CANDIDATE: Kaitlin A. Freeberg is a second-year graduate student in the Department of Integrative Physiology at the University of Colorado (CU) Boulder. Ms. Freeberg proposes to gain novel research training by taking advantage of opportunities provided by a recently initiated NIH R01-funded clinical trial of the nutraceutical compound, nicotinamide riboside (NR), for decreasing systolic blood pressure (SBP) and arterial stiffness in middle-aged and older adults with above-normal SBP. She seeks to perform additional experiments within this clinical trial by leveraging blood samples collected under the parent grant to determine the efficacy and mechanisms of action of NR for decreasing inflammation in this subject population. Her immediate goal is to gain the fundamental clinical and translational research experience and professional skills necessary to perform independent biomedical research. Her long-term goal is to become an academic scientist investigating creative strategies for improving cardiovascular (CV) function and health. CAREER DEVELOPMENT PLAN: Ms. Freeberg?s career development consists of: 1) gaining mentored experience conducting a randomized, placebo-controlled, double-blind, phase IIa clinical trial; 2) learning state-of-the-art biochemical and cellular techniques and molecular analyses to strengthen her translational research skills; 3) training in biostatistics and bioinformatics; 4) further developing her professional skills through formal coursework and participation in weekly laboratory journal clubs, university seminars, and national scientific conferences; and 5) interacting regularly with her mentoring team. ENVIRONMENT: Ms. Freeberg?s training plan environment is exceptional. The sponsor, Dr. Seals, has >30 years of NIH-funded research experience and a successful record of mentoring trainees in translational research to improve CV function in groups with increased CV disease (CVD) risk. Co- mentor Dr. You is a biostatistician at the CU Anschutz Medical Campus. Co-mentor Dr. Ziemba, who directs our biochemistry core research and training program, has extensive experience designing and performing innovative cellular and molecular translational research experiments. RESEARCH: Above-normal SBP and arterial stiffness increase CVD risk. Increases in SBP and arterial stiffness are mediated, in part, by chronic inflammation. NR supplementation is a promising healthspan- extending strategy to reduce inflammation, SBP and arterial stiffness in adults with above-normal SBP. This research will investigate the efficacy of NR treatment for reducing chronic inflammation (Aim 1) and identify treatment-induced changes in molecular signaling pathways via targeted plasma metabolomics analyses (Aim 2) that directly inhibit inflammatory cytokine production (Aim 3). Changes in these mechanistic processes will then be related to changes in SBP and arterial stiffness.
Increases in systolic blood pressure contribute to arterial dysfunction and increased risk of cardiovascular diseases and other chronic conditions. This project will provide insight into the mechanistic action of nicotinamide riboside, a caloric-restriction mimicking nutraceutical intervention, for reducing inflammation, a key pathway in the development of high blood pressure and arterial stiffness, in adults with above-normal blood pressure. Overall, this project has the ability to elucidate the anti-inflammatory effects of a novel, healthy- lifestyle mimicking intervention for lowering blood pressure, improving arterial health and function, and reducing the risk of cardiovascular diseases in a clinically-relevant and significant proportion of the population.
