Research Domains and Clusters
The Diabetes Research Center at Mayo Clinic is comprised of seven scientific cores residing in three different conceptual domains.
Mass Spectrometry, Metabolomics, and Mitochondrial Biology Core
Goal: To make available state-of-the-art methodologies to the investigators to study in vivo metabolic processes at the whole-body and tissue levels in humans and animals and ex vivo in tissue and cell lines.
- Offer three analytical services.
- Act as a resource center for investigators to design studies that involves the use of the methodologies available in the core.
- Provide consultative services to assist with data interpretation.
- Facilitate integration of the data from genomics (e.g., epigenetic), proteomics, and transcriptomics with metabolomics analysis and functional and phenotype analysis.
Provide comprehensive, reproducible, cost-effective and quality-controlled methods for measuring various parameters relevant to mitochondrial biology, stable isotope labeled tracers in plasma and tissue samples, and large-scale and targeted metabolite measurement. Services include:
- Comprehensive study of mitochondrial biology.
- Stable isotope tracers to advance understanding of in-vivo kinetics of glucose, fatty acids, and amino acids.
- Measure fatty acid deposition and release from specific regions.
- Measure protein synthesis and degradation at regional levels, synthesis rates of individual plasma and tissue proteins, and identification of de novo proteins synthesized from old and damaged proteins.
- Provide large-scale (qualitative) metabolomics in biological fluids and measurements of targeted metabolites in plasma and tissues:
- amino acid metabolites, ceramides, and lipid metabolites in tissues.
- citric acid cycle substrates in plasma and tissues.
Goal: Help researchers conduct the best possible DNA studies to understand the complex disease of diabetes and identify the best possible treatments for the disease; and why such treatments succeed or fail.
- Develop and maintain a core of genotyping facilities to enable appropriate identification of common genetic variation and its impact on metabolism or drug response.
- Utilize these facilities to support the investigation of variation in response to metabolic or pharmacologic stimuli.
- Provide technical assistance and detailed training to research fellows, staff, and faculty to promulgate and facilitate the study of the contribution of genetic variation to metabolic disease and drug response.
Serve as a resource supporting investigators who are interested in the contribution of common genetic variation to inter-individual variation in key physiologic processes. Provide appropriate technical assistance and training to investigators. Provide advice regarding appropriate methodology. Support assay design, genotyping and analysis.
Autonomic Neurovascular Core
Goals: Provide the investigative community with an array of techniques to study the autonomic nervous system and blood flow in humans. Provide a consultative and training resource. Train young investigators in the appropriate use of these techniques and continue to focus on developing new and cutting-edge approaches to address these topics.
- Provide a resource comprising well-validated tests of autonomic function, supported by a large normative database and will serve as a crucial resource for clinical trials on diabetic complications.
- Consolidate and facilitate access to several state-of-the-art techniques available across the Mayo Clinic campus that can be used to study the autonomic nervous system and peripheral blood flow and hemodynamics in humans.
- Develop and incorporate training modules and consultative services targeted at trainees, young investigators, and established investigators interested in diabetes and related conditions.
- Serve as a focal point of innovation so that new techniques can be adopted and developed.
- Leverage other institutional resources to enhance the effectiveness of the Autonomic Neurovascular Core.
The methodology includes a validated symptom questionnaire called the Autonomic Symptom Profile, scales to quantify orthostatic hypotension, several relatively noninvasive techniques to assess different elements of autonomic nervous system, and the Composite Autonomic Severity Score (CASS), which uses data from quantitative sudomotor axon reflex tests, cardiovagal protocol, beat-to-beat blood pressure (BP) responses to the Valsalva maneuver, and head-up tilt.
These techniques, either alone or as part of the CASS, can be used to characterize patients and also track the efficacy of interventions.
Tracer Methodology and Human Phenotyping Core
Goal: Provide logistical and educational support for both experienced and novice investigative teams that use isotopic tracers to study metabolic diseases. This may include consultation and review with the Core Director to ensure the desired measures can be accomplished with the proposed study design as it relates to tracer methods.
