Pancreatic Beta-Cell Regeneration: Expanding the functional Mass

胰腺β细胞再生：扩大功能质量

• 批准号: 8514587
• 负责人: Justin Pierce Annes
• 金额: $ 15.37万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-16 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514587
• 关键词: Address; Alleles; Animals; Apoptosis; B-Lymphocytes; Candidate Disease Gene; Caring; Cell Count; Cell Culture System; Cell Culture Techniques; Cell Line; Cell physiology; Cells; Cellular biology; Clinic; Clinical; Country; Data; Development; Diabetes Mellitus; Disease; Disease Progression; Doctor of Philosophy; Endocrine; Environment; Event; Failure; Fostering; Functional disorder; Future; Genes; Genetic; Glucokinase; Glucose; Goals; Growth; Health; Healthcare; Human; Human Genetics; Hyperinsulinism; Hyperplasia; In Vitro; Individual; Inherited; Insulin; Interleukin-2; Internal Medicine; Islet Cell; Joints; Knowledge; Laboratories; Light; Mentorship; Metabolic; Modeling; Molecular; Molecular Profiling; Mus; Natural regeneration; Newborn Infant; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Pancreas; Pathology; Patient Care; Patients; Penetrance; Physiological; Preventive; Principal Investigator; Regenerative Medicine; Reporter; Research; Research Personnel; Risk; Scientist; Stem cells; Structure of beta Cell of islet; Therapeutic; Time; Transgenic Mice; Vision; Work; base; blood glucose regulation; care burden; career; cell growth; diabetic; diabetic patient; direct patient care; genome wide association study; global health; in vivo; insight; insulin secretion; interest; meetings; pregnant; prevent; programs; promoter; regenerative; research study; response; restoration; skills; small molecule; success; therapeutic target

DESCRIPTION (provided by applicant): In July of 2008, I will graduate as the first joint internal medicine and clinical genetics trainee in the country. This unique opportunity informs my vision of how I can integrate clinical and scientific work in a way that will advance patient care. I believe most disease has a hereditary basis, either as a result of highly penetrant alleles (autosomal dominant conditions) or weakly penetrant alleles (low-risk association alleles). In either case, the causative alleles are a window into the mechanisms underlying the pathophysiology and represent potential therapeutic targets. As a scientist, with a specific interest in diabetes, I will use this understanding to direct my research. As a clinician, I will staff a weekly endocrine genetics clinic. Over time, the clinic will increasingly be focused on low penetrance risk alleles which will be used to guide patient-specific preventive and therapeutic care. In the long-term, I hope to advance the treatment of diabetes through laboratory-based bench research and through insights garnered from direct patient care. This proposal describes a 5-year research program to acquire expertise in the fields of ( cell biology, islet ( cell physiology, and regenerative medicine. At present, the molecular mechanisms that are responsible for (-cell failure and (-cell regeneration remain obscure. This research plan is focused on characterizing the molecular mechanisms of (-cell replication, on identifying small-molecules that promote (-cell growth and on elucidating the basic physiology of (-cells. With a better understanding of the underlying mechanisms of (-cell regeneration, we will acquire insight into the basic pathophysiology of diabetes. Furthermore, this research program provides a platform for me to launch a career as an independent investigator. The studies proposed here will be carried out under the mentorship of Douglas Melton Ph.D., an accomplished investigator in the field of regenerative medicine with specific expertise in Diabetes. I will have regular meetings with collaborators and advisors to review my progress and to promote my career advancement I will also participate in scientific courses to broaden my knowledge and skills. Finally, the success of this proposal and of my career will be fostered by the extraordinary research environment created by the consortium of the Stem Cell and Regenerative Medicine Department and the BWH Genetics Division. PUBLIC HEALTH RELEVANCE: Diabetes and its related complications are a major global health care burden. At present, oral therapy is typically of limited value and intensive insulin therapy, even when performed by the most attentive patients, fails to avert most disease related pathology. This proposal is focused on harnessing the regenerative capacity of islet (-cells to prevent the onset and progression of disease.

描述（由申请人提供）： 2008年7月，我将毕业于该国的第一位联合内科和临床遗传学员。这个独特的机会使我对如何以一种可以改善患者护理的方式整合临床和科学工作的愿景。我认为大多数疾病都是由于高度渗透等位基因（常染色体显性疾病）或弱渗透剂等位基因（低风险关联等位基因）而具有遗传基础。无论哪种情况，因果等位基因都是通往病理生理学基础机制并代表潜在治疗靶标的机制的窗口。作为一名科学家，对糖尿病具有特别的兴趣，我将使用这种理解来指导我的研究。作为临床医生，我将为每周内分泌遗传学诊所工作。随着时间的流逝，该诊所将越来越集中于低渗透风险等位基因，这些等位基因将用于指导患者特定的预防和治疗护理。从长远来看，我希望通过基于实验室的基础研究以及通过直接患者护理获得的见解来促进糖尿病的治疗。 该提案描述了一项为期5年的研究计划，该计划获得了（细胞生物学，胰岛（细胞生理学和再生医学）领域的专业知识。目前，负责的分子机制（ - 细胞衰竭和（ - 细胞的再生仍然晦涩难懂）。该研究计划集中在促进（-clecell of Simply of Smill of（-cc）的（ - con）（ - con）的（-cccel of Smill-cc）（上）（上）（上）（上）（上）（ - concel of Simple of（-cc），（ - c。 （ - 细胞的基本生理学，更好地理解（ - 细胞再生的基本机制）（我们将了解糖尿病的基本病理生理学。此外，该研究计划为我提供了一个平台，为我提供了一个独立研究员的职业。 此处提出的研究将在Douglas Melton Ph.D.的指导下进行，该研究人员是再生医学领域的研究人员，具有糖尿病方面的特定专业知识。我将与合作者和顾问定期开会，以审查我的进步并促进我的职业发展，我还将参加科学课程以扩大我的知识和技能。最后，该提案和我职业生涯的成功将由干细胞和再生医学部和BWH遗传学部门创建的非凡研究环境促进。 公共卫生相关性：糖尿病及其相关并发症是全球主要的医疗保健负担。目前，口服治疗通常具有有限的价值和强化胰岛素治疗，即使是由最细心的患者进行的，也无法避免与疾病相关的大多数病理学。该提议的重点是利用胰岛的再生能力（ - 防止疾病的发作和进展。

项目成果

Adult tissue sources for new β cells.

新β细胞的成人组织来源。

• DOI: 10.1016/j.trsl.2013.11.012
• 发表时间: 2014
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Nichols,RobertJ;New,Connie;Annes,JustinP
• 通讯作者: Annes,JustinP

Erdheim-Chester disease presenting with cutaneous involvement: a case report and literature review.

伴有皮肤受累的埃尔德海姆-切斯特病：病例报告和文献综述。

• DOI: 10.1111/j.1600-0560.2010.01650.x
• 发表时间: 2011
• 期刊: Journal of cutaneous pathology
• 影响因子: 1.7
• 作者: Volpicelli,ElgidaRadoncipi;Doyle,Leona;Annes,JustinP;Murray,MichaelF;Jacobsen,Eric;Murphy,GeorgeF;Saavedra,ArturoP
• 通讯作者: Saavedra,ArturoP

Risks of Presymptomatic Direct-to-Consumer Genetic Testing.

• DOI: 10.1056/nejmp1006029
• 发表时间: 2010-09-16
• 期刊: NEW ENGLAND JOURNAL OF MEDICINE
• 影响因子: 158.5
• 作者: Annes, Justin P.;Giovanni, Monica A.;Murray, Michael F.
• 通讯作者: Murray, Michael F.