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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS064052-03
Application #
8137714
Study Section
NST-2 Subcommittee (NST)
Program Officer
Gwinn, Katrina
Project Start
2009-09-01
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
3
Fiscal Year
2011
Total Cost
$177,930
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Etherton, Mark R; Wu, Ona; Cougo, Pedro et al. (2017) Structural Integrity of Normal Appearing White Matter and Sex-Specific Outcomes After Acute Ischemic Stroke. Stroke 48:3387-3389
Giese, Anne-Katrin; Schirmer, Markus D; Donahue, Kathleen L et al. (2017) Design and rationale for examining neuroimaging genetics in ischemic stroke: The MRI-GENIE study. Neurol Genet 3:e180
(2017) 19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016, Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The CHARGE consortium. Neurol Genet 3:S2-S11
Karadeli, Hasan H; Giurgiutiu, Dan-Victor; Cloonan, Lisa et al. (2016) FLAIR Vascular Hyperintensity is a Surrogate of Collateral Flow and Leukoaraiosis in Patients With Acute Stroke Due to Proximal Artery Occlusion. J Neuroimaging 26:219-23
Gesierich, Benno; Opherk, Christian; Rosand, Jonathan et al. (2016) APOE ?2 is associated with white matter hyperintensity volume in CADASIL. J Cereb Blood Flow Metab 36:199-203
Zhang, Cathy R; Cloonan, Lisa; Fitzpatrick, Kaitlin M et al. (2015) Determinants of white matter hyperintensity burden differ at the extremes of ages of ischemic stroke onset. J Stroke Cerebrovasc Dis 24:649-54
Cloonan, Lisa; Fitzpatrick, Kaitlin M; Kanakis, Allison S et al. (2015) Metabolic determinants of white matter hyperintensity burden in patients with ischemic stroke. Atherosclerosis 240:149-53
Majersik, Jennifer J; Cole, John W; Golledge, Jonathan et al. (2015) Recommendations from the international stroke genetics consortium, part 1: standardized phenotypic data collection. Stroke 46:279-84
Wu, Ona; Cloonan, Lisa; Mocking, Steven J T et al. (2015) Role of Acute Lesion Topography in Initial Ischemic Stroke Severity and Long-Term Functional Outcomes. Stroke 46:2438-44
Giurgiutiu, Dan-Victor; Yoo, Albert J; Fitzpatrick, Kaitlin et al. (2015) Severity of leukoaraiosis, leptomeningeal collaterals, and clinical outcomes after intra-arterial therapy in patients with acute ischemic stroke. J Neurointerv Surg 7:326-30

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