May 28, 2019

The latest in cutting-edge research from across Texas Children’s Department of Surgery was recently on display at the 10th annual Edmond T. Gonzales, Jr. Surgical Research Day. The event is an important forum for surgical faculty, post-graduate trainees, nursing personnel and operating room staff to showcase their academic efforts in an encouraging environment.

More than 120 abstracts covering a broad spectrum of research topics, from basic science to clinical and outcomes research, were submitted for consideration. Of those, 14 were chosen for oral presentation.

The day kicked off with a keynote address from Dr. Adil Haider, Dean of Aga Khan University Medical College in Karachi, Pakistan and formerly of Johns Hopkins University and the Boston-based Center for Surgery and Public Health, a joint initiative between Harvard University and the Brigham and Women’s Hospital. He is regarded as one of the foremost experts on healthcare inequities in the United States, with projects focused on describing and mitigating unequal outcomes based on gender, race, sexual orientation, ethnicity, age and socioeconomic status. Dr. Haider spoke to the audience about his groundbreaking work in trauma disparities research, a field that he has helped establish by uncovering racial disparities after traumatic injury.

2019 Awards

Dr. Emily Steen was awarded the 2019 Samuel Stal Research Award. Over the past two years, Dr. Steen has been conducting basic science research in the Laboratory for Regenerative Tissue Repair under Dr. Sundeep Keswani, surgical director of basic science research at Texas Children’s Hospital. Dr. Steen’s work has focused on pediatric and fetal surgery, wound healing and fibrosis.

Texas Children’s Chief of Plastic Surgery Dr. Edward Buchanan received the 2019 Research Mentor Award. He was nominated by Dr. Kelly Schultz, a recent Baylor College of Medicine graduate.

“In addition to showing unparalleled commitment to his patients, Dr. Buchanan has been a strong mentor, sponsor and role model in clinical research throughout the entirety of my and many other students’ and residents’ medical careers,” said Schultz. “I’m grateful for the many hours Dr. Buchanan spent discussing research projects and imparting knowledge that would eventually pay off in the research I accomplished during medical school.”

Additionally, Dr. Yangyang Yu from Pediatric Surgery received the award for Best Poster, titled “Cost-Effectiveness Analysis of the Surgical Management of Infants Under 1 Year of Age with Feeding Difficulties.” And Dr. Candace Style won the award for Best Oral Presentation, titled “Citrulline Effectively Reduces the Rate and Severity of Necrotizing Enterocolitis Compared to Hydrogen Sulfide in the Premature Piglet Model.”

The event’s grand finale was the announcement of the 2019 Clayton Awards. This grant program, funded by the Department of Surgery, allows surgery researchers to generate the preliminary data necessary for National Institutes of Health (NIH) grant applications and other extramural funding. The recipients were:

Dr. Yi-Chun Liu, Otolaryngology
Evaluation of the benefit of bone conduction hearing device in children with unilateral congenital aural atresia

Michelle Roy, PA-C, Plastic Surgery
Cleft care instructional videos and their efficacy in postoperative outcomes

Dr. Guillermo Aldave, Neurosurgery
Pilot study of oncolytic adenovirus DNX-2401 for recurrent pediatric high grade tumors

Dr. Sarah Woodfield, Surgery
Profiling and modeling extracranial malignant rhabdoid tumors

The National Institute of Health awarded a team of Texas Children’s scientists a $2.2 million grant in 2018 to study and develop computer and tissue-engineered models to predict the recurrence of congenital heart diseases. The study aims to change the way heart diseases are managed to improve the quality of life of children. Learn more by visiting our 2018 virtual Annual Report.

February 11, 2019

The Clinical Research Center/Research Resources Office presented the Clinical Research Award for First Quarter 2019 to Ruth Eser-Jose, research coordinator with the Immunology, Allergy, Rheumatology and Retrovirology (IARR) Department.

This award was established by the Clinical Research Center in collaboration with the Research Resources Office to recognize and honor individual contributions to protecting the best interest of the research subjects and compliance with applicable rules and regulations.

Eser-Jose first joined Texas Children’s Hospital in 2005 and worked in the General Clinical Research Center (GCRC) as a staff nurse. She later transitioned in 2015 to her current role with IARR. Her research activities in the CRC focus on coordination and management of research participants in the Pediatric HIV/AIDS Cohort Study (PHACS) and International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) Cohort HIV studies.

