Positions

Overview

  • My laboratory is interested in understanding how the blood-brain barrier changes during aging. Breakdown of the blood-brain-barrier impairs leads to a poor neurovascular microenvironment and ultimately impairs cognitive function and can contribute to neurodegeneration. We aim to uncover mechanisms of vascular aging that may contribute to blood-brain barrier breakdown. Much of our previous findings have been related to alteration in mitochondrial function and inflammation within cerebrovascular vessels.

    We are also interested in exploring how CD8 T cells may take advantage of the leakier blood-brain-barrier with aging to infiltrate the brain and contribute to neurodegeneration. T cell populations change dramatically during aging with a significant reduction in naive T cell output due to age-associated thymic involution. Some populations of effector and memory T cells also increase with aging. Many of these populations also demonstrate greater levels of exhaustion and senescence with aging. Taken together, the age-associated changes in CD8 T cells appear to contribute to a variety of diseases. We are interested in exploring their role in neurodegenerative diseases.

    We primarily use murine models along with genetic and surgical manipulations. The major experiments we perform in the laboratory are immunohistochemistry, histology, flow cytometry, immunoblot, and single-cell RNA sequencing approaches.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2022 Black In Cardio: promoting diversity and representation in the cardiovascular fieldNature Reviews Cardiology.  19:717-718. 2022
    2022 Clinical, genetic, and experimental increase in soluble urokinase plasminogen activator receptor levels promotes atherosclerosis.Journal of Clinical Investigation2022
    2022 Aging Alters the Aortic Proteome in Health and Thoracic Aortic AneurysmArteriosclerosis, Thrombosis and Vascular Biology.  42:1060-1076. 2022
    2021 Ageing and atherosclerosis: vascular intrinsic and extrinsic factors and potential role of IL-6Nature Reviews Cardiology.  18:58-68. 2021
    2020 Aging impairs mitochondrial function and mitophagy and elevates interleukin 6 within the cerebral vasculatureJournal of the American Heart Association.  9. 2020
    2020 Age-Associated Mitochondrial Dysfunction Accelerates AtherogenesisCirculation Research.  298-314. 2020
    2019 Macrophage migration inhibitory factor enhances influenza-associated mortality in mice.JCI insight.  4. 2019
    2017 Pathophysiology of heart failure and frailty: a common inflammatory origin?Aging Cell.  16:444-450. 2017
    2017 Blood-based bioenergetic profiling reflects differences in brain bioenergetics and metabolismOxidative Medicine and Cellular Longevity.  2017. 2017
    2016 Blood cell respirometry is associated with skeletal and cardiac muscle bioenergetics: Implications for a minimally invasive biomarker of mitochondrial healthRedox Biology.  10:65-77. 2016
    2015 Respirometric Profiling of Muscle Mitochondria and Blood Cells Are Associated With Differences in Gait Speed Among Community-Dwelling Older AdultsJournal of Gerontology Series A: Biological Sciences and Medical Sciences.  70:1394-1399. 2015
    2015 Blood-cell bioenergetics are associated with physical function and inflammation in overweight/obese older adultsExperimental Gerontology.  70:84-91. 2015
    2015 Preparation and respirometric assessment of mitochondria isolated from skeletal muscle tissue obtained by percutaneous needle biopsyJournal of Visualized Experiments2015
    2015 Relationships between mitochondrial content and bioenergetics with obesity, body composition and fat distribution in healthy older adultsBMC Obesity.  2. 2015

    Research Overview

  • Effector Memory CD8 T cell contributions to age-related diseases
    Vascular aging contributions in a model of VCID (vascular contributions to cognitive impairment and dementia)
    Age-related changes to CD8 T cell metabolism and phenotype
  • Education And Training

  • University of Michigan–Ann Arbor Internal Medicine - Cardiology, Postdoctoral Fellowship
  • Doctor of Science in Physiology, Pathology, and Related Sciences, Wake Forest University 2017
  • Bachelor of Science or Mathematics in Kinesiology and Exercise Science, University of Michigan System : Ann Arbor 2011
  • Full Name

  • Daniel Tyrrell