My research efforts are focused on finding cures for children with brain tumors and cerebrovascular disease. I am committed to building bridges between clinical practice and scientific research in order to leverage the unique perspective of a surgeon-scientist. The disorders that I treat—brain tumors and cerebrovascular disease—are linked by similar operative approaches that I use in the hospital and by common biological processes that I study in the lab.
My research is primarily centered on understanding the molecular mechanisms of tumorigenesis and angiogenesis in the central nervous system, in conjunction with efforts of the Vascular Biology Program, led by Dr. Marsha Moses. My work has included basic science and translational studies investigating adult and pediatric brain tumors, moyamoya disease and cerebral arteriovenous malformations. In particular, my laboratory—with colleagues—has discovered novel biomarkers for neurosurgical disease and has studied a class of molecules that markedly influence the malginant nature of tumors and the capacity of blood vessels to grow in the brain. This research has direct impact on brain tumors, moyamoya and arteriovenous malformations.
In particular, I am interested in the development of tests to better screen for the presence, recurrence and progression of brain tumors and cerebrovascular disease using non-invasive biomarkers. My laboratory published the first report describing the successful use of urinary biomarkers to identify brain tumors and has since expanded this work to include—for the first time—the ability of urinary biomarkers to predict therapeutic efficacy in cerebrovascular disease.
This research, supported by the NIH and national foundations, serves as the core of an ongoing five-year national multicenter trial to study brain tumor recurrence and directly complements our mechanistic studies of brain tumor invasion conducted in the Vascular Biology Program. Together, this work has led to the current development of novel therapeutic agents now being studied in our lab.
Our comprehensive patient database, representing the largest experience with pediatric cerebrovascular disease in the world, provides rich source material for ongoing studies. The database allows us to track long-term patient outcomes, compare the results of different surgical and neurointerventional procedures, evaluate newly adopted interventions and improve our quality of care.
My clinical expertise has led to authoring a number of important guidelines and articles about these conditions, including the American Heart Association Guidelines for the Management of Cerebrovascular Disorders in Infants and Children, a New England Journal of Medicine paper on moyamoya disease, and some of the largest studies published on arteriovenous malformations, cavernous malformations and pediatric aneurysms.
The special environment of Boston Children’s Hospital—combining world-class clinical care with internationally renowned scientists—has enabled remarkable advances in the science and treatment of pediatric disease. Our lab has been fortunate to contribute to these efforts and we continue to work as hard as we can to pave the way for new treatments. Some of the foundation from our lab for exciting future work includes:
Smith ER, Manfredi M, Scott RM, Black PM, Moses MA. A recurrent craniopharyngioma illustrates the potential usefulness of urinary matrix metalloproteinases as noninvasive biomarkers: case report. Neurosurgery 2007 Jun; 60(6):E1148-9; discussion E1149.
Smith ER, Zurakowski D, Saad A, Scott RM, Moses MA. Urinary biomarkers predict brain tumor presence and response to therapy. Clin Cancer Res 2008 Apr 15; 14(8):2378-86.
Roach ES (Chair), Golomb M, Adams R, Biller, Daniels JS, deVeber G, Ferriero D, Ichord R, Jones B, Kirkham F, Scott RM, Smith ER. Guidelines for the management of cerebrovascular disorders in infants and children: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 2008 Jul 17; 39(9): 2644-91.
Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009 Mar 19; 360(12):1226-37.
Smith ER, McClain CD, Heeney M, Scott RM. Pial synangiosis in patients with moyamoya syndrome and sickle cell anemia: perioperative management and surgical outcome. Neurosurgery Focus 2009 Apr;26(4):E10.
Gross BA, Scott RM, Smith ER, Management of Brain Arteriovenous Malformations, Lancet, 2014, May 383(9929):1635
Akino T, Han X, Nakayama H, McNeish B, Zurakowski D, Mammoto A, Klagsbrun M, Smith ER, Netrin-1 promotes medulloblastoma cell invasiveness and angiogenesis, and demonstrates elevated expression in tumor tissue and urine of pediatric medulloblastoma patients, Cancer Research 2014 Jul 15;74(14):3716-26
Orbach D, Storey A, Morash D, Estroff J, Smith E, Trenor C, Olson H, Pathogenesis of dural sinus malformations as demonstrated by fetal imaging: a decision-making crucible for parents and clinicians. Journal of Neurointerventional Surgery, 2014 Jul;6 Suppl 1:A69-70.
Weinstock P, Prabhu S, Flynn K, Orbach DB, Smith ER, Optimizing Cerebrovascular Surgical and Endovascular Procedures in Children via Personalized 3-Dimensional Printing, Journal of Neurosurgery, Pediatrics (in press)