- Provide high quality, efficient preparation of isotopic tracers for metabolic studies to investigative teams.
- Provide education in the theory and practice of tracer methodology for postdoctoral fellows who desire a career in clinical investigation.
A collaborative relationship by measuring the kinetics of multiple fuels (glucose, lipid, amino acids) in a single study to maximize the amount of information obtained. Support involves:
- coordinating the use of existing space, education opportunities, and research pharmacy expertise to eliminate overlap and accelerate protocol development.
- using a centralized management model to provide precisely the amount of support appropriate to the needs of each investigative team.
- preparing research fellows for careers in clinical investigation.
- provide consultative services to investigators new to tracer methodology.
Animal Phenotyping and Procedures Core
This core is critically dependent on a collaborative program between Mayo Clinic in Arizona (MCA), Mayo Clinic in Rochester (MCR), and the Center for Metabolic and Vascular Biology at Arizona State University (CMVB at ASU) with laboratory and clinical research resources on both the campuses.
Goal: Provide a collaborative research environment for investigators to study the pathogenesis of type 2 diabetes mellitus, insulin resistance, obesity and cardiovascular disease. The basic knowledge of disease pathogenesis will generate novel hypotheses that can be tested in clinical research.
- Provide state-of-the-art metabolic phenotyping laboratories for genetically manipulated mouse models of diabetes and obesity.
- Provide state-of-the-art mass spectrometry–based proteomics facilities for DRC investigators studying animal and human models of diabetes and obesity.
- Develop and incorporate training modules and consultative services targeted at trainees, young investigators, and established investigators interested in diabetes and related conditions. Specific focus will be on the needs of the trainees and young investigators.
- Provide mechanisms of innovative integration of proteomics techniques with mouse metabolic phenotyping methodologies.
To facilitate research for investigators at both sites and obviate the need for mouse transfer and quarantine, it was deemed important to provide a uniform, coordinated site of measurement capabilities at both sites. Quality-control measures will be put in place to ensure uniformity of data. Services include:
- Provide body composition analysis.
- Provide energy expenditure testing.
- Provide glucose tolerance tests.
- Assess insulin sensitivity using glucose tracers.
Goal: To refine and improve the infrastructure of the existing clinical trials unit that would facilitate participation in early- and late-phase clinical trials and to train young investigators in the appropriate use of these resources and continue to focus on developing new and cutting-edge approaches.
- To maintain a core aimed at providing infrastructure for successful conduct of clinical trials targeted at the prevention and treatment of both type 1 and type 2- diabetes.
- To facilitate the conduct of early- and late-phase clinical trials.
- To facilitate participation from local ethnic minority populations.
- To provide education and training in the conduct of clinical trials for young investigators.
Core can improve the efficiency, productivity, effectiveness, and multidisciplinary nature of diabetes research by providing diabetes researchers access to community-based centers and academic institutions equipped and designed to be able to support rigorous research. Core will support comparative effectiveness research strategies based on innovative and rational pharmacologic/technologic interventions to prevent and treat type 1 and type 2- diabetes and improve patient-important outcomes.
Biomedical Statistics and Data Management Core
Goal: To leverage institutional biostatistical and data management support to provide efficient, collaborative, and shared resources to advance the treatment of diabetes through the use of advanced research methodology by ensuring efficient access to the core's expertise and scientific rigor for the research.
- Consultative Expertise: Maintain an "open door" to provide access to biostatisticians at all stages of research, facilitate investigator development, and promote sound research.
- Biostatistics: Provide biostatistical expertise in the areas of trial design and analysis.
- Data Management: Implement a data management plan that provides support for all project activities.
Core will ensure the highest degree of focus on the analytical and data management considerations for this program of research. The Biostatistics Core is an integral component dedicated to ensuring that key scientific input is readily available during the design phase of all research emanating from this program. The core will assume the responsibility for ensuring data integrity and timely completion of study reports so that the maximum scientific value of DRC research will be obtained.