Candidate: Daniel Trott, Ph.D. is an Assistant Professor at the University of Texas at Arlington. Dr. Trott's research is focused on the interaction between inflammation and age-related arterial dysfunction. Dr. Trott's long-term goal is to independently direct an extramurally funded laboratory with research focused on the interaction of the aging immune system and vasculature in both pre-clinical models and in humans. Career Development: This award will support Dr. Trott's career development by building on his existing training in aging and vascular biology. Specifically, Dr. Trott will receive extensive training in the planning and execution of studies assessing vascular and immune outcomes in older adults. The career development plan outlines a coordinated effort to train the candidate in areas including: vascular biology of aging, assessment of vascular function in humans, human endothelial cell and immune cell phenotyping, and, attendance at regular aging and vascular seminar series as well as other meetings within the university and nationally. Environment: The University of Texas at Arlington is an ideal environment for Dr. Trott's career development. This environment provides all of the resources needed to complete the proposed studies. Further, his mentoring team allows for collaboration with experts in aging, vascular biology, and immunology. The University of Texas at Arlington also provides a rich environment for formal and informal training in career development. Research: The central hypothesis of this research project is that T cells mediate age-related arterial dysfunction. First, we hypothesize that T cells infiltrate the perivascular tissue around large elastic and resistance arteries and mediate age-related arterial dysfunction. To test this, we will assess arterial function, immune cell infiltration and inflammatory subtypes in young and old mice with T cells intact or depleted. In addition, we will employ adoptive transfer to determine whether aged T cells preferentially home to the vasculature and induce dysfunction. Second, we hypothesize that T cells directly mediate age-related arterial dysfunction in older adults. To test this hypothesis we will adoptively transfer T cells from young, middle aged and older healthy human donors to NOD-scid/?cnull/A2 humanized mice and assess immune cell infiltration, inflammation and arterial function. We will also assess arterial function, plasma free radicals and endothelial and T cell phenotype in the human donors to determine the relationship between these parameters and the degree of dysfunction induced in the recipient mice. The results from these studies will provide insight into the etiology of age-related arterial dysfunction and identify previously unexplored targets for diagnostics and intervention with the significant goal of maintaining cardiovascular health in the elderly.

Public Health Relevance

Cardiovascular disease (CVD) is the leading cause of death in the United States and aging is a primary risk factor for CVD primarily due to dysfunction of the arteries. Arterial inflammation appears to play a role in this dysfunction but the precise link is not clear. The results from this proposal will indicate whether T cells from the immune system directly mediate age-related vascular dysfunction and have potential to identify specific targets that may be used for early detection and/or drug treatment of CVD and reduce CVD burden in the elderly.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AG061271-02
Application #
9914190
Study Section
Neuroscience of Aging Review Committee (NIA)
Program Officer
Fuldner, Rebecca A
Project Start
2019-04-15
Project End
2024-03-31
Budget Start
2020-05-01
Budget End
2021-03-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Texas Arlington
Department
Other Health Professions
Type
Schools of Nursing
DUNS #
064234610
City
Arlington
State
TX
Country
United States
Zip Code
76019