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National Research Science Award - Medical Scientist

项目来源

美国卫生和人类服务部基金(HHS)

项目主持人

MAAS, STEFAN

项目受资助机构

WASHINGTON UNIVERSITY

立项年度

2019

立项时间

未公开

项目编号

3T32GM007200-45S1

项目级别

国家级

研究期限

未知 / 未知

受资助金额

105322.00美元

学科

未公开

学科代码

未公开

基金类别

TRAINING, INSTITUTIONAL

关键词

未公开

参与者

YOKOYAMA, WAYNE M.

参与机构

NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

项目标书摘要：? DESCRIPTION (provided by applicant): This is a renewal application to support the Medical Scientist Training Program (MSTP) at Washington University in St. Louis. The overarching goal of the MSTP is to provide in-depth pre-doctoral training in clinical medicine and biomedical research for individuals desiring careers as physician-scientists. The applicant pool is strong and in the past funding period, the MSTP made significant strides in recruiting diversity students. Medical training is provided by the School of Medicine and research training is carried out in the interdisciplinary graduate programs of the Division of Biology and Biomedical Sciences, and in the Departments of Biomedical Engineering and Anthropology. Together, these graduate programs encompass nearly all contemporary areas of biomedical research. The basic components of the MSTP are: 1) Two years of the preclinical medical school curriculum; 2) Coursework in a biomedically relevant discipline; 3) Three or more years of original, hypothesis-driven research leading to completion of a doctoral thesis; 4) At least 15 months of clinical training; and 5) A wealth of academic and social programs designed to enhance the program and cohesiveness of the student body. The M.D. and Ph.D. degrees are awarded jointly at the successful completion of both components which typically takes 7-8 years, a period shortened by integrating both curricula. Upon completion of subsequent postgraduate training, MSTP alumni will be prepared to enter the workforce as physician-scientists. Based on the track record of this program, the vast majority will join the faculty of te nation's medical schools while others will contribute to the nation's biomedical research enterprise in government laboratories, biotechnology firms, and the pharmaceutical industry. Regardless of their position, their MSTP training will allow them to bridge the gap between the basic laboratory and the clinic. The success of this program is due to strong institutional support and continued funding of this grant. Thus, this renewal application seeks continued support for 55 students annually for 36 months each with the goal of graduating 20-25 MSTP students each year over the period of this grant.

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  • 1.Altered hemodynamics contribute to local but not remote functional connectivity disruption due to glioma growth

    • 关键词：
    • Functional connectivity; glioma; hemodynamic lags; mouse model;neurovascular uncoupling;DEFAULT MODE NETWORK; CEREBRAL-BLOOD-FLOW; LOW-GRADE GLIOMA;BRAIN-TUMOR; SPONTANEOUS FLUCTUATIONS; MOUSE-BRAIN; FMRI; STROKE;CORTEX; ANESTHESIA
    • Orukari, Inema E.;Siegel, Joshua S.;Warrington, Nicole M.;Baxter, Grant A.;Bauer, Adam Q.;Shimony, Joshua S.;Rubin, Joshua B.;Culver, Joseph P.
    • 《Journal-of-Cerebral-Blood-Flow-and-Metabolism Symposium atInternational Symposium on Cerebral Blood Flow, Metabolism and Function》
    • 2020年
    • JUL 07, 2019
    • Yokohama, JAPAN
    • 会议

    Glioma growth can cause pervasive changes in the functional connectivity (FC) of brain networks, which has been associated with re-organization of brain functions and development of functional deficits in patients. Mechanisms underlying functional re-organization in brain networks are not understood and efforts to utilize functional imaging for surgical planning, or as a biomarker of functional outcomes are confounded by the heterogeneity in available human data. Here we apply multiple imaging modalities in a well-controlled murine model of glioma with extensive validation using human data to explore mechanisms of FC disruption due to glioma growth. We find gliomas cause both local and distal changes in FC. FC changes in networks proximal to the tumor occur secondary to hemodynamic alterations but surprisingly, remote FC changes are independent of hemodynamic mechanisms. Our data strongly implicate hemodynamic alterations as the main driver of local changes in measurements of FC in patients with glioma.

    ...

  • 2.Role of Sirtuins in Retinal Function Under Basal Conditions

    • 关键词：
    • Sirtuins; NAD(+); Retinal degeneration; Neurodegeneration;Photoreceptors; Retina;HISTONE DEACETYLASE; PROTEIN; SIRT6; MICE; DEGENERATION; METABOLISM;NAD(+); GENE
    • Lin, Jonathan B.;Kubota, Shunsuke;Mostoslavsky, Raul;Apte, Rajendra S.
    • 《17th International Symposium on Retinal Degeneration 》
    • 2018年
    • SEP 19-24, 2016
    • Kyoto, JAPAN
    • 会议

    Sirtuins are NAD(+)-dependent enzymes that govern cellular homeostasis by regulating the acylation status of their diverse target proteins. We recently demonstrated that both rod and cone photoreceptors rely on NAMPT-mediated NAD(+) biosynthesis to meet their energetic requirements. Moreover, we found that this NAD(+)-dependent retinal homeostasis relies, in part, on maintenance of optimal activity of the mitochondrial sirtuins and of SIRT3 in particular. Nonetheless, it is unknown whether other sirtuin family members also play important roles in retinal homeostasis. Our results suggest that SIRT1, SIRT2, SIRT4, and SIRT6 are dispensable for retinal survival at baseline, as individual deletion of each of these sirtuins does not cause retinal degeneration by fundus biomicroscopy or retinal dysfunction by ERG. These findings have significant implications and inform future studies investigating the mechanisms underlying the central role of NAD(+) biosynthesis in retinal survival and function.

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