GASTROINTESTINAL CANCER RESEARCH GROUP The broad focus of our research is gastrointestinal epithelial pathobiology. Included under this umbrella are molecular mechanisms and chemoprevention of colorectal and liver cancer, host-pathogen interactions/inflammation in the intestine, and intestinal transport in health and disease. These particular areas of focus are of monumental importance to the field of gastrointestinal health and disease. The primary symptom of enteric infection is diarrhea, it is crucial to understand the mechanisms underlying normal physiology of intestinal transport as well as pathogen-induced alterations in this process.
Digestive Disease GI Cancer Researchers
Richard Benya, MD: Dr. Benya's major research focus is on the 7-transmembrane spanning, G protein-coupled (heptaspanning) receptors for gastrin-releasing peptide and for galanin. His ongoing studies for the Gastrin-releasing peptide (GRP) receptor include its role in cancers arising from the GI tract. He is also interested in the role of the galanin receptor in the secretion of chloride from intestinal epithelial cells infected with enteric bacterial pathogens.
Robert Carroll, MD: Dr. Carroll's major research focus concerns the expression and function of gastrin-releasing peptide (GRP) and its receptor. His work shows that these proteins are almost always aberrantly expressed by cancers of the GI tract. When expressed as functional proteins, GRP and its receptor act as morphogens. This work promises to improve the outcome of patients with GI cancers by showing how GRP and its receptor may act to maintain cancers in a well-differentiated state and thereby prevent tumor cell dissemination and metastasis. Clinically his work utilizes magnification and chromendoscopy techniques to identify and assess the earliest premalignant changes in colonic epithelium (aberrant crypt foci). In conjunction with these studies, he works with animal models of GI cancers to identify dietary-gene interactions (chemoprevention) which may influence these lesions.
Sarah Glover, DO: Dr. Glover's research
focus concentrates on how the extracellular matrix (ECM) affects post neoplastic transformation in colon cancer. Preliminary data has shown that cells create an ECM microtopography that changes when individual proteins are modified within cells.
Angela Tyner, PhD: Dr. Tyner studies the intestinal epithelium as a model system for studying cell differentiation and cell turnover. This laboratory has identified a novel epithelial tyrosine kinase call Sik in mice and Brk in humans that is important during gut differentiation. Interestingly, this protein is over-expressed in colon and breast cancers, and Dr. Tyner's lab is attempting to determine how it may influence the behavior of these cancers. The Tyner lab also studies the transcriptional activation of the alpha fetoprotein gene in the liver and small intestine during development, and the role of various cyclin-dependent kinase inhibitors in regulating the cell cycle.
Additional UIC Researchers
Ahsan M. Arozullah, MD: Dr. Arozullah performs health services research with a focus on the impact of literacy and socioeconomic status on racial differences in cancer stage at the time of presentation. He also studies the effect of these factors on the use of and compliance with health care.
Athar H. Chishti, PhD: Dr. Chishti's work focuses on the assembly and regulation of the cytoskeleton. Currently, his lab is investigating the function of MAGUKs (Membrane Associated Guanylate Kinase homologues), a novel family of multidomain proteins that play important roles in cell proliferation and tumor suppression pathways. MAGUKs constitute a family of peripheral membrane proteins composed of PDZ, SH3, and GUK (Guanylate kinase-like) domains. He is interested in the function of p55 (single PDZ domain MAGUK) and human discs large protein, hDlg (with three PDZ domains), in hematopoietic, neuronal, and epithelial cells. Experimental emphasis is on the mechanisms of subcellular targeting, assembly, and trafficking of MAGUKs by utilizing various gene-knockout mouse models.
Robert Costa, PhD: studies the three different hepatocyte nuclear factor 3 (HNF-3) proteins (a, b, g) known to regulate the transcription of liver- and lung-specific genes. The HNF-3 proteins bind to DNA as a monomer through a winged helix motif, also utilized by a number of developmental regulators. Dr. Costa's lab is in the process of analyzing the HNF-3 a and 3 b promoter regions in transgenic animals to determine DNA sequences involved in the establishment of tissue-specific and embryonic expression patterns. He is also interested in the role of the FoxM1B protein in controlling cell proliferations.
Tapas K. Das Gupta, MD, PhD, DSc: In the Department of Surgical Oncology, Dr. Das Gupta is conducting extensive translational research. His current projects include the development of new anticancer drugs from both bacterial and plant sources. His lab has isolated low molecular weight proteins secreted by pathogenic bacteria that have cancer-killing properties. Their ability to control breast cancer and melanoma is under investigation. It is the unique mission of the Department of Surgical Oncology to bring surgical oncologists and basic scientists together to work in proximity and close collaboration.
