Dr. Trittmann is Assistant Professor in the Division of Neonatology, Department of Pediatrics at The Ohio State University College of Medicine and Principal Investigator in the Center for Perinatal Research at The Research Institute at Nationwide Children’s Hospital. Dr. Trittmann’s research focuses on bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH), a life-threatening neonatal disease characterized by progressive pulmonary vascular endothelial dysfunction and smooth muscle cell proliferation. Currently, there are no available predictive biomarkers or curative therapies for BPD-PH. Our labs at The Research Institute have discovered three potential biomarkers for BPD-PH: arginase-1 (ARG1), asymmetric dimethylarginine (ADMA), and NᴳNᴳ-dimethylaminohydrolase-1 (DDAH1), that are differentially expressed in neonatal patients with BPD-PH versus BPD alone. Therefore, Dr. Trittmann’s work focuses on (1) further development of ARG1, ADMA, and DDAH1 as clinical biomarkers for BPD-PH and (2) the mechanism of action of ARG1, ADMA, and DDAH1 as it relates to BPD-PH pathogenesis. The overall goal is to precisely target treatment to improve outcomes for neonatal patients with BPD-PH.

Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth, and one of the leading causes of pediatric chronic lung disease. There are approximately 14,000 new cases of BPD diagnosed each year in the United States. Pulmonary hypertension (PH) complicates the clinical course in approximately 25-40% of BPD patients and is the greatest contributor to morbidity and mortality in BPD. PH is characterized by increased pulmonary vascular resistance caused by decreased vessel diameter as a result of vasoconstriction and/or vascular remodeling. Nitric oxide (NO) metabolism has been found to be altered in patients with severe BPD. NO, an endogenous pulmonary vasodilator, is produced by NO synthase (NOS) from L-arginine in pulmonary endothelial cells. L-arginine can also be metabolized by arginase to form ornithine and urea, and this is the first step in polyamine and proline synthesis that is necessary for the cell proliferation underlying vascular remodeling. Our group has shown that NO production can be influenced by the bioavailability of L-arginine to NOS either by alterations in cellular uptake of L-arginine or by metabolism by arginase. Furthermore, a product of protein methylation, ADMA, inhibits NOS production of NO and promotes vasoconstriction and proliferation. ADMA is degraded in the cell by dimethylarginine dimethylaminohydrolase (DDAH). These cell studies combined with patient sample data that demonstrate the differential expression of ARG1, ADMA, and DDAH1 in neonatal patients with BPD-PH versus BPD alone, provide a foundation of evidence to further develop arginase, ADMA, and DDAH as clinical biomarkers and therapeutic targets to improve outcomes for neonates with BPD-PH.