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Pediatric Research Newsletter

March 2016

Respiratory Pathogens Research Center

By Samreen Jatana

Mary Caserta

Mary T. Caserta, M.D.

Mary T. Caserta, M.D., George Washington Goler Professor of Pediatrics at the University of Rochester, is currently collaborating with a large group of physicians and scientists on studies that are part of the Respiratory Pathogens Research Center. The center is funded by the National Institute of Allergy and Infectious Diseases and is led by Drs. David Topham and Ann Falsey. Dr. Caserta is the director of the Pediatric Clinical Core and devotes much of her energy to two main studies.

Current Studies

Mechanisms Affecting RSV Disease Severity in Infancy
The first study aims to examine the biological factors associated with Respiratory Syncytial Virus (RSV) disease severity in otherwise healthy infants and brings together investigators Dr. Thomas J. Mariani from Pediatrics, Dr. Edward E. Walsh from Medicine, Dr. Steven R. Gill from Microbiology and Immunology, and Dr. David Topham from the Center for Vaccine Biology and Immunology. For the past three winters, the researchers collected samples from infants with RSV infection in both hospital and ambulatory settings, and they are now completing laboratory assays and analyzing data. By comparing subjects with mild disease to those with severe disease, the team hopes to glean insights into the mechanisms that affect RSV disease severity in infancy.

Longitudinal Evaluation of Immune System Development
In the second study, Dr. Caserta collaborates with Gloria S. Pryhuber, M.D., a member of the division of Neonatology, on a longitudinal evaluation of immune system development, respiratory infections, and the risk of wheezing and other respiratory disease in children following preterm birth. They have enrolled more than 200 children in the study and will follow them over the first three years of life. The study is expected to provide a rich source of data to help answer important questions about immune system development in both term and preterm infants as well as about the impact of the immune response on respiratory outcomes later in life.

Recently Published Studies

Can Parent-Child Relationships Affect Children's Antibody Response to Vaccination?
In a separate collaborative effort with several faculty members in the Department of Psychiatry including Drs. Thomas G. O’Connor, Jan A. Moynihan, and Peter A. Wyman, Dr. Caserta studied the link between psychosocial stress, the immune response, and susceptibility to infectious diseases in children. Studies evaluating over 350 children between the ages of 5-13 years at Golisano’s Children Hospital have led to several publications that showed that chronic stress in the family modulated the function of natural killer cells, an integral part of the innate immune system of the body. In addition a recent article by Dr. Caserta and her collaborators examined how parent-child relationships can affect antibody response to vaccination in children. They measured antibody responses to meningococcal conjugate vaccine in a group of 164 children aged 10-11 years. They also observed the parent-child relationship in a problem-solving task and correlated the quality of this interaction with vaccine response. Interestingly, they found a negative interaction between the parent and child predicted a less robust response to the vaccination. This observation is important from a public health perspective because it suggests that parent-child conflict and exposure to stress may lead to altered immune system development in children.

What is the Effect of Valganciclovir Therapy in Neonates with CMV disease?
Dr. Caserta is also a member of the Collaborative Antiviral Study Group (CASG), which is coordinated by the University of Alabama at Birmingham and funded by the NIAID. CASG coordinates multi-center clinical trials of anti-viral medications for the treatment of uncommon viral diseases. The most recently completed study, which included 40 centers, examined the effect of valganciclovir therapy in neonates with symptomatic congenital cytomegalovirus (CMV) disease. CMV infection can cause hearing loss and neurodevelopmental deficits in neonates. The standard treatment of newborns exhibiting CMV disease symptoms is intravenous therapy with ganciclovir or oral administration of valganciclovir. The new study showed that treatment with valganciclovir for an extended time period of 6 months, compared with 6 weeks, improved long-term hearing outcomes in the infants at 12 and 24 months of age.