Alan Diamond, PhD: Dr. Diamond's research interests focus on selenium, an essential trace element currently being considered as a candidate chemopreventive agent. His research is focused on two aspects of selenium biology; how selenium–containing proteins are synthesized and the mechanism(s) by which selenium suppresses cancer. Selenium in protein exists predominantly as the amino acid selenocysteine, which is synthesized on a dedicated selenocysteine tRNA (sec tRNA). Subsequently, sec tRNA recognizes specific UGA codons in mRNA encoding selenoproteins, and the selenium-containing amino acid is added to the growing peptide. The study of the regulation of these proteins, as well as their mechanism of action, are being conducted using animal and cell culture models, as well as human genetics
Alan Feinerman, PhD: Dr. Feinerman's research interests are in the areas of: miniaturization of the scanning electron microscope; linear accelerator/undulator and other analytical instruments; 3D-fabrication techniques. He is currently collaborating with Dr. Sarah Glover, past recipient of T32 support in determining the effect of extracellular matrix texture on cell adhesion as it reltes to metastatic potential.
Andrew Maniotis, PhD: The principal focus of the Maniotis laboratory involves dismantling and reassembling genomes derived from normal and malignant cells. Microsurgical chromatin isolation methods that do not disturb native chromosome structure with detergents, heating, DNA-binding dyes, fixatives, or other harsh chemical or physical treatments, produce chromosome chains that contain all the chromosomes in the genome, arranged as two circular intertwined half-genomes (similar to the Wurfel model proposed). The biochemical and physical mechanisms responsible for structural organization and self assembly of entire genomes in differentiating cells have also been defined with these microsurgically-isolated genomes, revealing a structural memory phenonenon. Structural memory can be observed by reversibly dismantling and reconstituting microsurgically-isolated genomes. Although this "structural memory" or genome self-assembly is only possible because of a still controversial interchromosomal connecting strand of DNA that holds chromosomes in register by their kinetochores as a unified structure, the self-assembly characteristics of the entire genomes with these proteins, and perhaps other proteins that remain to be discovered, is precise to the extent that centromeres appear normal on the reconstituted chromosomes, and 95% of the initial chromosome morphology is restored. He is testing the reconstitution and dynamics of microsurgically isolated genomes under these conditions from cells derived from both normal cells and from malignant human tumors. He hopes to discern fundamental differences relevant to therapeutics among different types of genomes that are responsible for a phenomenon whereby aggressive tumors construct their own perfusion channels independently of tumor angiogenesis.
Debra Tonetti, PhD: Dr. Tonetti's research focuses on the hormonal treatment of breast cancer. Estrogen is known to be essential in the initiation and development of most breast cancers. Tamoxifen is a selective estrogen receptor modulator (SERM) used for the treatment of estrogen receptor positive breast cancers. Dr. Tonetti's research centers on two main areas of hormonal treatment and prevention of breast cancer: 1) the mechanism of tamoxifen-resistant breast cancer, and 2) the interaction of soy and tamoxifen in the prevention of breast cancer. The tamoxifen-resistance project involves a model of tamoxifen-resistant breast cancer established stable overexpression of the enzyme protein kinase C alpha (PKCa) in the T47D human breast cancer cell line. Xenograft tumor models and molecular and cellular techniques are being applied to study a variety of projects including: determining the molecular mechanism of estradiol-induced tumor regression in tumors that overexpress PKCa identification of downstream signals of PKC that may be effective therapeutic targets; examining the role of PKCa overexpression in clinical breast cancer; determining the molecular mechanism of action of combined soy and tamoxifen administration in breast cancer prevention and progression; developing models to study the efficacy of aromatase inhibitors in PKCa overexpressing tumors; and investigating the role of ERß in tamoxifen-resistance.
Terry Unterman, MD: Dr. Unterman is interested in gr owth hormone and insulin-like growth factors. In collaboration with Dr. Robert Carroll, he is examining the role of IGF in colon cancer. He is also interested in the regulation of hepatic gene expression and metabolism by Fox O proteins.
Tatyana A. Voyno-Yasenetskaya, MD, PhD: Dr. Voyno-Yasenetskaya's laboratory is interested in heterotrimeric G proteins, a family of signaling proteins that transduce messages from receptors for extracellular stimuli into cellular responses mediated by effector enzymes or ion channels. Her research focuses on mechanisms of G protein-mediated cell proliferation and programmed cell death (apoptosis). In her laboratory, a variety of approaches are used including the combination of biochemical, cellular, and genetic approaches to investigate the specific signaling pathways leading to G protein-induced mitogenesis or apoptosis and the use of the yeast two-hybrid screening to identify the effector molecules interacting with G proteins. These studies are critical for understanding the control of tissue proliferation and apoptosis and to be able to design novel strategies to control proliferation of cancerous cells.
BACK TO DDN HOME
|