October 29, 2018

Some of the brightest minds in neuroscience recently converged on the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital for its fourth biennial symposium and workshop, in partnership with Baylor College of Medicine.

The special two-day event brought together nearly 300 physicians, scientists, patients, patient advocacy groups, pharmaceutical industry experts and leaders from the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke, and the National Institute for Mental Health, to address key issues in the field of neuropsychiatry, an intersectional branch of medicine that deals with mental illnesses caused by organic disorders of the nervous system.

Neuropsychiatric disorders are a leading cause of disability and take a tremendous toll on society. In the United States alone, one out of five adults lives with mental illness. The spectrum of mental illnesses is vast, ranging from the extremely rare to more well-known conditions such as depression, anxiety, schizophrenia, ADHD, addiction and sleep disorders. Symptoms and their severity can vary widely from patient to patient, which makes them difficult to physiologically measure. For these reasons, neuropsychiatric disorders are some of the least understood – and some of the most difficult to treat.

“These disorders are a major health issue all over the world, however, therapeutic interventions remain limited,” said NRI/Baylor investigator and child neurologist Dr. Hsiao-Tuan Chao. “There is a growing need to understand the organic factors behind mental illness to facilitate a better understanding of the brain, as well as to develop more effective treatment strategies.”

The symposium opened with a welcome address from Dr. Huda Zoghbi, director of the NRI, and this year’s co-organizer, Dr. Steven Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard. The pair stressed the importance of identifying new research paths in order to develop targeted therapies that could not only help treat neuropsychiatric symptoms, but could also help mitigate or eliminate side effects and toxicities that far too many patients experience.

Over the course of the first day, presentations from leading experts addressed hot topics in neuropsychiatry. These included a discussion on how genetic mutations contribute to neuropsychiatric disorders; the involvement of neuronal networks in neuropsychiatric phenotypes; the impact of immune cells on these disorders; and a look into how adaptive deep brain stimulation could potentially help specific conditions. Each session gave way to a 20-minute moderated panel discussion on the topic at hand. This feature of the symposium is unique in that it leads to immediate discussion and active participation among the many different types of stakeholders present.

Following a day of stellar research presentations, the investigators split into three working groups that focused on Molecular Bases of Disease and Human studies, Circuits and Neuromodulation, and Young Investigators. The groups discussed not only everything they had heard over the course of the day, but also their vision for the next 20 years in neuropsychiatry, including the obstacles that currently exist and what is needed to overcome them.

The next morning, key points that had emerged from these discussions were shared with the audience. The working groups identified increased access to resources and funding as a major need. But unanimously, all of the young investigators noted the critical importance of building interdisciplinary, multi-institutional collaborations, with a focus on team science and data sharing.

“Building bridges between various disciplines aids in the identification of important areas of neuropsychiatry that require further investigation and therapeutic development,” said Chao. “Neuropsychiatry itself is an interdisciplinary field, and unraveling the causes for these conditions will require continued interdisciplinary collaborations to accelerate the pace of discovery.”

The proceedings will be published as a white paper in Science Translational Medicine, a leading weekly online journal and one of the event sponsors.

October 23, 2018

The New England Journal of Medicine (NEJM), one of the nation’s most respected peer-reviewed medical journals, has released a new study highlighting the groundbreaking work being done by the Undiagnosed Diseases Network (UDN), an National Institutes of Health-funded research consortium that includes the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital, Baylor College of Medicine, Stanford University and other institutions.

Identifying the genes responsible for rare or unknown disorders using traditional approaches is time-consuming work and can take years, or sometimes even decades. And though genetic sequencing is now a routine part of the care people receive for these types of disorders, many patients are still left without a diagnosis. According to the NEJM study, the collaborative UDN model may already be changing that paradigm.

The study reports that the UDN defined 31 entirely new syndromes, and of 382 completed evaluations, 132 patients received diagnoses, a rate of 35 percent – all in just 20 months. The study also found that of the new diagnoses, 37 percent led to non-therapeutic changes in care, such as narrowing of diagnostic testing, and an amazing 21 percent led to changes in therapies for patients.

