Daniel Tyrrell, Ph.D.Daniel Tyrrell, Ph.D., Assistant Professor, Molecular and Cellular Pathology, was recently awarded an R00 to study the increased risk of vascular disease in older adults. Tyrrell, who joined the department in August, had an active K99 grant funded at the University of Michigan by the National Institutes of Health, to study, “Cerebrovascular Mitochondrial Function in Aging and Ischemic Injury.”
This grant mechanism is designed to support rising faculty members, and is Tyrrell's first. The proposed research will examine mechanisms of why older adults are at increased risk of vascular disease.
"Current treatments for dementia are inadequate for people of all ages," Tyrrell says. “My proposed research will determine how mitochondria and inflammation in blood vessels in the brain enhance cognitive decline with the goal of improving treatment for dementia and related diseases in blood vessels of the brain.”
Vascular pathology in the brain is present in up to 80% of people with Alzheimer’s disease (AD) and vascular dementia is the second leading cause of dementia behind AD. Tyrrell will work with Steve Austad, Ph.D., Chair, UAB Department of Biology, Erik Roberson, M.D., Ph.D., Professor, Neurology, and Scott Ballinger, Ph.D., Professor, Jianhua Zhang, Ph.D., Professor, and Rakesh Patel, Ph.D., Vice Chair, UAB Pathology, along with Louise McCullough, M.D., Ph.D., University of Texas at Houston.
Tyrrell has discovered that cerebral blood vessels in aged mice have evidence of mitochondrial dysfunction leading to increased STING and IL-6 inflammation and blood-brain barrier breakdown. The mechanisms of vascular contributions to cognitive impairment and dementias (VCID) in aging remain unclear. Therefore, the objective of this study is to determine how cerebrovascular mitochondrial dysfunction impacts cognitive function in aging.
One target of the study is to determine how age-related cerebrovascular mitophagy and mitochondrial dysfunction impacts the blood-brain barrier (BBB) and cognitive function during natural aging and in a model of vascular dementia induced by cerebral hypoperfusion.
A second aim is to examine how cerebrovascular inflammation impacts the BBB and cognitive function in a model of vascular dementia with aging. Tyrrell plans to employ novel mitophagy reporter mice and mice with enhanced mitochondrial function, in addition to using cell-type specific conditional knockout mouse models and pharmacologic approaches. He will study blood-brain barrier integrity and cognitive function in aging to distinguish himself from his mentors and allow him to develop a cutting-edge independent career in examining VCID.