Hill

•••

A glass bottle of bright orange Nehi soda sits in the office of Lisa Young, M.D., a gift from a patient with a lung disorder called neuroendocrine cell hyperplasia of infancy, or NEHI. The retro soda pop bottle bearing the same initials as the lung disorder serves as a reminder for Young of the great advances in the disease.

She hopes to make further progress as director of the new Rare Lung Diseases Program at Monroe Carell Jr. Children’s Hospital at Vanderbilt.

Children with NEHI usually present in the first few months of life with very rapid breathing, low oxygen levels and trouble growing because all their calories are used for breathing. A lung biopsy was required for a diagnosis until Young and collaborators at several children’s hospitals discovered a lung pattern visible through chest CT scan.

“The disorder didn’t even have a name until 2005. It’s very rewarding that in just a few years’ time we’ve been able to transform how we diagnose this disorder into a way that’s a lot less invasive and saves these children from having surgery,” said Young, associate professor of Pediatrics, Medicine and Cell Biology.

After medical school and residency at Duke University, Young performed a pediatric pulmonary fellowship at Cincinnati Children’s Hospital and then joined the faculty, establishing the country’s first pediatric rare lung diseases program there.

Young came to Children’s Hospital in January to establish a similar program, creating an umbrella to provide care for children with chronic lung conditions.

“The idea is there needs to be a medical home for patients who may not fit under a category like asthma or cystic fibrosis but still need a coordinated team approach for chronic health care delivery,” Young said.

One of the major advantages of an umbrella approach for rare diseases is the research potential, and Young says Children’s Hospital is uniquely positioned to leverage the technology and expertise of Vanderbilt University Medical Center to solve clinical problems.

“Providing our current best care isn’t enough for these disorders. We still don’t know enough about the causes, long-term outcomes, or how to effectively treat or prevent many of these disorders. So, we’ve got to take the next steps and try to get to those answers.”

A rare disease is defined as one that affects less than 200,000 people in the U.S., and there are actually more than 7,000 known rare diseases, over half of which predominantly affect children. In addition to NEHI, there are many different forms of interstitial lung diseases and lung development disorders that Young and colleagues treat and research.

“They may be called rare diseases but they’re not rare to the family going through it. As a physician sitting with one family, that child counts as much as any other,” she said.

“These children are quite sick, with many requiring supplemental oxygen for years. They often go through many hospitalizations and extensive testing, traveling great distances for specialized care. We partner with these families to make progress together. And my passionate opinion is that research needs to be a central part of our mission to help these patients.”

With a centralized clinic and dedication to research, major advances, like the one made for diagnosing NEHI, are a growing reality for all patients with rare lung diseases at Children’s Hospital.

If she’s not seeing patients in the clinic or doing research in her lab, Young stays busy with her husband, 11-year-old daughter and 8-year-old son.

– by Leslie Hill

•••

The fountain of youth and time machines are the substance of good science fiction novels or movies. For Jonathan Schoenecker, M.D., Ph.D., they are the possibilities of great scientific research.

Schoenecker, assistant professor of Orthopaedics, Pharmacology, Pathology and Pediatrics, believes the answers to slowing the aging process and improving wound healing lie in the human coagulation system, the process in which our bodies make and break clots. For years, his lab has been entrenched in studying the role that coagulation plays on skeletal development, orthopaedic healing, cancer and other infections.

“What we are figuring out is – kids heal so much better than adults because the same blood vessels that heal a wound are the ones that help you grow. There is no other way to put this – I think this is the fountain of youth,” he said.

“If we can figure out in the adult population how to turn your coagulation system back to what it was when you were a child, we believe that you can change aging, osteoporosis, wound healing, fracture healing and nerve healing by allowing these blood vessels to return.”

To test his theory that the clotting system is a key element in the healing process, his lab genetically manipulates the coagulation system of young mice to essentially that of adult mice. Indeed, they found that the mice stopped growing as they lost the ability to support the blood vessels necessary for skeletal development. In addition, they found that these same mice cannot heal bone fractures.

