Dr. Reilly has a track record in unique mechanistic patient oriented research (POR) and mentorship at the University of Pennsylvania (Penn). His Cardiometabolic Research Program is dedicated to human translational and genomic studies of atherosclerotic cardiovascular disease (ASCVD) and its risk factors. His program is based in Penn's Cardiovascular and Translational Institutes and highly integrated into the training missions sponsored by Penn's Clinical and Translational Science Award. This provides an outstanding environment for translational POR and for mentoring K24 trainees. He has had a track record of continuous NIH funding, mentorship of multiple physician scientists in translational POR, and numerous high-impact translational publications led by over a dozen trainees, several of whom have established their own independent POR careers. Dr Reilly recognizes the challenges to incorporating basic science and cutting edge translational technologies into academic careers in POR. He is committed to training young clinical investigators in these approaches and mentoring them to independent careers in POR. In this application, he proposes to (1) augment his scientific and mentoring skills and devote more time to mechanistic POR, (2) provide increased time and structure in mentoring new clinical investigators in the conduct of mechanistic POR, and (3) pursue new innovative POR in order to provide a unique training environment and POR framework for mentoring young clinical investigators. Although recent genomic discoveries have identified novel associations with ASCVD and its risk factors, the key challenge remains in demonstrating how these loci cause disease and can be advanced for clinical application and therapeutic targeting. The proposed K24 research will recruit healthy humans to generate induced pluripotent stem (iPS) cells from adipose tissue biopsies. The iPS cells will be used to address pilot studies tissue-specific functional studies of recent genomic discoveries for heart disease, (a) SORT1, a novel LDL-cholesterol and myocardial infarction locus, in regulation of hepatocyte lipoproteins and, (b) ABO, a locus for risk endothelial risk biomarkers and myocardial infarction, in regulation of endothelial secreted proteins. Dr Reilly will dedicate 40% effort to this K24 proposal (5% to augment his mentorship and POR skills;10% to the research proposal;and 25% to mentoring new investigators) through reduction in administrative and clinical duties. The K24 award provides the ideal mechanism to expand his mechanistic POR program while simultaneously dedicating significant effort to train young clinical investigators.

Public Health Relevance

Project Narrative Dr. Reilly has a track record in unique mechanistic patient oriented research (POR) and mentorship at the University of Pennsylvania. His Cardiometabolic Research Program is dedicated to translational and genomic studies of human atherosclerosis and its risk factors. In this application, he proposes to (1) augment his scientific and mentoring skills and devote more time to mechanistic POR, (2) provide increased time and structure in mentoring new clinical investigators in the conduct of mechanistic POR, and (3) pursue new innovative POR in order to generate a unique training environment and POR framework for mentoring young clinical investigators.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL107643-02
Application #
8263968
Study Section
Special Emphasis Panel (ZHL1-CSR-X (F1))
Program Officer
Carlson, Drew E
Project Start
2011-05-13
Project End
2016-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
2
Fiscal Year
2012
Total Cost
$165,806
Indirect Cost
$12,282
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Ballantyne, Rachel L; Zhang, Xuan; Nuñez, Sara et al. (2016) Genome-wide interrogation reveals hundreds of long intergenic noncoding RNAs that associate with cardiometabolic traits. Hum Mol Genet 25:3125-3141
Lin, Jennie; Hu, Yu; Nunez, Sara et al. (2016) Transcriptome-Wide Analysis Reveals Modulation of Human Macrophage Inflammatory Phenotype Through Alternative Splicing. Arterioscler Thromb Vasc Biol 36:1434-47
Qian, Jing; Nunez, Sara; Reed, Eric et al. (2016) A Simple Test of Class-Level Genetic Association Can Reveal Novel Cardiometabolic Trait Loci. PLoS One 11:e0148218
Golbus, Jessica R; Stitziel, Nathan O; Zhao, Wei et al. (2016) Common and Rare Genetic Variation in CCR2, CCR5, or CX3CR1 and Risk of Atherosclerotic Coronary Heart Disease and Glucometabolic Traits. Circ Cardiovasc Genet 9:250-8
Manichaikul, Ani; Wang, Xin-Qun; Zhao, Wei et al. (2016) Genetic association of long-chain acyl-CoA synthetase 1 variants with fasting glucose, diabetes, and subclinical atherosclerosis. J Lipid Res 57:433-42
Ferguson, Jane F; Xue, Chenyi; Hu, Yu et al. (2016) Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans. J Nutr Biochem 30:126-32
Shah, Rachana; Matthews, Gregory J; Shah, Rhia Y et al. (2015) Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 66:266-73
Patel, Parth N; Shah, Rhia Y; Ferguson, Jane F et al. (2015) Human experimental endotoxemia in modeling the pathophysiology, genomics, and therapeutics of innate immunity in complex cardiometabolic diseases. Arterioscler Thromb Vasc Biol 35:525-34
Lin, Jennie; Zhang, Xuan; Xue, Chenyi et al. (2015) The long noncoding RNA landscape in hypoxic and inflammatory renal epithelial injury. Am J Physiol Renal Physiol 309:F901-13
Zhong, Ming; Zhang, Hanrui; Reilly, John P et al. (2015) ABO Blood Group as a Model for Platelet Glycan Modification in Arterial Thrombosis. Arterioscler Thromb Vasc Biol 35:1570-8

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