“This is a major accomplishment in genomic medicine and a giant step forward for these patients and their families,” said Dr. Huda Zoghbi, director of the NRI.

The UDN was established in 2014 with the mission of providing answers for the millions of patients and their families affected by mysterious and rare conditions, but who, after years of extensive testing, still hadn’t received a diagnosis.

The NRI and Baylor have been at the forefront of discovery in the UDN since its inception, jointly serving as one of seven original clinical sites, where doctors and health care providers, ranging from neurologists, immunologists, nephrologists, endocrinologists and geneticists, come together to help find the cause of participants’ symptoms. Baylor, one of the UDN’s two original sequencing cores, currently acts as the network’s sole DNA sequencing site. The NRI and Baylor were also selected to serve as the UDN’s first Model Organism Screening Center (MOSC), which was spearheaded by NRI investigators Drs. Hugo Bellen, Shinya Yamamoto and Michael Wangler.

“The UDN recognized that the resources we had in place and our high throughput made us the ideal candidate to serve as a MOSC site,” Bellen said. “Because of our success with model organisms and the appreciation physicians have for our work, there will likely be a proliferation of MOSC sites in the future.”

In-depth fruit fly studies at the MOSC have helped physicians and scientists identify genes responsible for rare and undiagnosed disorders, leading to the diagnosis of some of the UDN’s most difficult cases. This collaborative effort, which also includes the University of Oregon, has already directly influenced how clinicians care for patients – patients like Avery Reilly.

At only a few months old, Avery began showing signs of a neurologic condition. She could not sit until age 3 or crawl until age 5, and today she cannot walk or speak. An appointment with Texas Children’s neurologist Dr. Timothy Lotze revealed Avery had poor muscle tone, which was delaying milestones. That initial appointment led to years of doctor visits and countless tests, all of which failed to reveal the cause of Avery’s developmental and speech delays.

Then in 2014, the Reillys heard about the NRI’s involvement with the UDN and submitted Avery’s case. For the first time in years, the family had hope. Using exome sequencing, researchers discovered Avery had a new type of genetic mutation. Then a team at the MOSC, led by Wangler, studied the mutation in a fruit fly model to see how the genes were affected. At long last, the Reillys had a diagnosis. What’s more, the discovery of Avery’s mutation led to a change in her medications, which could help slow the progression of her disease.

“The fact that we are able to help the UDN accelerate science to find actionable changes in therapies is very exciting,” said Zoghbi. “Helping people, and working to solve severe medical problems through basic research, and through unfettered collaboration, is what our work is all about.”

The NEJM study is the first to provide a detailed description of the inner workings of the UDN. It presents an in-depth analysis of the referral and acceptance patterns, diagnoses, impact rates and follow-up scientific investigations of 1,519 cases that were referred to the UDN in the last two years.

As the study points out, the most unique feature, and perhaps the biggest contributor toward UDN’s success, is its model of multi-institutional collaborations. Teams of researchers and physicians from participating institutions all over the nation leverage their multidisciplinary expertise and resources to quickly find specific diagnoses for patients with extremely challenging clinical cases, with no additional cost to the patients.

In addition to the original clinical sites and sequencing cores, the UDN also included a coordinating center as part of its phase I deployment. In 2015, a web-based portal, the UDN Gateway, was launched for patients and families to participate in UDN. The network recently expanded its footprint from seven to 12 clinical sites and also added a central biorepository, a metabolomics core and a new MOSC site.

Though the UDN’s larger focus is currently gene discovery, it’s the work being done at the NRI and Baylor that will set up the network’s next evolution.

“Once a gene is discovered, it’s natural that the focus should shift to finding out what the genes do, what the molecular mechanisms are, if they’re linked to other diseases, or if they can be manipulated with drugs,” Bellen said. “That’s what we’re doing at the NRI and Baylor now, and that will be instrumental in the next phase for the UDN. When that time comes, we’ll be ahead of the curve.”

Learn more about the recent research breakthroughs and patient success stories from the UDN and MOSC.

About the New England Journal of Medicine
For over 200 years, the New England Journal of Medicine has rigorously vetted and compiled the latest medical research in support of physicians and their patients. From the first uses of anesthesia to the most recent cardiology and cancer treatments, the New England Journal of Medicine has helped generations of clinicians enhance their knowledge and improve patient care.

