Dr. Shehadeh has a B.S. in Microbiology, a Ph.D and postdoctoral training in computational biology, and postdoctoral training in cardiovascular research. She is a junior faculty on the tenure track in the Division of Cardiology at the Department of Medicine at UM. This career development award supplements her research background with senior mentorship and lab-based and didactic training in core molecular biology, vascular aging and atherosclerosis. The research plan is based on preliminary observations which support the hypothesis that a microRNA, miR-30e, is down regulated with age and regulates major atherogenic pathways. This hypothesis will be tested along three aims: (1) to assess the effect of miR-30e on cholesterol biosynthesis and bioactivity via Hmgcr regulation, in young, middle-aged, and old atherogenic mice (2) identify the molecular mechanism of miR-30e-mediated regulation of smooth muscle markers, and (3) identify mechanism by which miR-30e suppresses osteogenic differentiation of mesenchymal stem cells (MSCs). Dr. Shehadeh will undertake a career development plan consisting of: 1. Experimental research, laboratory instruction, journal clubs and scientific review and development by her mentors and colleagues. 2. Coursework through the University of Miami graduate program. 3. Intramural seminars and national conferences and symposia. 4. Training in the responsible conduct of research. 5. Guidance by a scientific advisory committee consisting of five senior MDs and one senior Ph.D. 6. Grant writing, grant review, and development of a transition plan aimed at independence. Dr. Shehadeh's molecular and vascular biology mentorship will primarily come from Dr. Keith Webster, director of Vascular Biology Institute (VBI). Dr. Webster is an accomplished NIH-funded vascular biologist who studies mechanisms of hypoxia-regulated angiogenesis, atherosclerosis, aging of mesenchymal stem cells, and therapeutic potential of endothelial progenitor cells. Dr. Shehadeh will be co-mentored by Dr. Joshua Hare, director of the Interdisciplinary Stem Cell Institute (ISCI). Dr. Hare is NIH-funded to investigate basic and clinical research on mesenchymal and cardiac stem cells, has a long track record of research in regenerative medicine, and will provide guidance regarding key mechanistic pathways believed to underlie differentiation of mesenchymal stem cells. This mentorship team will guide Dr. Shehadeh's career development as she executes the research aims of this application in the 3 years, writes her R01 on the 2nd year, and transitions to independence as a research scientist.

Public Health Relevance

This career development award provides Dr. Shehadeh, a research faculty, with salary and research support to pursue a career development plan aimed at making her an independent research scientist studying mechanisms for interrogating atherogenic pathways with age. Dr. Shehadeh will be mentored by two senior scientists at the University of Miami and conduct research using a promising new molecule (microRNA) to reduce atherogenic burden with age and investigate mechanisms for this treatment.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
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National Institute on Aging Initial Review Group (NIA)
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Kohanski, Ronald A
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University of Miami School of Medicine
Internal Medicine/Medicine
Schools of Medicine
Coral Gables
United States
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Ding, Wen; Li, Jihe; Singh, Jayanti et al. (2015) miR-30e targets IGF2-regulated osteogenesis in bone marrow-derived mesenchymal stem cells, aortic smooth muscle cells, and ApoE-/- mice. Cardiovasc Res 106:131-42
Grabner, Alexander; Amaral, Ansel P; Schramm, Karla et al. (2015) Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy. Cell Metab 22:1020-32
Hu, Xinyang; Wu, Rongrong; Shehadeh, Lina A et al. (2014) Severe hypoxia exerts parallel and cell-specific regulation of gene expression and alternative splicing in human mesenchymal stem cells. BMC Genomics 15:303
Rodriguez-Menocal, Luis; Faridi, Mohd Hafeez; Martinez, Laisel et al. (2014) Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling. Am J Physiol Heart Circ Physiol 306:H641-53
Shehadeh, Lina A; Hare, Joshua M (2013) Ribonucleic acid biomarkers for heart failure is there a correlation between heart and blood transcriptomics? JACC Heart Fail 1:477-9
Omran, Ahmed; Elimam, Dalia; Webster, Keith A et al. (2013) MicroRNAs: a new piece in the paediatric cardiovascular disease puzzle. Cardiol Young 23:642-55