In addition to our regular CRI Activities Update, this month’s Research Focus highlights collaborative work from the team led by Matthew Laughon, MD, MPH, Professor of Pediatrics in the division of Neonatal-Perinatal Medicine.

Activities Update:  The latest news announcement on the Mary Ellen Jones building renovation can be found here. The renovation schedule remains on track for labs to begin occupancy in the spring of 2019.

We are excited to announce that two new researchers are joining our department and the CRI.  Haiyan Fu, PhD will be joining us from Nationwide Children’s Hospital. Her long-standing collaboration with Joseph Muenzer, MD, PhD in the translational science of gene therapy for Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, led to the December 2017 FDA approval for an Investigational New Drug (IND) application to proceed with gene therapy clinical trials in Hunter syndrome patients.

James Hagood, MD will be joining us from the University of California, San Diego. His research using animal models to study the molecular regulation of fibroblast phenotypes in pulmonary fibrotic disease and lung alveolarization has shown that, contrary to the long-held perception that fibrotic tissue is permanent, organ fibrosis can be highly malleable and even regress under the proper conditions. This gives rise to the potential for new effective restorative therapies in the treatment of pulmonary fibrosis.

We are also excited to share that Michael Kappelman, MD, MPH will serve as the Lead Scientific PI for the Crohn’s & Colitis Foundation “Comparative Effectiveness of Biologic or Small Molecule Therapies after Failure of Anti-TNF Treatment in Patients with Crohn’s Disease and Ulcerative Colitis,” funded by the Patient-Centered Outcomes Research Institute (PCORI). Studies will use PCORnet, the National Patient-Centered Clinical Research Network, to test ways to improve care for people with arthritis, blood pressure, depression and irritable bowel disease.

Finally, UNC, in collaboration with Duke University, re-submitted the Unified Program for Therapeutics in Children (UPTiC) T32, lead and written by Ian Davis, MD, PhD at UNC and Sallie Permar, MD, PhD at Duke. UPTiC aims to develop a comprehensive program that rigorously trains pediatric physician-scientists in the development and testing of therapeutics by creating a strong cross-institutional mentorship network for pediatrician-scientists and providing a broad range of training opportunities. This collaborative submission addresses the need to develop and test treatments specific to children. A study of over 355,000 hospitalized children showed that close to 80% of the pharmacological treatments used were off-label. Children are often referred to as “therapeutic orphans” and do not share the same benefits of the novel therapeutics pipeline as adults. The NIH review will take place this fall.

Reminder: Matthew Laughon, MD, MPH is presenting “Sildenafil in Premature Infants” at our next CRI monthly luncheon seminar series. The event will be held on Tuesday, June 12 from 12:15-1:30pm in the Bioinformatics Auditorium (room 1131). Please mark your calendars. We look forward to seeing you there.

Research Focus of the MonthThis month, we are excited to feature the research of Matthew Laughon, MD, MPH, Professor of Pediatrics in the division of Neonatal-Perinatal Medicine.

Matthew Laughon, MD, MPH
Matthew Laughon, MD, MPH

Pediatric clinical trials are largely underrepresented in pharmacological research, particularly those that focus on premature infants, resulting in prescribing medications off-label when treating this population. This is a challenge because children respond differently to treatments than adults because of differences in metabolism and immune development, resulting in increased morbidity and even mortality when using drugs off-label in children. Matthew Laughon, MD, MPH, and his colleagues are working to address this lack of pediatric clinical trial data through their research on the efficacy of therapeutic medications given to premature infants with postnatal complications, such as bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA).

BPD is the most common pulmonary cause of morbidity in premature infants and can cause many complications throughout life. Dr. Laughon is working on a phase II trial of sildenafil in the treatment of premature infants diagnosed with BPD. Sildenafil is one of the most common medications given to treat BPD; however, it currently has limited clinical trial data to support its use in children and carries a black box warning from the FDA against chronic use in children. This puts clinicians in the situation of prescribing a treatment with doubts, having to weigh the risks and benefits. Dr. Laughon is also studying the safety of preventative furosemide in premature infants at risk for BPD in research funded by the FDA. In addition, he participates in and oversees a variety of multi-center studies as Protocol Chair and satellite PI within the Pediatric Trials Network and the Neonatal Research Network, which are funded through the Eunice Kennedy Shriver National Institute of Child Health and Human Development. These collaborations are carried out in conjunction with colleagues Danny Benjamin Jr, MD and Michael Cotten, MD at the study’s principal site, Duke University. Dr. Laughon is also collaborating with Brian Smith, MD, who serves as PI for Duke University’s ECHO Coordinating Center, funded by the National Institutes of Health’s Office of the Director.

Links to more information about Dr. Laughon, his work and a selection of publications and sources are listed below.

http://www.pediatrictrials.org/
https://neonatal.rti.org/

Thakkar N, Gonzalez D, Cohen-Wolkowiez M, Massaro MM, Bernhardt J, Zane NR, Laughon MM. An opportunistic study evaluating pharmacokinetics of sildenafil for the treatment of pulmonary hypertension in infants. J Perinatology. 2016 Sep;36(9):744-7. doi: 10.1038/jp.2016.79. Epub 2016 May 12. PMID: 27171763

Laughon MM, Benjamin DK Jr. Mechanisms to provide safe and effective drugs for children. 2014. Pediatrics;134(2):e562-3.

Beam KS, Aliaga S, Ahlfeld SK, Cohen-Wolkowiez M, Smith PB, Laughon MM. A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants. J Perinatol. 2014 Sep;34(9):705-10. doi: 10.1038/jp.2014.126. Epub 2014 Jul 10. PMID: 25010224

Jackson W, Hornik CP, Messina JA, Guglielmo K, Watwe A, Delancy G, Valdez A, MacArthur T, Peter-Wohl S, Smith PB, Tolia VN, Laughon MM. In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia. J Perinatol. 2017 Apr 6.

Perez KM, Laughon M. Sildenafil in Term and Premature Infants: A Systematic Review. Clin Ther. 2015 Nov 1;37(11):2598-2607.e1.