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PROJECTS AND CORES
The three projects investigate the mechanisms of the p66Shc deficiency in mice from different angles: |
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Project 1: Bioenergetics, metabolism and lifespan in p66-/- mice
(PI, Jon Jay Ramsey, Veterinary Medicine: Department of Molecular Biosciences, UC Davis).
The aims of Project 1 are focused on determining the influence of Shc proteins on metabolic response to high-fat/high-carbohydrate diets, the role Shc-based modifications play in the metabolic response to caloric restriction, and whether or not a diet (low-carbohydrate) that induces chronic increases in capacity for P-oxidation, ketone body metabolism and gluconeogenesis can mirror the effects of caloric restriction and decreased Shc levels. |
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Project 2: Microarray and mitofunction of Shcs
(PI, Gino Cortopassi, Veterinary Medicine: Department of Molecular Biosciences, UC Davis).
The goals of Project 2 are to: a) identify the mechanism(s) by which Shc KO mice resist adiposity and stress; b) understand the mechanism by which Shc depletion extends median lifespan on caloric restriction; and c) identify Shc-inhibitory drugs that could be used to improve insulin signaling and healthy aging across species. |
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Project 3: The effect of p66Shc and diet on stem cell regeneration and stress resistance
(PIs, PierGiuseppe Pelicci, Department of Experimental Oncology, IEO and
Rosario Rizzuto, Department of Biomedical Science, UNIPD).
The overall goal of Project 3 is to understand how p66Shc knockout and diet controls the regenerative and differentiation potentials of stem cells, and the consequences of this regulation in determination of resistance to cell stress and adiposity. |
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The projects are supported by three cores: |
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- Core A: Administrative Core
(Director, Gino Cortopassi, Ph.D., Veterinary Medicine: Department of Molecular Biosciences, UC Davis).
Core A provides administrative services to the four
Projects and two other Cores of this Program Project. The administrative core is central to the synergistic
interaction of the Projects and Cores.
- Core B: Mouse Management and Pathology Core
(Director, Kent Lloyd, Ph.D., Center for Comparative Medicine, UC Davis).
Core B provides pathogen-free and genetically
standardized p66Shc(-/-) mice for the project, and to assess the age-related clinical and anatomic pathology of
p66Shc(-/-) mice. In addition, the core will carry out a lifespan study, on the lifespan of p66Shc, caloric
restriction (CR), p66Shc+CR, and control animals in a barrier facility.
- Core C: Biostatistics, Bioinformatics and Data Management Core
(Director, Kyoungmi Kim, Ph.D., Division of Biostatistics, Department of Public Health Sciences, UC Davis).
Core C provides biostatistics and
bioinformatics services to support all program project investigators. Core C also provides comprehensive data
management and data sharing services for all the projects in collaboration with the Administrative Core.
Figure. Organizational Structure for the Program Project
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