The behaviors of individual cells within a multicellular organism define its morphology and physiology. Patterns of cell death, cell division, cell migration, and cell communication are critical for normal embryogenesis and for normal function of organ systems. Disturbances in these normal cellular processes are the hallmarks of tumor cells. In order to decipher what goes wrong in a cancer cell and, ultimately, to be able to intervene with rational therapies, it is critical to understand the molecular mechanisms underlying these fundamentally important cellular processes.

Investigators within the Huntsman Cancer Institute are probing many central features of a cell's behavior: how cells move, how they proliferate, how they communicate with each other, how they organize their internal components, how they maintain homeostasis. The environment fosters collaborative efforts among laboratories and encourages students to obtain broad training. Interdepartmental research groups meet regularly to share recent developments and discuss common scientific interests. Several advanced classes that focus on the molecular basis of cancer and signal transduction provide rigorous formal training. Opportunities to acquire experience in advanced research technologies such as digital image analysis are available on campus. In addition, small workshops that focus on areas of keen interest to cancer researchers, such as mitosis, cell motility, tumor-suppressors, and growth factors are offered. The infrastructure for research in cell biology is outstanding, with state-of-the-art light and electron microscopes and core facilities for the generation of transgenic and knock-out animals, peptide synthesis and sequencing, protein interaction, flow cytometry, mass spectrometry, cytogenetics, and many other applications.

Participating Faculty

Rick Ash - My laboratory is interested in the relationships between amino acid transport and cellular physiology. We are discovering linkages between glutamate transport and glutathione metabolism. We use somatic cell genetics, biochemistry and molecular biology to study mammalian cell culture models.

Michael Bastiani - The lab studies the molecular regulation of neuronal growth cone behavior during brain development and in particular the role of lipocalins. "Unregulated" cancer cell motility is a key behavior leading to tumor metastisies. We study the dynamic behaviors of growth cones primarily in C. elegans using state of the art confocal microscopic imaging techniques, but also make extensive use of molecular and genetic techniques in Drosophila and mouse to study molecular function.

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.

Chi-Bin Chien - My lab is studying axon guidance, using the retinotectal projection of zebrafish as a model system. How axons find their initial targets in vivo is a basic problem of developmental neurobiology, which we are attempting to address at a cell biological level. We are using a combination of molecular biology, classical genetics, positional cloning, and sophisticated imaging methods to define the molecules involved in retinal axon guidance and how they control growth cone dynamics.

Maureen L. Condic - We are interested in the control of neuronal fate and axon outgrowth during development of the nervous system. The control of cell fate and cell migration are important topics both in developmental biology and in cell biology. We work in embryonic animal models (chicks, rats and mice), both in vitro and in vivo, using cell biological and molecular biological 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.

Susan Mango - Our lab is interested in the mechanisms that underlie organogenesis, including cell fate determination and morphogenesis. We study i)how the PHA-4 transcription factor specifies different cell fates within the C. elegans digestive tract during development and ii)how cell shape changes enable a cluster of precursor gut cells to develop into a linear digestive tube. We use genetics, experimental embryology and molecular approaches with C. elegans, a small, free-living nematode. Mango Lab.

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.

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.

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.

Janet Shaw - The Shaw lab studies the molecular basis of mitochondrial dynamics in eukaryotic cells. Changes in mitochondrial morphology and metabolic activity are associated with some cancers and could contribute to the uncontrolled growth of tumorigenic cells, or could be an indirect (and possibly diagnostic) consequence of cellular transformation. Using yeast as a model organism and a combination of genetic, molecular and cell biological techniques, we have identified proteins that control mitochondrial fission and fusion, mitochondrial transport during division, and mtDNA maintenance.

Gerald Spangrude - The Spangrude laboratory is interested in defining the cellular events that lead to blood development (hematopoiesis) in mammals. Hematopoiesis is a developmental program that persists after birth and continues throughout the life of mammals, and is regulated by cytokines, cell-cell interactions, and apoptotic mechanisms. We use flow cytometry, cell culture, and transplant models in the mouse to define cell populations that are critical to hematopoiesis and bone marrow transplantation.

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.

Janis J. Weis - My laboratory is interested in the inflammatory mechanisms involved in Lyme arthritis development. We study the interaction of Borrelia burgdorferi lipoproteins with toll-like receptor 2 in mammalian cells. We use in vitro systems to analyze the responses leading to arthritis, and we are identifying by quantitative trait loci the genetic elements which regulate arthritis severity in mice.

John H. Weis - Focus is on role of the innate immune response using molecular genetic tools to dissect the studies of allergy, inflammation, bone marrow development and immune cell activation. Our work concentrates on role of mast cell and products, B cell expression and maturation, and bone marrow development in the immune response coupled with concentration upon novel gene discovery. Focus is on using genetic constructs to create novel cell and animal responses to immune assault.

H. Joseph Yost - Our research group is interested in the developmental genetic pathways and mechanisms that establish the vertebrate body plan. We use embryos of zebrafish and the frog Xenopus laevis in complementary approaches, with a focus on how left-right asymmetry is established in the embryo and transmitted to brain, heart and viscera primordial cells. The projects in the lab encompass a broad range of molecular and cell biological topics, including cell-matrix and cell-cell interactions, cell fate and migration, cell signaling pathways from ligand/receptors interactions to transcription co-factors and RNA translational control. Yost Lab.