“Our ultimate goal is to figure out how to give a drug that would restore the coagulation system to that of a child until the wound heals,” he said. “Unfortunately, most current drugs that can change coagulation also have the bad side effect of increased risk of bleeding. So the Holy Grail is designing a therapy that matches what we see in children, one that decreases a chance of thrombosis, without causing bleeding. We need to figure out the exact balance.”

Schoenecker also treats an array of pediatric orthopaedic conditions, including broken bones and infections. Influenced by his father, also a Pediatric Orthopaedic surgeon from St. Louis, he has a strong interest in developmental problems of the hip joint including Developmental Dislocation of the Hip (DDH), Perthes disease and Slipped Capital Femoral Epiphysis (SCFE). Together, these three disorders account for 70 percent of hip replacement procedures performed in the United States.

With research, and in some cases surgery, Schoenecker hopes that hip osteoarthritis requiring replacement can become a preventable disease if treated properly during adolescence.

Schoenecker spends a full day in clinic, on trauma call and in surgery, and the rest of his time in the lab. His bench-to-beside practice is a win-win for patients and his lab colleagues, he said.

“My ultimate goal is to be able to explain to my patients and families what exciting experiments we are doing in the lab in a manner they can relate to their disease,” said Schoenecker. “Through the incredible work of members of my lab and the opportunities offered by the Children’s Hospital and the chairmen of Orthopaedics, Pharmacology and Pathology, so far it is working. It’s the most wonderful thing in the world.”

Schoenecker graduated from Duke University Graduate School and did his residency training at Vanderbilt. He completed his fellowship at Children’s Hospital in Boston and joined the Vanderbilt faculty in 2009.

– by Jessica Pasley

•••

The writing was on the wall (sort of) for Patrick Grohar, M.D., Ph.D., to become a physician-scientist.

“My third-grade teacher told me my handwriting was so bad that I should be a doctor,” joked Grohar, assistant professor of Pediatrics, Hematology and Oncology. “That stuck with my mom (also a teacher) who encouraged that train of thought.”

Perhaps it was Grohar’s love for sports and science that led him on a collision course with the medical and research worlds.

As a mid fielder in lacrosse, he was disciplined, focused and committed. He mirrored those skills in science, showing dedication in the lab where his attention was on research and chemistry.

“A lot of athletes want to do medicine because, like sports, it takes a lot of discipline and commitment,” said Grohar. “It’s the same type of focus – being able to do competitive things over and over with focus.”

Grohar arrived at Vanderbilt University in January from the National Cancer Institute (NCI), bringing with him his passions and self-motivation in lab-based work.

His research focus is on drug discovery in pediatric sarcomas, cancers that develop in bone and soft tissues. Specifically, he studies Ewing’s Sarcoma, a cancerous tumor that grows in the bone, often during puberty. He is developing new therapies to block a cancer-causing protein EWS/FlI1 expressed in patients with Ewing’s.

One of the identified compounds, mithramycin, will be the subject of a trial at the National Cancer Institute, a study that could be expanded to include Vanderbilt.

“Moving forward we’re looking to improve the activity of the drug, minimize toxicity and make it a true molecularly targeted therapy,” he said.

“Vanderbilt is the place where the facilities exist to do this type of work, and with the commitment being there I think it’s really an opportunity for our Medical Center.”

Grohar received his Bachelor of Science in Chemistry degree from Villanova University in Pennsylvania, where he also was a member of the Wildcats’ lacrosse team. He earned a Ph.D. in Chemistry from Wayne State University in Michigan, his home state, where he also attended medical school. He did a residency and fellowship at John Hopkins University, then moved on to become an instructor for the Pediatric Oncology Branch at the NCI.

His wife, Kristen Snyder, M.D., is an assistant professor in the Division of Hematology/Oncology in the Department of Pediatrics at Children’s Hospital. They have a 2-year-old son, Conor, and an infant daughter, Clare.

While much of his time is spent with his family and investigating sarcomas in the lab, he still makes time for sports, though more from a spectator’s angle. “My wife would say I have a sports problem,” Grohar joked.

He’s excited about the prospects and research opportunities available at Vanderbilt.

“It’s a great division. It’s really growing,” he said. “I love what I do, and I believe in the projects, science and education. I love having people in the lab and them getting fired up about science. I love teaching and seeing patients. I love being at work.”

– by Christina Echegaray