Molecular Risk Assessment in Hereditary Melanoma

遗传性黑色素瘤的分子风险评估

基本信息

批准号：
8669945
负责人：
HENSIN TSAO
金额：
$ 20.18万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8669945
关键词：
Accounting Affect Algorithms Alleles Area Biological Biological Assay CDK4 gene CDKN2A gene Caring Clinical Code Communities Counseling Cutaneous Melanoma Cyclic AMP Development Early Diagnosis Elements Engineering Exhibits Faculty Family Fingerprint Funding General Hospitals Generations Genes Genetic Genetic Models Genetic Programming Genetic Transcription Genomics Genotype Goals Grant Hereditary Melanoma Human Genome Project Individual Inherited K-Series Research Career Programs Knowledge Laboratories Laboratory Research Lead Lesion Liquid substance Logistic Regressions Malignant Neoplasms Manuscripts Massachusetts Mediating Medical Students Medicine Melanocortin 1 Receptor Melanocyte stimulating hormone Mentors Mentorship Methods Mission Modeling Molecular Molecular Genetics Molecular Medicine Molecular Target Mutation Pathway interactions Patient Care Patients Pattern Performance Phenotype Physicians Pigments Population Postdoctoral Fellow Predisposition Probability Process Receptor Gene Registries Research Research Infrastructure Research Personnel Retinoblastoma Risk Risk Assessment Science Scientist Signal Transduction Skin Skin Cancer System Techniques Testing Time Training Translating Variant Writing alpha-Melanocyte stimulating hormone base cancer genetics career design flexibility genetic pedigree high risk innovation medical specialties melanoma molecular marker multidisciplinary mutation carrier next generation novel patient oriented programs research study response risk variant screening skills sound success theories

项目摘要

DESCRIPTION (provided by applicant): Rapid gains in genetics and genomics pose both great opportunities and challenges for the contemporary physician. The developmental goals of this K24 are intended to train and mentor patient-oriented physician scientists to conduct innovative research that will transform molecular genetics into molecular medicine. The applicant is a mid-career clinician-scientist whose investigational program focuses on applications of genomic science to the management of hereditary melanoma patients. The candidate is widely recognized for his contributions in the genetics of melanoma predisposition and progression. He founded and directs a vibrant Melanoma Genetics Program at the Massachusetts General Hospital (MGH), established a rich Hereditary Melanoma Registry at Harvard with over 250 melanoma families from throughout the world and leads both the Skin Cancer Genetics Laboratory in the Wellman Center for Photomedicine and the MGH Melanoma and Pigmented Lesion Center- a clinical unit dedicated to the care of melanoma patients; this multidisciplinary infrastructure provides unique opportunities to bring basic discoveries to the bedside. The applicant has mentored many medical students, specialty and subspecialty trainees and postdoctoral fellows in the proper conduct of patient-oriented molecular research. The mentorship plan includes a set of core training objectives: (1) to develop facility in skills required for academic success including the ability to execute the fundamentals of sound science, to write grants and manuscripts with coherence and cogency and to deliver a concise and convincing presentation, (2) to critically evaluate science for design and interpretation, (3) to effectively frame the scientific method from techniques to experiments to projects and finally to programs and (4) to mature within the context of a scientific community. These will be achieved through the execution of 4 broad scientific Aims: (1) create a robust model (termed MelaPRO) to estimate CDKN2A/CDK4 mutation carrier probability, (2) identify coding variants in RB-pathway genes in high-risk families lacking CDKN2A/CDK4 alterations (3) develop a flexible, accurate, high-throughput platform to assess CDKN2A/CDK4/MC1R genotypes and (4) devise novel functional assays for patient-derived variants in the melanocortin-1-receptor (MC1R) gene. Through the proposed K24 mid-career development award, the applicant will be able to develop several tangible products for the melanoma patient, to expand his own knowledge of important emerging area of variomics and, most importantly, to find the necessary time to mentor trainees and junior faculty and sustain a productive research laboratory.

描述（由申请人提供）：遗传学和基因组学的快速发展为当代医生带来了巨大的机遇和挑战。 K24 的发展目标旨在培训和指导以患者为中心的医师科学家进行创新研究，将分子遗传学转化为分子医学。申请人是一位职业生涯中期的临床医生科学家，其研究项目侧重于基因组科学在遗传性黑色素瘤患者管理中的应用。该候选人因其在黑色素瘤易感性和进展遗传学方面的贡献而受到广泛认可。他在马萨诸塞州总医院 (MGH) 创立并指导了一个充满活力的黑色素瘤遗传学项目，在哈佛大学建立了一个包含来自世界各地 250 多个黑色素瘤家族的丰富的遗传性黑色素瘤登记处，并领导了威尔曼光医学中心的皮肤癌遗传学实验室和MGH 黑色素瘤和色素病变中心 - 一个致力于黑色素瘤患者护理的临床单位；这种多学科基础设施提供了将基本发现带到临床的独特机会。申请人指导了许多医学生、专业和亚专业实习生以及博士后研究员正确进行以患者为导向的分子研究。导师计划包括一系列核心培训目标：（1）培养学术成功所需的技能，包括执行可靠科学基础知识的能力，连贯和有说服力地撰写资助和手稿，以及提供简洁和令人信服的论文的能力。演示，(2) 批判性地评估科学的设计和解释，(3) 有效地构建从技术到实验到项目，最后到计划的科学方法，(4) 在科学界的背景下成熟。这些将通过执行 4 个广泛的科学目标来实现：(1) 创建一个稳健的模型（称为 MelaPRO）来估计 CDKN2A/CDK4 突变携带者概率，(2) 识别缺乏的高风险家庭中 RB 通路基因的编码变异CDKN2A/CDK4 改变 (3) 开发一个灵活、准确、高通量的平台来评估 CDKN2A/CDK4/MC1R 基因型，以及 (4) 设计新颖的黑皮质素 1 受体 (MC1R) 基因中源自患者的变异的功能测定。通过拟议的 K24 职业中期发展奖，申请人将能够为黑色素瘤患者开发几种有形产品，扩展自己对重要的变异组学新兴领域的知识，最重要的是，找到必要的时间来指导学员和初级教师并维持一个富有成效的研究实验室。