Molecular Risk Assessment in Hereditary Melanoma

遗传性黑色素瘤的分子风险评估

• 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
• 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

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。该K24的发展目标旨在培训和指导以患者为导向的医生科学家进行创新研究，将分子遗传学转化为分子医学。申请人是一名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的遗传学方面的贡献而得到广泛认可。他在马萨诸塞州总医院（MGH）建立并指导了一个充满活力的黑色素瘤遗传学项目，在哈佛建立了一个丰富的遗传性黑色素瘤登记处，其中有来自世界各地的250多个黑色素瘤家族，并领导了韦尔曼光医学中心的皮肤癌遗传学实验室和MGH黑色素瘤和色素性病变中心-一个致力于黑色素瘤患者护理的临床单位;这种多学科的基础设施提供了独特的机会，把基本的发现带到床边。申请人指导了许多医学生，专业和亚专业学员和博士后研究员正确进行以患者为导向的分子研究。指导计划包括一套核心培训目标：（1）培养学术成功所需的技能，包括执行合理科学基础的能力，以连贯性和说服力撰写赠款和手稿，并提供简洁和令人信服的演示文稿，（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，最后到项目的科学方法;（4）在科学共同体的背景下成熟。这些目标将通过执行四大科学目标来实现：（1）建立一个稳健的模型（称为MelaPRO）来估计CDKN 2A/CDK 4突变携带者概率，（2）在缺乏CDKN 2A/CDK 4改变的高风险家族中鉴定RB途径基因的编码变体，（3）开发灵活，准确，高通量平台来评估CDKN 2A/CDK 4/MC 1 R基因型和（4）设计用于黑皮质素-1-受体（MC 1 R）基因中的患者衍生变体的新功能测定。通过拟议的K24中期职业发展奖，申请人将能够为黑色素瘤患者开发几种有形产品，扩大他自己对变异组学重要新兴领域的知识，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。