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Quantitative Analysis of Blood Flow in Sickle Cell Disease

镰状细胞病血流的定量分析

基本信息

批准号：
8306238
负责人：
John Matthew Higgins
金额：
$ 15.92万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-20 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8306238
关键词：
Behavior Blood Blood flow Blood specimen Caliber Cell Adhesion Molecules Cell membrane Cellular biology Chemicals Clinical Clinical Pathology Complex Computer Architectures Development Plans Devices Disease Doctor of Medicine Doctor of Philosophy Engineering Environment Erythrocytes Functional disorder Health Sciences Health Technology Hematocrit procedure Hemoglobin Hydration status Image Analysis Kinetics Laboratories Mathematics Measurement Measures Medicine Mentors Microfluidic Microchips Microfluidics Microscopic Modeling Modification Monitor Osmolar Concentration Oxygen Oxygen measurement, partial pressure, arterial Pathology Patients Phenotype Physics Plasma Process Property Recording of previous events Research Project Grants Sampling Severities Severity of illness Sickle Cell Sickle Cell Anemia Sickle Hemoglobin Stratification Symptoms Systems Biology Testing Time Training Translating Translations Treatment Protocols United States National Institutes of Health Universities Variant Work career career development computer science environmental intervention experience hydroxyurea medical schools multi-scale modeling novel polymerization pressure professor programs response sickling skills small molecule

项目摘要

DESCRIPTION (provided by applicant): The candidate is a clinical fellow in pathology proposing a 5-year development plan for a career in academic clinical laboratory medicine. The candidate has training and professional experience in clinical pathology, applied mathematics, and computer science. He will be mentored and advised by both H. Franklin Bunn, M.D., Professor of Medicine at Harvard Medical School, and by Lakshminarayanan Mahadevan, Ph.D., Professor of Applied Mathematics at Harvard University and of Systems Biology at Harvard Medical School. Dr. Bunn is an expert in the field of red blood cell biology and pathophysiology. Professor Mahadevan is an expert in the field of biophysical modeling. The candidate's advisory team includes Sangeeta Bhatia, M.D., Ph.D., Associate Professor of Health Sciences and Technology at MIT, Carlo Brugnara, M.D., Professor of Pathology at Harvard Medical School, David Dorfman, M.D., Ph.D., Associate Professor of Pathology at Harvard Medical School, and William Eaton, M.D., Ph.D., Chief of Chemical Physics, NIH. This career development program will promote his further acquisition of the theoretical and practical skills necessary to model and understand disorders of blood flow and to translate those findings to the clinical laboratory or the bedside. The research project will investigate the causes of vaso-occlusion in sickle cell disease. Vaso-occlusion is a process occurring at multiple levels of scale: nanoscopic hemoglobin polymerization, microscopic cellular sickling and endothelial response, and macroscopic vessel occlusion. Control parameters for vaso-occlusion include hemoglobin S concentration, oxygen tension, hematocrit, endothelial phenotype, vessel diameter, and pressure gradient. This dynamic pathophysiologic process will be studied using microfluidic devices and computational image analysis. Preliminary work has demonstrated the ability to evoke, reverse, perturb, and inhibit the occlusion of sickle cell blood in a limited artificial microfluidic environment. The proposed work will explore the process of vaso-occlusion, its response to perturbation, and its correlation with patient symptom severity by (1) characterizing the dynamics of occlusion in an existing limited microfluidic device under a range of control parameter values, (2) expanding the range of initial conditions, parameter values, and blood specimen manipulations, and (3) enhancing the experimental device with adhesion molecules, complex geometries, and the introduction of small molecules. This work will advance our understanding of the mechanism of this disease process and has potentially immediate applications for translation to the clinical laboratory for monitoring and treatment stratification of sickle cell patients. This work may also serve as a test bench for the optimization of existing treatment regimens and the identification of altogether novel therapies.

描述（由申请人提供）：候选人是病理学临床研究员，提出5年的学术临床检验医学发展计划。候选人具有临床病理学、应用数学和计算机科学方面的训练和专业经验。他将受到哈佛医学院医学教授H. Franklin Bunn医学博士和哈佛大学应用数学教授和哈佛医学院系统生物学教授Lakshminarayanan Mahadevan博士的指导和建议。Bunn博士是红细胞生物学和病理生理学领域的专家。Mahadevan教授是生物物理建模领域的专家。