GENOMICS & BIOINFORMATICS

Computer rendering of DNA strand
Many of the faculty members in the Department of Pharmacology utilize the human genome sequence and molecular structure to define how and where pharmacological processes occur. Knowledge of the human genome allows our faculty to define the target of pharmacologically important molecules. Defining the molecular structure of the target protein allows pharmacological mechanisms of molecules to be defined. The centers and facilities that aid in this research include the Mass Spectrometry Center, the Nuclear Magnetic Resonance Center, the X-ray Crystallography Center, and the DNA Array Facility and the Center for Computational Pharmacology (featured below).

DNA/Gene Array Facility

The Department of Pharmacology in collaboration with the University of Colorado Cancer Center has established a DNA Array Facility for the analysis of gene expression profiles in different experimental paradigms. The goal of our facility is to allow analysis of gene expression profiles in a high throughput fashion. This allows large numbers of genes to be analyzed simultaneously.

The facility analyzes expression arrays hybridized with nucleic acids from human tissue, as well as a variety of animal models, including mouse, rat and yeast. The goal of the facility is to have 40000 human genes, 20000 mouse genes and 10000 rat genes formatted for high throughput screening in the year 2000. The entire yeast genome is formatted for screening. Both cDNA and oligonucleotide arrays are being developed. Investigators in virtually all disciplines including cancer biology, development, immunology, alcohol addiction, neurobiology, and others are using the facility. Current Research The DNA Array Facility works closely with the Computational Pharmacology Center for analysis of the DNA gene expression changes that are measured in different experimental settings. Bioinformatics is essential for understanding the relevance of gene expression changes in human disease. Thus, an integrated state-of-the-art DNA Array Facility is closely aligned with the bioinformatics faculty in the department.

Center for Computational Pharmacology

The Center for Computational Pharmacology is investigating the application of advanced computational techniques to the analysis of high throughput molecular assays. The main focus of the Center is the analysis of gene expression array data. Expression arrays quantitate mRNA abundance of tens of thousands of genes simultaneously.

The massive quantity of data presents both challenges and opportunities in analysis. The Center has developed methods for inferring network models from expression data, as well as identifying clusters of co-expressed genes, inducing expression-based discriminators for diagnosis and other outcomes, and probabilistic models of the underlying gene expression distributions. Additionally, the Center is also active in the development of database search and interchange techniques for array data, and has developed systems for managing the biomedical literature relevant to the activities and interactions of thousands of genes.

Churchill, Mair E. A.
Professor
PhD, 1987, Johns Hopkins Univ. 
Structure and mechanism in gene regulation; biophysical and structural studies of protein-nucleic acid and protein-protein complexes in chromatin and bacterial pathogenesis.

Costello, James
Assistant Professor
PhD, 2009, Indiana Univ.
Systems and network biology approaches to disentangle signaling pathways in cancer development; Computational modeling of how therapeutic compounds function across different genomic backgrounds.

Cramer, Scott D.
Professor
PhD, 1992, Univ. of California, Santa Cruz
The molecular dissection of signaling pathways in prostatic cells, the identification of prostate progenitor or stem cells, and understanding epithelial-stromal interactions in normal and abnormal ductal morphogenesis.

Ford, Heide, L.
Professor
PhD, 1995, Univ. of Rochester
My laboratory studies the parallels between normal development and tumorigenesis/metastasis with a focus on the role of the Six1/Eya transcriptional complex in TGF-beta signaling, epithelial to mesenchymal transition, cancer stem cells, and metastasis.

Hunter, Lawrence E.
Professor
PhD, 1989, Yale Univ.
Computational biology, bioinformatics, gene expression array analysis, natural language processing, biomedical ontologies, machine learning.

Port, J. David
Professor
PhD, 1989, Univ. of Utah
G-protein linked receptors and their regulation; regulation of mRNA stability.