Successes

NIH Director's Pioneer Award

Professor Gary Pielak of the UNC Chemistry Department was chosen for the 2006 NIH Director's Pioneer Award.

Now in its third year, the Pioneer Award is a key component of the NIH Roadmap for Medical Research. The program supports exceptionally creative scientists who take highly innovative approaches to major challenges in biomedical research.

Ryszard Kole Awarded Roadmap Grant

Professor Ryszard Kole of the UNC Department of Pharmacology was awarded a Roadmap grant entitled Modulation of Alternative Splicing by HTS Identified Compounds.

Eleven Roadmap Grants Awarded to UNC Investigators in 2006

• Integrated Biomedical Research Training Program (R90) (Bill Marzluff, PI)
• Integrated Biomedical Research Training Program (T90) (Bill Marzluff, PI)
• Chemical Probes for Uncovering Differential Regulators of Apoptosis in Cells
  (Mohanish Deshmukh, PI)
• Screening for RhoC Activation and its modulation by GEFs (Louis Hodgson, PI)
• Inhibitor Screens for Five MAPK Kinase Kinases Important in Human Disease
  (Gary Johnson, PI)
• Developing HTS Assays for Novel Intracellular Regulators of Integrin Activation
  (Tina Leisner, PI)
• Screen for molecules inhibiting histone pre-mRNA processing (Bill Marzluff, PI)
• NIH Director’s Pioneer Awards Program: Gary Pielak
• CTSA Planning Grant (Eugene Orringer, PI)
• Robust Computational Framework for Predictive ADMETox Modeling (Alexander Tropsha, PI)
• Human Enterohepatic Cell Model for Predictive Toxicology (Jeffrey MacDonald, PI)

Eight Roadmap grants awarded to UNC investigators in 2005

We’re Number One! AGAIN! A new round of Roadmap grants was awarded in September 2005. UNC-Chapel Hill was awarded 8 of these (descriptions below), more than any other institution.

• Major Challenges in Clinical Medicine: An Overview for Basic Scientists (Rudy Juliano, PI) to conduct short courses aimed at exposing basic science graduate students and postdocs to issues in translational medicine.
• UNC Multidisciplinary Clinical Research Career Development Program (Eugene Orringer, PI) for a Multidisciplinary Clinical Research Career Development Program  designed to train clinical research scholars. The objectives are to recruit a cohort of fellows and junior faculty members drawn from at least four disciplines and then prepare them for careers in multidisciplinary clinical research.
• Real-Time Fluorescence Assays of RGS Domain GAP Activity (David Siderovski, PI) to identify small molecule tools for further advancing knowledge of RGS protein function in specific GPCR signaling pathways, and also to facilitate identification of lead compounds for developing RGS protein directed therapeutics, we will modify and validate novel, real-time, fluorescence-based assays of RGS protein function for automated high throughput molecular screening: a fluorescence resonance energy transfer (FRET)-based binding assay that employs cyan fluorescent protein-labeled G-alpha subunits and yellow fluorescent protein-labeled RGS proteins, a single-turnover GTP hydrolysis assay using a fluorescent sensor for inorganic phosphate production, and an assay of G-alpha nucleotide binding and hydrolysis that employs the fluor-modified nucleotide BODIPY(r) FL 2'-(or-3')-O-(N-(2-aminoethyl)urethane)guanosine 5'-triphosphate.
• A High Throughput Screen for Telomerase Assembly (Michael Jarstfer, PI) to develop a high throughput screen that reports on the interaction between the catalytic subunit of human telomerase (hTERT) and one domain of its RNA subunit (the CR4-CR5 domain). We will use the screen to refine the understanding of the hTERT-hTR interaction and to identify molecules that perturb the assemblage of telomerase. In essence, these molecules will generate, in situ, a dominant negative telomerase complex. These could be lead compounds for anticancer drug discovery.
• MEKK2/3-MEK5 Protein Interaction/Activation/ERK5 Pathway (Bruce Cuevas, PI) to develop an assay for ERK5 pathway signaling based on this PB1 domain interaction that will facilitate high throughput screening of potential ERK5 signaling inhibitors that function through disrupting PB1 domain association. Targeting MEKK2/3- MEK5 interaction by small molecule inhibitors will markedly disrupt ERK5 activation and selectively inhibit stimulus-specific activation of cytokine expression in multiple cell types, and thus provide new opportunities for therapeutic intervention in diseases involving inflammation.
• Chemical Diversity Libraries From Medicinal Plants (Kuo-Hsiung Lee, PI) to generate pilot-scale chemical diversity libraries, which will be used for high-throughput screening (HTS) by the Molecular Libraries Screening Center Network (MLSCN). The compounds included in these libraries will be derived from medicinal plants - both isolated natural products and synthetic modified derivatives. Naturally occurring compounds representing unique chemical diversity classes will be isolated, purified, and characterized using modern chemical, physical, and spectral techniques.
• Carolina Exploratory Center for Cheminformatics Research (Alexander Tropsha, PI) to promote multidisciplinary, multi-institutional collaboration among researchers in computational chemistry, chemical biology, datamining, computer science, and statistics to address critical issues in Cheminformatics in the context of Molecular Libraries Initiative at NIH. The research subjects include developing procedures to calculate molecular descriptors, biologically relevant diversity and similarity metrics, data analytical tools and specialized methodologies for chemical library design and virtual screening, and rigorously validated biological and ADMETox property predictors.
• UNC Interdisciplinary Obesity Training (IDOT) (Barry Popkin, PI) to support postdoctoral fellows.
• Roadmap-like: Carolina Center of Nanotechnology Excellence (Rudy Juliano, PI) to bring together recent pioneering breakthroughs at UNC in nanotechnology with the world class excellence in the understanding/treatment of cancer in the Lineberger Cancer Center for the delivery of therapeutic, detection and imaging agents for the diagnosis and treatment of cancer.

Roadmap Grants Awarded to UNC Investigators in 2004

• Dr. Balfour Sartor and colleagues submitted a P20 proposal, Non-Invasive Approaches to Assessing Inflammation, which was funded by the NIH in September 2004
• Vice-Chancellor Dan Reed, Dr. Terry Magnuson, and colleagues submitted a P20 called The Carolina Center for Exploratory Genetics, which was funded by the NIH in September 2004.
• Dr. Barry Popkin and colleagues submitted a P20, An Interdisciplinary Strategy for Obesity, which was funded by the NIH in September 2004.
• Dr. Ronald Rindfuss and colleagues of the Carolina Population Center submitted a Roadmap proposal, Population, Land Use and Health in Frontier Regions, which was funded by the NIH in September 2004.
• Dr. Gary Johnson received a P20 award to plan for a nanomedicine center.
• Dr. Harry Guess of the Department of Epidemiology was awarded a Roadmap grant, a U01 that is part of a national network , PROMIS, of 6 primary research sites and 1 statistical coordinating center. Dr. Darren DeWalt is now the Principal Investigator.