Cell behavior is regulated by a complex network of intracellular and extracellular signal transduction pathways. A major focus in biomedical research over the past ten or fifteen years has been the identification and characterization of the components that make up such signaling pathways and we are now beginning to understand how such pathways are controlled, communicate with each other and, most importantly, go awry in disease states. In many ways cancer is a disease of mis-regulated signal transduction: cancer cells grow when they should not and do not die (i.e. undergo apoptosis) when they should. The underlying reason for such aberrant behavior is that cancer cells possess mutated versions of oncogenes and tumor suppressor genes. Such mutant molecules are often components of the signaling pathways that regulate cell growth, survival, motility etc. As we learn more about the normal and abnormal function of these molecules we can identify targets for new cancer therapeutics; indeed, some of the most promising new treatments for cancer are drugs that are targeted against specific signal transduction molecules.

Several laboratories at  Huntsman Cancer Institute focus on understanding specific signal transduction pathways in normal and cancerous cells providing a diverse, intellectually stimulating environment for graduate study in this competitive, fast-moving field. Signal transduction journal clubs, seminar courses and didactic lectures provide formalized instruction and an opportunity for scientific interactions between students and other investigators. The wide variety of core facilities that are available to investigators at Huntsman Cancer Institute allows graduate students in our program to tackle the most important and difficult problems using state-of-the-art techniques.

Participating Faculty

Mary Beckerle - Cells receive signals from their environment that regulate such diverse processes as cell motility, cell proliferation, and apoptosis. We are interested in understanding how cells process and integrate these signals, and how such exquisite control becomes disturbed in tumor cells. We use genetic (mouse and fly), biochemical, and cell biological approaches to dissect the signaling pathways that control cell behavior.

Donald K. Blumenthal - My laboratory is interested the structure and regulation of protein kinases, especially protein kinases involved in cancer. Protein kinases are key targets for anti-cancer drug development because of their critical roles in many aspects of neoplasia and metastasis. My laboratory employs an integrative approach to studying protein kinases that includes using synthetic peptides and biophysical techniques for structural studies, as well as biochemical and fluorescence techniques to characterize protein kinase activities in vitro and in living cells.

Frank Fitzpatrick - Students and post-doctoral fellows investigate the role of inflammation and inflammatory mediators as a risk factor and as host-defense responses against cancer. Scientists working in this laboratory must have a strong commitment to quantitative methodology and a desire to characterize biological processes according to laws of chemistry. Investigations focus on pharmacological mechanisms of modulating tumor suppressor and oncogenic processes, and techniques include chemical and instrumental analysis; cytometric analysis; gene expression analysis.

David Jones - Our lab studies the relationships between the control of gene expression and tumor cell responsiveness to chemotherapeutics. Our work aims to define new molecular targets for the development of novel cancer therapies. To accomplish our goals we rely on genomic technologies combined with molecular and cell biology techniques.

Erik M. Jorgensen - Our lab is interested in the proteins which regulate neurotransmission. We have demonstrated that the steps in the synaptic vesicle cycling depend on the phosphorylation state of lipids. We are using the nematode C. elegans to identify mutants which are defective in these processes.

Betty Leibold - We are interested in the pathways by which mammalian cells respond to and adapt to stresses, including metals, oxygen and nitrogen radicals and hypoxia. We are determining the stress-activated signal transduction pathways and genes whose expression is required for survival during stress. We use mammalian cell culture, transgenic mouse models, biochemistry and genetics using C. elegans to determine how organisms survive during stress.

Andres Villu Maricq - Nervous system development and plasticity. Study of genes required for neuronal differentiation, pathfinding, and synaptic organization. Genetic and molecular analysis of neuronal function in Caenorhabditis elegans and generation of transgenic models.

Baldomero M. Olivera - Our lab is interested in Conus peptides and their target ion channels. The latter are the key macromolecules underpinning all electrical signals in nervous systems. We use a combination of biochemistry, molecular biology and electrophysiology for our work.

Dale Poulter - My laboratory studies the prenylation and endoproteolytic processing reactions of proteins bearing carboxyl-terminal CaaX sequences, where C is cysteine, a is a small aliphatic amino acid, and X is alanine, serine, methionine, or glutamine. Many of these proteins are involved in signal transduction, including the oncogenic Ras proteins that have been implicated in approximately 30% of human cancers. We work on the enzymology of the modifying enzymes, including overexpression in recombinant organisms, site-directed mutagenesis, and purification, and develop inhibitors based on the chemical mechanisms of the reactions.

Steve Prescott - My laboratory is interested in the regulation of cellular events by lipid messengers. This is an area of signal transduction that affects multiple processes in cell growth, differentiation, and motility - all of which are normal processes that have been corrupted in cancer. Our experiments typically utilized cultured cell systems in which the cells have been genetically engineered to express different genes, and the analysis of responses includes techniques in biochemistry, molecular biology, and cell biology.

Glenn D. Prestwich - My lab studies the role of small molecules, including phosphoinositides, prenylated proteins, and hyaluronic acid -- in cell signaling. We synthesize and develop cellular uses of new biochemical reagents for target identification and active site mapping. The research in our laboratories includes organic synthesis, enzymology, protein isolation and characterization, receptor-ligand binding, radiochemical methods, molecular cloning and protein expression, cell biology, biomaterials preparation and analysis, protein NMR, and fluorescence and plasmon resonance analysis of ligand binding.

Wolfram E. Samlowski - My laboratory performs translational research in cancer immunotherapy. We are interested in evaluating mechanisms of cytokine antitumor activity, especially the induction of nitric oxide as a second messenger. Our current studies are evaluating the mechanism of apoptosis induced by nitric oxide, as well as transcriptional regulation of gene expression by this agent. This laboratory uses cell and molecular biology studies, including DNA microarray analysis to evaluate in vitro mechanisms of transcriptional regulation of genes and apoptosis. These observations are then tested in murine cancer models and in human clinical trials.

Gary C. Schoenwolf - The role of intercellular and intracellular signaling in pattern formation during early embryogenesis. Cell-cell interactions and intracellular signaling play key roles in both normal development and cancer. Cell and molecular biological techniques applied to early chick and mouse embryos.

Katharine Ullman - We are interested in how the process of transport through the nuclear pore takes place. Regulated, bidirectional traffic through this gateway is critical to normal cell function and is a key step in the biogenesis of RNA. To study the nuclear pore, we take advantage of the large oocytes and eggs of the frog, Xenopus laevis, and use a combination of approaches, from in vitro biochemical analysis to in vivo transport studies. Ullman Lab.

David Virshup - Protein phosphorylation is the most widely used signal transduction mechanism. We study the role of phosphorylation in the regulation of nucleocytoplasmic transport, circadian rhythm, and the development of cancer, using a combination of biochemical analysis, and tissue culture and animal models.