Significant Accomplishments

Progress Against Pediatric Lung Disease

Kathryn Wikenheiser-Brokamp, MD, PhD, studies the genetic and developmental basis of lung disease, with specific interest in the pediatric lung tumor pleuropulmonary blastoma (PPB), chronic obstructive pulmonary disease and lung cancer. Wikenheiser-Brokamp has identified critical biologic functions for the Rb/p16 and p53 pathways in pulmonary epithelial progenitor/stem cell growth in the context of lung development, repair after injury and carcinogenesis.

Wikenheiser-Brokamp also studies how DICER1 and the microRNAs it generates control organogenesis and protect against PPB. She leads the basic science research for a multi-institutional team of researchers that recently discovered the first human syndrome associated with DICER1 mutations. She also serves as principal investigator on a consortium grant to explore the key regulatory pathways underlying DICER1 related lung phenotypes.

Wikenheiser-Brokamp has developed mouse models based upon genetic alterations in human disease along with complementary cell culture systems to identify key regulatory networks controlling lung development and disease pathogenesis. Her research is supported by the NIH, American Cancer Society, and the St. Baldrick’s Foundation. This year, Wikenheiser-Brokamp also was appointed Associate Director of the Medical Scientist (MD/PhD) Training Program.

Breakthrough Findings in Pediatric Liver Disease

Since joining the Department of Pediatrics in 1984, Kenneth Setchell, PhD, has focused his work in bile acid metabolism. He has identified and described six genetic defects in the pathway for bile acid synthesis, which are manifested as progressive neonatal liver disease. His research group now serves as an international center for the diagnosis and treatment of liver disease caused by genetic defects in cholesterol and bile acid syntheses.

In a recent study published in Gastroenterology, Setchell and colleagues characterized the clinical, biochemical, molecular and morphologic features of a genetic defect in bile acid conjugation in 10 pediatric patients with fat soluble vitamin deficiency, and some patients with growth failure or transient neonatal cholestatic liver disease. Their findings reveal the importance of bile acid conjugation in lipid absorption and indicate that patients with idiopathic neonatal cholestasis or later onset of unexplained fat soluble vitamin deficiency should be screened for defects in bile acid conjugation.

This study has been recognized in multiple published commentaries due to the significance of these observations, which may represent only the tip of an iceberg of patients with hereditary defects in bile acid conjugation.

Mass Spectrometry Expands

We have invested heavily in expanding our mass spectroscopy capabilities,  including increased technical support and state-of-the-art equipment. We now operate 10 mass spectrometers ranging from simple quadrupole mass specs to highly accurate triple quadrupole time-of-flight equipment that will be the cornerstone of our developing metabolomics program.

Currently, our mass spectrometry labs perform more than 17,000 clinical assays a year. We also are working to develop and implement a personalized therapy drug management program in collaboration with colleagues in Clinical Pharmacology and Pathology and Laboratory Medicine.

Neuropathology Program Grows

Brain tumors are the leading cause of childhood cancer deaths. Pediatric brain tumors are recognized as being biologically different from adult tumors and require a different treatment approach. Cincinnati Children’s has become a nationally recognized center for treating childhood brain tumors, evaluating approximately 100 new brain tumor cases a year.

Lili Miles, MD, who joined our Division in 2003, brings special expertise in pediatric neuropathology and muscle disorders to the battle against pediatric brain tumors. She has worked closely with a clinical team including members of Neuro-Oncology, Neurology, Neurosurgery, and Radiology to develop the brain tumor program at Cincinnati Children’s. Miles also provides pathology review expertise for the Diffuse Intrinsic Pontine Glioma International Repository, which is based at Cincinnati Children’s and supported by funds from The Cure Starts Now Foundation. Miles recently presented a review of the tumor repository and ongoing studies at a Foundation-sponsored symposium in Cincinnati.

Cincinnati Children’s also is the primary site for the national Pediatric Brain Tumor Consortium under the direction of Maryam Fouladi, MD. In the Consortium’s medulloblastoma protocol study, Miles will be providing state-of-the-art pathology support to characterize potential biological markers that could enhance the classification of these tumors and potentially serve as targets for improved therapy.