Reducing Pathological Inflammation after Neonatal Intraventricular Hemorrhage

Title: Reducing Pathological Inflammation after Neonatal Intraventricular Hemorrhage Candidate''s interests, background, and goals: I am a pediatric neurosurgeon in my third year of clinical practice. My appointment at the University of Kentucky (UKY) includes 50% protected research time. This position is based on my clinical and research experience, which has been the culmination of my education and training for over twenty years. While an undergraduate at Washington University in St. Louis (WashU), I was a member of the laboratory of Dr. T.S. Park, one of the most experienced pediatric neurosurgeons in the United States. During that time, I learned animal surgical skills, histological analysis, and began to understand the biology of brain injury after ischemia and hypoxia. The framework for this understanding came largely from interactions with Dr. Jeffrey Gidday who directed the laboratory and provided me with one-on-one mentorship. My undergraduate work culminated with a first author publication demonstrating that hypoxic preconditioning can protect the brain against ischemia. This publication has been cited over 150 times. I obtained my MD and PhD from The Ohio State University, where my research focused on oligodendrocyte progenitor cell biology in the context of spinal cord injury. I was mentored by Dr. Michael Beattie and Dr. Jacqueline Bresnahan, two of the most influential spinal cord injury scientists in the world. Their laboratory has made seminal contributions to the understanding of inflammation and apoptosis after spinal cord injury. During my training, the laboratory moved to University of California San Francisco’s Department of Neurological Surgery. There, I interacted with several successful neurosurgeon-scientists who became models for my career. During graduate school, I was awarded an F30 Fellowship from the NIH, which supported both my graduate and clinical training. During my residency, I conducted research on the role of inflammation in brain injury after subarachnoid hemorrhage. This work was funded by three grants I received, including an NIH R25 fellowship. My fellowship project focused on inflammation after subarachnoid hemorrhage and gave me the opportunity to learn new laboratory techniques including new animal surgical models and real-time PCR. Near the end of residency, I spent one month at St. Louis Children’s Hospital and WashU, sponsored by an award from the AANS Joint Section on Pediatric Neurosurgery. This led me to choose St. Louis Children’s Hospital for my pediatric neurosurgery fellowship. As a fellow at WashU, I worked with Dr. Stuart Friess and Dr. David Brody, both clinician-scientists, examining oligodendrocyte progenitor cell fate in a pediatric traumatic brain injury model. While I have a long-standing interest in neurotrauma, my clinical practice in pediatric neurosurgery has driven my research interest towards neonatal intraventricular hemorrhage and post-hemorrhagic hydrocephalus (IVH/PHH). This is a common condition treated by pediatric neurosurgeons, but there are no guidelines on when to surgically intervene, and no pharmacologic therapies. Because of my neurotrauma research experience, I was well acquainted with the Spinal Cord & Brain Injury Research Center (SCoBIRC) at University of Kentucky (UKY), one of the premier neurotrauma research groups in North America. The SCoBIRC faculty provide numerous collaboration and mentorship opportunities and have expertise in multiple techniques that are incorporated into my work. Both Dr. Hall, who was the first permanent Director of SCoBIRC from 2002-2012, and Dr. Gensel, who was Dr. Hall’s last recruit as SCoBIRC Director, are mentors and collaborators of mine. Dr. Gensel was a graduate school colleague of mine and was also mentored by Dr. Hall during his recent promotion to tenure. My long-term goal is to advance the field of pediatric neurosurgery, by improving the treatment of IVH/PHH. I plan to develop clinical trials in both pharmacologic interventions and surgical technique (e.g., timing of surgical intervention for IVH-induced hydrocephalus) that will improve patient outcomes. This long-term goal is supported by my current laboratory work, using in vivo and in vitro techniques to study how IVH/PHH induces inflammation within the brain and if anti-inflammatory treatments can improve outcomes. My short-term goals are to: 1. Establish my research focus by developing a preclinical model of neonatal IVH/PHH, and testing pharmacological approaches to treat IVH/PHH. 2. Improve my neuroimmunology knowledge to bring a sophisticated analysis of neuroimmunology to the field of neonatal IVH. 3. Develop my skills in translational science to ultimately move my basic science discoveries in to clinical trials. Advancing my own laboratory work and translational research experience will allow me to improve treatment for children with IVH/PHH and move past the primitive concepts that guide our current management of these patients. Rather than just rely on surgery to treat PHH, I hope to develop therapies that treat the underlying cause of brain injury in IVH/PHH.