Immune Activation and Immunosenescence Biomarkers and Cardiovascular Disease Risk - ¿
DESCRIPTION (provided by applicant): Dr. Nels C. Olson, PhD is a postdoctoral fellow in the Laboratory for Clinical Biochemistry Research (LCBR) in the Department of Pathology and Laboratory Medicine at the University of Vermont College of Medicine. He is currently supported by an NHLBI-funded T32 training award and is mentored by Dr. Russell P. Tracy, PhD, director of the LCBR, Professor of Pathology and Biochemistry, and the Department's Vice-Chair for Research. Dr. Olson earned a PhD in cell and molecular biology at the University of Vermont under the mentorship of Dr. Albert van der Vliet, PhD as an NIEHS-funded T32 predoctoral trainee. Dr. Olson's research thesis utilized isolated primary airway epithelial cell culture systems, hypoxia-inducible factor-1a (HIF-1a) gene silencing, and nitric oxide synthase 2 genetic knock out mice, to elucidate the roles of nitric oxide and HIF-1 signaling in airway epithelial barrier regulation during allergic airway disease. Dr. Olson's career goals are to become an independent faculty member with a research program that involves the joint application of epidemiological, biochemical, genetic, and biostatistical methods to develop inflammation-, immunity-, and coagulation-based biomarker assays for implementation and use in cardiovascular disease (CVD) epidemiological and clinical research studies. His goals are to elucidate disease etiology, translate molecular findings to human populations, improve CVD risk stratification, and guide individual treatment strategies. In order to achieve these goals, Dr. Olson chose to pursue postdoctoral training in molecular epidemiology with Dr. Tracy following the completion of his basic science oriented PhD. Dr. Olson's current research involves investigating biomarkers of inflammation (TNF-a, C-reactive protein), immunity (Th1 and Th2 cells, CD4+ memory and naive cells), and coagulation (thrombin, coagulation factors XII, XI and IX) as CVD risk factors in large population-based epidemiological cohort studies (e.g., the Multi-Ethnic Study of Atherosclerosis (MESA); the Cardiovascular Health Study (CHS)). During his postdoctoral fellowship, Dr. Olson, has published 8 manuscripts and was awarded the American Heart Association's (AHA) Roger R. Williams award for genetic epidemiology and the prevention and treatment of atherosclerosis. Dr. Olson serves on the ancillary studies committee for the NHLBI-MESA study, and attends and presents at the MESA steering committee meetings, and the AHA Epidemiology Scientific Sessions. He also serves on the Early Career Advisory Committee of the Cardiovascular Research Institute of Vermont. Dr. Olson's research application proposes to measure 17 T- and B-lymphocyte and monocyte populations, and novel plasma-based biomarkers of immunocyte activation, at the baseline examinations of MESA and CHS. Using a case-cohort study design with 2,400 participants free of CVD at baseline, Dr. Olson will evaluate the prospective relationships of these immune cell subpopulations with the future onset of myocardial infarction (MI) and the composite endpoint of incident MI and new onset angina. The research hypothesis contains three main features: 1) high levels of pro-inflammatory cells (Th1, Th17, B2, CD8+, and classical monocytes (CD14+CD16-)) with direct roles in atherosclerosis will increase the risk of CVD events; 2) a high degree of chronic adaptive immune activation will increase the risk of CVD events; and, 3) high levels of anti-inflammatory cells (Th2, Treg, B1, non-classical monocytes, T follicular helper cells) will decrease the risk of CVD events. The proposed research reflects Dr. Olson's career goals in the joint application of multiple disciplines: epidemiological cohort studies, immunobiology assay development, and biostatistical analyses. During the K99 phase of the award, Dr. Olson will gain expertise in research assay development and laboratory management (e.g., budget preparation, technician supervision, etc.) by supervising a laboratory budget (beyond that awarded by the K99) and a laboratory technician while developing assays proposed in the research. Dr. Tracy will provide these resources, oversee the research progress, and provide mentoring. Dr. Olson will obtain academic training in biostatistics and epidemiology, required for his goals of becoming an independent investigator in epidemiological research, by completing an on-line Master's in Public Health degree offered by the University of Vermont over the first 2 years of the K99/R00 award. He will also receive individual mentoring on specific aspects of the research project from a multi-disciplinary Advisory Committee. During the R00 phase of the award Dr. Olson will execute an independent research program developing biomarkers related to B cell biology, B cell immunoglobulin subclasses, and immune cell co- stimulation and metabolism, and evaluating their relationships with incident CVD; areas which are not being pursued by Dr. Tracy. To continue to build an independent research program, Dr. Olson will develop and prepare an R01 in the first year of the R00 phase and submit the application during the second R00 year. Dr. Tracy is the Director of the Core Laboratory for CHS and MESA and has over 500 peer-reviewed manuscripts in CVD-epidemiology, inflammation, immunity, biomarker assays, and several other research areas. Dr. Tracy currently has 16 actively funded contracts and awards and is centrally involved in several national and international epidemiology studies, clinical studies, and clinical trials. Dr. Tracy is committed to mentoring and training Dr. Olson to transition into a successful independent faculty position.