Pediatric Gastroenterologist Participates in International FDA Study

By Rachel Bills 

Rebecca Abell

Rebecca L. Abell, D.O.,
Assistant Professor
of Pediatrics, Division of
Gastroenterology / Nutrition

Inflammatory bowel disease (IBD), including ulcerative colitis, affects an estimated 100,000 children in the United States, with a large population being treated at Golisano Children’s Hospital each year. The human anti-TNF-α monoclonal antibody adalimumab, commonly known as Humira®, has shown promise as an effective treatment for IBD. As is the case for most medications, the evaluation and approval of this medication has lagged behind its application to adult patients. Recently, adalimumab has been approved by the FDA for use in children under 18. Despite this, more needs to be learned about the optimal dosing of adalimumab in the pediatric population. Therefore, the FDA has initiated an international clinical trial to further study the use adalimumab in children under 18 with moderate-to-severe ulcerative colitis.

Golisano Children’s Hospital was recently selected as one of the 70 international sites to participate in this study, which should play a key role in establishing future pediatric guidelines for the safe and effective use of this medication. Other institutions participating include Massachusetts General Hospital, University of Chicago, and Indiana University Health. Rebecca L. Abell, D.O., Assistant Professor of Pediatrics in the Division of Gastroenterology/Nutrition, is spearheading the effort at the University of Rochester.

The trial is a randomized double-blind, placebo-controlled, 52-week study with an ultimate goal of 225 subjects, ages 4-17 years. Dr. Abell is currently working with study coordinator, Barbara Johnson, RN, on the screening and enrollment process at the University of Rochester.

Still very much in the early stages and as is typical for studies with relatively uncommon conditions in children, it is anticipated that it will take a couple of years to gather data and analyze the results. According to Dr. Abell, Humira is currently being used in children with favorable outcomes; however, this study will provide the FDA with further information on the safest and most effective dosing for the pediatric population. If this trial is successful, it will provide a more efficacious treatment to alleviate the symptoms of ulcerative colitis, as well as improve the course of the disease, possibly preventing the need for future surgeries or other complications.

Pediatric Fellow Granted Young Investigator’s Award for Research with Developing Heart

By Meghan Plog

Jayson Lingan, M.D., third year Neonatology fellow, was recently awarded the Pediatric Clausen Fellowship in recognition of his research investigating the role of the mitochondrial permeability transition pore (mPTP) in the maturation of cardiac myocytes. Because the human heart’s capacity for regeneration decreases soon after birth to a state of very slow cardiac muscle cell replacement, therapy for congestive heart failure is extremely difficult. However, recent studies from the lab of Lingan’s mentor, George A. Porter, M.D., Ph.D., have suggested a potential new therapy that will enhance cardiac myocyte differentiation and thus promote the maturation of the heart muscle. Preliminary findings in an embryonic mouse model have revealed that closure of the mPTP is found to do just that. Lingan is currently working to prove this same hypothesis in a neonatal mouse model, operating under the notion that embryonic and neonatal hearts share a similar structure. Through in-vitro and in-vivo testing, they are asking the question: “Will the closure of the mPTP in neonatal hearts push the heart to mature faster, and in the process of maturation, improve function?” If so, there is great potential for clinical application.

Award

Program Director, Dr. Patty Chess,
Dr. Jayson Lignan and his mentor,
Dr. George Porter

In today’s treatment of neonatal congestive heart failure, the current therapies being used are mostly temporizing and primarily based on anecdotal evidence or expert opinion. Through preliminary testing, the Porter lab has identified a possible new therapy. They have found that both Cyclosporin A (CsA) and NIM811, a non-immunosuppressive analogue of CsA, cause the mPTP to close, and thus the heart muscle differentiates earlier. While preliminary findings have shown these agents work in cells, Lingan’s recent experiments measuring cardiac function using echocardiography suggest that closure of the mPTP does indeed improve cardiac function in vivo. If these findings are substantiated, then these medications could potentially serve as a new therapy for congestive heart failure in infants or for those recovering from cardiac surgery.

Lingan was recently among 30 fellows and junior faculty across the country invited to present their research at the 2nd Annual Neonatal Cardiopulmonary Biology for Young Investigator’s Forum in Chicago, IL. He had the unique opportunity to present to key leaders in the field of neonatology and was ultimately selected as one of only eight finalists for a grant to support the continuation of his work. Lingan feels honored to have received this award and credits the continuous support of his mentor, Dr. George Porter.

Research Publication Highlights

2016 - 1st Quarter