Dr. Natalia Rost is a Stroke Neurologist at the Massachusetts General Hospital (MGH), whose goal is to become an indepentdent investigator with expertise in genetics, neuroimaging, and epidemiology to define genetic contribution to stroke and other cerebrovascular disease. Dr. Rost's career development plan brings together an outstanding team of investigators and the resources of three leading institutions including the MGH, the Framingham Heart Study (FHS), and the Broad Institute of MIT and Harvard. Dr. Rost has already obtained preliminary results of a genome-wide association study of MRI- detectable white matter hyperintensity (WMH) volume in patients with acute ischemic stroke. Under mentorship of Drs. Rosand, Wolf, deBakker, and Sorensen, Dr. Rost proposed: (1) to identify common genetic variants associated with WMH in a hospital-based cohort of patients with ischemic stroke and to replicate her findings in the Ischemic Stroke Genetics Study (ISGS) cohort of the patients with whole genome and MRI data available for analysis;(2) to determine whether genetic variants associated with WMH in AIM 1 are associated with risk of symptomatic stroke in the MGH and FHS prospective cohorts of ischemic stroke cases and their matched controls, and (3) to translate her research findings into an applied personalized risk assessment method by developing a modified clinical-genetic risk prediction model for ischemic stroke. The overall goal of this proposal is to elucidate the role of common variation in risk and severity of WMH in patients with ischemic stroke by bringing together cutting-edge methods for neuroimaging and genetic analysis and a team with expertise in cerebrovascular disease, neuroimaging, and complex disease genetics. This well-defined mentored patient-oriented research proposal, in concert with a structured didactic curriculum of advanced statistical, epidemiologic, and genetic coursework, will provide Dr. Rost with the skills and mentorship that are essential for her to develop an independent career in cerebrovascular research at the cutting edge of genomic science. Public Health Relevance: Despite modern advances in prevention and treatment, stroke remains the leading cause of adult disability and second leading cause of death worldwide. Dr. Rost's proposed career development plan has an outstanding potential to advance our knowledge of genetic determinants of stroke, a crucial next step toward discovery of novel risk factors and development of effective strategies for prevention and treatment of stroke.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Mentored Patient-Oriented Research Career Development Award (K23)
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NST-2 Subcommittee (NST)
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Gwinn, Katrina
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Massachusetts General Hospital
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LaBuzetta, Jamie Nicole; Yoo, Albert J; Ali, Syed et al. (2014) Determinants of early outcomes in patients with acute ischemic stroke and proximal artery occlusion. J Stroke Cerebrovasc Dis 23:2527-32
Ruff, Ilana M; Ali, Syed F; Goldstein, Joshua N et al. (2014) Improving door-to-needle times: a single center validation of the target stroke hypothesis. Stroke 45:504-8
Corbin, Zachary A; Rost, Natalia S; Lorenzano, Svetlana et al. (2014) White matter hyperintensity volume correlates with matrix metalloproteinase-2 in acute ischemic stroke. J Stroke Cerebrovasc Dis 23:1300-6
Dalca, Adrian Vasile; Sridharan, Ramesh; Cloonan, Lisa et al. (2014) Segmentation of cerebrovascular pathologies in stroke patients with spatial and shape priors. Med Image Comput Comput Assist Interv 17:773-80
Chutinet, Aurauma; Rost, Natalia S (2014) White matter disease as a biomarker for long-term cerebrovascular disease and dementia. Curr Treat Options Cardiovasc Med 16:292
Rost, Natalia S; Sadaghiani, Saloomeh; Biffi, Alessandro et al. (2014) Setting a gold standard for quantification of leukoaraiosis burden in patients with ischemic stroke: the Atherosclerosis Risk in Communities Study. J Neurosci Methods 221:196-201
Dalca, Adrian Vasile; Sridharan, Ramesh; Cloonan, Lisa et al. (2014) Segmentation of cerebrovascular pathologies in stroke patients with spatial and shape priors. Med Image Comput Comput Assist Interv 17:773-80
Rost, Natalia S; Smith, Eric E; Nogueira, Raul G et al. (2013) Implementation of a patient selection protocol for intra-arterial therapy increases treatment rates in patients with acute ischemic stroke. J Neurointerv Surg 5 Suppl 1:i44-7
Adib-Samii, Poneh; Rost, Natalia; Traylor, Matthew et al. (2013) 17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status. Stroke 44:1609-15
Anderson, Christopher D; Biffi, Alessandro; Nalls, Michael A et al. (2013) Common variants within oxidative phosphorylation genes influence risk of ischemic stroke and intracerebral hemorrhage. Stroke 44:612-9

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