T32 Translational Addiction Research Fellowship Program

T32 转化成瘾研究奖学金计划

• 批准号: 10628649
• 负责人: Julie A Blendy
• 金额: $ 32.91万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10628649
• 关键词: Fellowship Program; Research; addiction

Addictions and the associated public health problems of HIV transmission, crime and violence, exact a severe toll on our nation, costing billions annually in health care, lost productivity, and incarceration. These inter-related problems have only worsened during the global COVID-19 pandemic, still ongoing. We need to speed the "forward" translation of recent neuroscience and neurogenetic knowledge into more effective clinical treatments for the addictions. Conversely, for addiction treatments with some known efficacy, we can now apply new neuroscience and genetic tools in "backward-translation" -- e.g., finding why a treatment works well for some individuals, yet not at all for others. To help meet the need for skilled translational researchers, this application proposes continuation of a successful (32 total trainees; 16 in the current funding period) NIDA T32 Translational Addiction Research Fellowship at the University of Pennsylvania. The training program (4 pre- and 4 post- doctoral positions) makes explicit a long-standing translational tradition at Penn, integrating clinical and basic research strengths to create trainees, whether clinical or preclinical, Ph.D.s or M.D.s, who will accelerate addiction science in the next decade. The emphasis on translation is reflected at each level of the program - through the Co-PIs (clinical and basic, Drs. Childress and Blendy), the internal and external advisors, the formal didactics, the "dual" (clinical - preclinical) journal clubs, and in the trainees' mentored research projects. The translational emphasis of the program is driven by the recognition that addictions are complex disorders, multi- determined by interaction of genetic vulnerabilities, exposure to drug, and a host of modulating (e.g., early trauma, stress, cultural norms) influences. Trainees are thus offered state-of-the-art knowledge about these interacting determinants through a didactic series specific to the program, and through mentored projects that may range from molecular and genetic studies, to brain systems (neuroscience and neuroimaging, including PET), to clinical treatment trials, and drug policy. This wide range of choices is enabled by the long history of excellence in addiction research at the University, reflected in several interacting academic research entities (Penn Center for Studies on Addiction; Translational Research Laboratories/CNB; Center for AIDS Research; Penn PET Center; the Complex Systems Lab) offering skilled, successful mentors to the Fellowship. Mentored research also takes place within several affiliated treatment settings (VA, Presby-Penn, local opioid treatment clinics, and mobile HIV Prevention units), critical for translating new research findings into the "real world”.

吸毒成瘾以及艾滋病毒传播、犯罪和暴力等相关的公共卫生问题， 我们的国家每年在医疗保健、生产力损失和监禁方面花费数十亿美元。这些相互关联的 在全球COVID-19大流行期间，问题只会恶化，目前仍在持续。我们需要加快 将最新的神经科学和神经遗传学知识“向前”转化为更有效的临床治疗方法 为了成瘾。相反，对于一些已知疗效的成瘾治疗，我们现在可以应用新的 “向后翻译”中的神经科学和遗传工具--例如，为什么治疗对某些人有效 对个人而言，对其他人而言，根本不是。为了帮助满足熟练的翻译研究人员的需求，该应用程序 建议继续一个成功的（32名学员; 16在目前的资助期）NIDA T32翻译 宾夕法尼亚大学成瘾研究奖学金。培训计划（4个术前和4个术后） 博士职位）明确了宾夕法尼亚大学长期以来的翻译传统，将临床和基础 研究优势，培养受训人员，无论是临床或临床前，博士或医学博士，谁将加速 未来十年的成瘾科学对翻译的重视体现在该计划的每个级别- 通过共同PI（临床和基础，奇尔德里斯和Blendy博士），内部和外部顾问，正式 教学法，“双”（临床-临床前）杂志俱乐部，并在学员的指导研究项目。的 该计划的翻译重点是由认识到成瘾是复杂的疾病，多， 由遗传脆弱性、暴露于药物和一系列调节（例如，早期 创伤、压力、文化规范）的影响。因此，学员可以获得有关这些方面的最新知识。 通过特定于该计划的教学系列，以及通过指导项目， 可能范围从分子和遗传研究，脑系统（神经科学和神经成像，包括 PET），临床治疗试验和药物政策。这种广泛的选择是由悠久的历史， 卓越的成瘾研究在大学，反映在几个相互作用的学术研究实体 (Penn成瘾研究中心;转化研究实验室/CNB;艾滋病研究中心; 宾州PET中心;复杂系统实验室）提供熟练的，成功的导师奖学金。指导了 研究也在几个附属的治疗环境中进行（VA，Presby-Penn，当地阿片类药物治疗 诊所和移动的艾滋病毒预防单位），这对于将新的研究成果转化为“真实的世界”至关重要。

项目成果

Linking the CHRNA5 SNP to drug abuse liability: From circuitry to cellular mechanisms.

• DOI: 10.1016/j.neuropharm.2021.108480
• 发表时间: 2021-03-15
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Brynildsen JK;Blendy JA
• 通讯作者: Blendy JA

Chromatin-mediated alternative splicing regulates cocaine-reward behavior.

• DOI: 10.1016/j.neuron.2021.08.008
• 发表时间: 2021-09-15
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Xu SJ;Lombroso SI;Fischer DK;Carpenter MD;Marchione DM;Hamilton PJ;Lim CJ;Neve RL;Garcia BA;Wimmer ME;Pierce RC;Heller EA
• 通讯作者: Heller EA

Glucagon-Like Peptide-1 Receptor Activation in the Ventral Tegmental Area Decreases the Reinforcing Efficacy of Cocaine.

腹侧被盖区胰高血糖素样肽 1 受体激活会降低可卡因的增强功效。

• DOI: 10.1038/npp.2015.362
• 发表时间: 2016
• 期刊: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
• 作者: Schmidt,HeathD;Mietlicki-Baase,ElizabethG;Ige,KelseyY;Maurer,JohnJ;Reiner,DavidJ;Zimmer,DerekJ;VanNest,DuncanS;Guercio,LeonardoA;Wimmer,MathieuE;Olivos,DianaR;DeJonghe,BartC;Hayes,MatthewR
• 通讯作者: Hayes,MatthewR

Effects of LY466195, a selective kainate receptor antagonist, on ethanol preference and drinking in rats.

LY466195（一种选择性红藻氨酸受体拮抗剂）对大鼠乙醇偏好和饮酒的影响。

• DOI: 10.1016/j.neulet.2016.12.050
• 发表时间: 2017
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: VanNest,Duncan;Hernandez,NicoleS;Kranzler,HenryR;Pierce,RChristopher;Schmidt,HeathD
• 通讯作者: Schmidt,HeathD

Altering Nitrogen Heterocycles of AZD2461 Affords High Affinity Poly(ADP-ribose) Polymerase-1 Inhibitors with Decreased P-Glycoprotein Interactions.

改变 AZD2461 的氮杂环可提供高亲和力的聚 (ADP-核糖) 聚合酶 1 抑制剂，并减少 P-糖蛋白相互作用。

• DOI: 10.1021/acsomega.8b00896
• 发表时间: 2018
• 期刊: ACS omega
• 影响因子: 4.1
• 作者: Reilly,SeanW;Puentes,LauraN;Hsieh,Chia-Ju;Makvandi,Mehran;Mach,RobertH
• 通讯作者: Mach,RobertH