TRAINING IN PHARMACOLOGY, TOXICOLOGY & PHARMACEUTICAL SCIENCES 2008 ASPET SUMMER UNDERGRADUATE RESEARCH FELLOWSHIP OPPORTUNITY at the UNIVERSITY OF CINCINNATI
The Department of Pharmacology & Cell Biophysics, College of Medicine is pleased to offer this research project as part of the 2008 summer ASPET SURF Training Program offered  by the Department  of Pharmacology & Cell Biophysics.  Students interested in this project are advised to contact Professor Jones to discover more about the project, learn what your responsibilities will be during the ten-week research training program.
2008 ASPET Project #:  08 - 002 Faculty Supervisor/Mentor: W. Keith Jones, Ph.D. Associate Professor Pharmacology & Cell Biophysics College of Medicine, University of Cincinnati Email:  joneswk@uc.edu
Project Title: Molecular Approaches to Cardiovascular Therapies using a                        “Regulomics” Strategy
Research Program Description: The Jones’ laboratory is addressing significant cardiovascular diseases and molecular interventions designed as therapeutic measures.  Cardiovascular disease remains the number one cause of death in developed countries despite decades of research into the environmental and molecular causation. In patients and experimental animal models, altered signal transduction and gene expression is associated with development of myocardial injury. In specific instances, experimental perturbation of signaling molecules elicits or ameliorates pathophysiology. Yet, animal and clinical studies with pharmacologic agents that inhibit these signals have yielded disappointing results to date. It has recently become apparent that signaling and gene expression cascades are organized as complex scale-free networks. This, and the development of genomic technologies has spawned the science of regulomics; the study of these networks. From the regulomic viewpoint, therapeutics ought not to be directed at blocking or activating single receptors, but rather at modulating expression or activation of specific sets of signaling proteins or genes. The idea is that regulating the homeostatic operation of the overall cell signaling network is critical to maintaining normal function. In order to “knock-down” the expression of specific genes and sets of genes, we are employing transcription factor decoys and short-interfering RNA (siRNA). However, the delivery of these nucleic acid molecules to tissues in vivo remains problematic. In collaboration with Dr. Theresa Reineke (Chemistry Department, University of Cincinnati), we have developed novel non-viral polymers to deliver decoys and siRNA to cells. The goal is to experimentally perturb gene expression in cardiomyocytes and to functionally dissect the transcriptional networks that underlie post-ischemic cardiac pathophysiology.
ASPET SURF Project Description: The ASPET SURF student will employ genomic and molecular techniques to analyze expression of genes in the heart after myocardial infarction (MI) or in cardiomyopathy. Based upon this and work ongoing in the lab, specific genes and sets of genes will be targeted for in vivo modulation. The student will prepare decoy/siRNA/polymer complexes and implement experiments to deliver these to isolated cardiomyocytes. Studies in intact mice will be pursued to determine efficacy, pharmacokinetics and pharmacodynamics of the DNA/polymer agents in vivo. Based upon results, studies will be initiated to perturb the transcriptional network and determine the effect upon cardiac disease models. Experimental design and scientific method will be emphasized. The student will be challenged and guided to read the scientific literature, will interact with scientists at various levels (graduate students, postdoctoral fellows, junior faculty and faculty) and participate in journal clubs. The student will be guided in scientific writing and will have the opportunity to earn authorship when the studies are published.