Today, with rigorously peer-reviewed research, topical reviews, interactive clinical content and cases, the New England Journal of Medicine is the trusted source for essential findings in medicine.

October 15, 2018

The Clinical Research Center/Research Resources Office presented the Clinical Research Award for Third Quarter 2018 to Ananth Iyer, Project Manager, Quality Assurance/Quality Control, Department of Pediatrics – Research Resources Office.

This award was established by the Clinical Research Center in collaboration with the Research Resources Office to recognize and honor individual contributions to protecting the best interest of the research subjects and compliance with applicable rules and regulations.

“I joined the Research Resources Office (RRO) in 2014 as a Senior Research Coordinator and am currently in a Quality Assurance (QA) role,” said Iyer. “I take pride in providing support for good quality and compliance in the clinical trials that we undertake. I’m highly motivated by the care and options that clinical research studies provide to patients and never forget that their safety and protection is our top priority. I enjoy the teamwork with which clinical care and research come together in the RRO and I deeply appreciate the RRO for providing me (a lifelong student) with this opportunity.”

September 4, 2018

The Southwest Pediatric Device Consortium (SWPDC), anchored at Texas Children’s Hospital and Baylor College of Medicine, recently received a prestigious P50 grant from the U.S. Food and Drug Administration. The five-year, $6.75 million grant will begin on September 1 and will allow SWPDC to leverage ongoing activities to expand and accelerate the development of much-needed pediatric medical devices. The five principal investigators include Drs. Chester Koh and Henri Justino of Texas Children’s and Baylor, Dr. Balakrishna Haridas of Texas A&M University, Dr. Maria Oden of Rice University, and Dr. Michael Heffernan of Fannin Innovation Studio.

SWPDC supports pediatric device innovators with the goal of addressing the shortage of needed novel medical devices for children, a public health problem that has been acknowledged by the FDA.

“A great need currently exists for medical devices designed specifically for children,” said Koh, founder of SWPDC and lead principal investigator, as well as a pediatric urologist at Texas Children’s and professor of urology, pediatrics and Ob/Gyn at Baylor. “Pediatric device development is challenging, but with this support from the FDA, our consortium will continue to assist pediatric device innovators along all stages of development with the goal of improving our care of pediatric patients.”

The past decade has been a period of growth in adult medical device innovation. Advances in devices for children, however, have lagged far behind. Why the disparity? Economics are partially to blame. The market for pediatric devices is smaller, and thus the return on investment lower. Then there are the clinical and regulatory challenges. Pediatric device projects may need an extended life cycle before they can be approved and exposed to the external market. As a result, pediatric surgeons and pediatricians have had to make do with what’s available, often using retooled adult medical devices, and without adequate testing in children.

“Significant technical (design and manufacturing), preclinical testing, clinical and regulatory testing challenges exist in the field of pediatric devices,” said Haridas, co-founder and co-PI of SWPDC (lead PI at Texas A&M) and professor of practice in biomedical engineering at Texas A&M. “This FDA-funded SWPDC is uniquely positioned to address these challenges across the pediatric device development and clinical translational cycle to deliver significant advances in treatments tailored for pediatric patients.”

Support from the P50 grant will enable SWPDC to provide services in several areas: unmet needs assessment, prototype development, product and technology acceleration services, and business acceleration services. Consortium members will evaluate and support projects, as well as advise innovators throughout the total product life cycle. Based on individual project needs, the consortium will direct investigators to specific resources, collaborators and industry experts, and will coordinate the services offered by its member programs to identify, evaluate and assist pediatric device projects.

SWPDC includes clinical, scientific/engineering, investment, regulatory and academic partners in the Texas Medical Center, the Greater Houston area and the southwestern U.S. Primary partners include Texas A&M University, Rice University, University of Houston and Fannin Innovation Studio, and includes others such as Biotex Inc., Children’s Hospital of San Antonio, Children’s Health in Dallas and Phoenix Children’s Hospital, with additional future sites. SWPDC was selected as one of five national consortia that are addressing the shortage of pediatric devices.

To learn more about the Southwest Pediatric Device Consortium, visit swpdc.org.