Our laboratory studies an amazing regulatory factor known as NF-kappaB. This transcription factor controls key developmental and immunological functions and its dysregulation lies at the heart of virtually all major human diseases.
Metabolism and disposition of xenobiotics in vivo and in vitro: isolation, identification, characterisation and quantitation of radioactive and unlabelled metabolites and DNA adducts. Enzymology of mixed-function-oxidase-dependent reactions. Toxicology of food additives, contaminants and environmental pollutants. Genotoxicity, mutagenicity and DNA binding of polycyclic aromatic hydrocarbons and nitrosubstituted arenes, and of water disinfection products.
We study the interface between signal transduction and cell function. Approaches employed include - molecular genetics, protein and lipid biochemistry, confocal and electron microscopy, protein crystallography, and model organisms approaches (e.g. yeast, Arabidopsis, C. elegans, mouse gene knockout technology).
Coronaviruses, including SARS and Noroviruses are used as models to study the genetics of RNA virus transcription, replication, persistence, cross species transmission and vaccine development.
Blood vessel formation in cancer and development; use mouse culture (stem cell derived vessels) and in vivo models (embryos and tumors); genetic, cell and molecular biological tools; how do vessels assemble and pattern?, dynamic image analysis.
We study the cell biology of the protozoan parasites that cause Toxoplasmosis and Malaria, especially the mechanism and control of parasite motility and host cell interaction.
Dr. Belger's research focuses on studies of the cortical circuits underlying attention and executive function in the human brain, as well as the breakdown in these functions in neuropsychiatric and neurodevelopment disorders such as schizophrenia and autism. Her research also examines changes in cortical circuits and their physiological properties in individuals at high risk for psychotic disorders. Dr. Belger combines functional magnetic resonance imaging, electrophysiological scalp recording, experimental psychology and neuropsychological assessment techniques to explore the behavioral and neurophysiological dimensions of higher order executive functions. Her most recent research projects have begun focusing on electrophysiological abnormalities in young autistic children and individuals at high risk for schizophrenia.
Research interests include atherosclerosis, thrombosis and von Willebrand's disease. The role of von Willebrand factor in arterial thrombosis is being studied in atherosclerotic vessels to gain a better understanding of thrombosis and its possible prevention in people with coronary artery disease. Comparative pathology and the use of animal models in research are also the focus of some research efforts.
We study interactions of proteins and peptides with membranes. Specifically we study the interaction of the A-beta peptide with lipids in the membrane. It is well known that Alzheimer’s is an aggregation disorder with A-beta being the aggregating species. However, it is unknown what initiates this aggregation. Experimental evidence has shown that A-beta peptides will undergo a conformational change to an aggregate structure when interacting with surfaces of certain lipid membranes. It is of interest to our group to understand what causes this conformational change and what properties of lipids most promote this effect.
We also study structural and dynamical properties of biomembranes containing cholesterol. The goal of our research on structural and dynamical properties of membranes containing cholesterol is to gain knowledge about the nature of phospholipid-cholesterol interactions that play an important role in functioning of membranes, in cell communications and in formation of domains called lipid rafts. Detailed knowledge of the membrane properties helps us to understand the normal functioning of cells and it is instrumental in the search for a cure from a large variety of diseases. We use computer simulation techniques to perform our studies. Member of the Molecular & Cellular Biophysics Training Program
The goal of our laboratory is to investigate mechanisms of tumorigenesis and tumor progression, and to apply genome-wide techniques to develop anti-cancer therapies. Our research focuses on transcriptional regulation of gene expression during stem cell self-renewal and differentiation and during tumorigenesis. We use artificial transcription factors (ATFs) as genetic probes to identify genes and gene pathways responsible for the appearance of specific malignant phenotypes and we investigate the ability of these ATFs to interfere with tumor cell regulatory programs. Cancer cell reprogramming with such artificial “genetic switches” may afford a new therapeutic strategy.
Our objective is to understand the dynamic and structural properties of chromosomes during mitosis. We use live cell imaging techniques to address how kinetochores are assembled, capture microtubules and promote faithful segregation of chromosomes.
My lab uses a cognitive neuroscience approach to understand the neurobiology of drug addiction in humans. The tools we use include fMRI, cognitive testing, physiological monitoring, pharmacology, and genetic testing. We specifically seek to determine 1) how the brain learns new stimulus-response associations and replaces learned associations, 2) the neurobiological mechanisms underlying the tendency to select immediate over delayed rewards, and 3) the neural bases of addiction-related attentional bias.
Our long term goal is to define the molecular mechanisms of two-component regulatory systems, which are utilized for signal transduction by bacteria, archaea, eukaryotic microorganisms, and plants. Our current focus is to understand the features that control the rates of self-catalyzed phosphorylation and dephosphorylation of response regulator proteins. The kinetics of these reactions vary dramatically (>40,000x) between different pathways and reflect the need to synchronize biological responses (e.g. behavior, development, physiology, virulence) to environmental stimuli. Member of the Molecular & Cellular Biophysics Training Program
I am collaborating with Dr. Rosann Farber on molecular mechanisms of microsatellite instability. Microsatellites are repetitive DNA sequences in which the number of bases in a repeat unit can number from 1-6 bases. Microsatellites are widely dispersed throughout the eukaryotic genome and there are differences in the numbers of repeats among alleles. These sequences are exceptionally unstable in cells lacking mismatch repair. We have developed a selective system in which to measure mutation rates in microsatellites in cultured cells. Using this system we can compare mutation rates and mutation spectra in normal and neoplastic cells and cells with or without mismatch repair. Much of our research has focused on the properties of microsatellites that may affect their mutation rate. These include: 1) length of the repeat unit (e.g., mono- vs. dinucleotides), 2) base composition of the repeat, 3) number of repeat units per tract, 4) degree of perfection of repeats (i.e., presence or absence of interruptions in the tract), and 5) composition of flanking sequences.
This multidisciplinary laboratory has 6 interests: 1) Defining regionally specific adaptations responsible for functions altered by chronic ethanol; 2) Characterizing regional CNS biochemical changes induced by stress and CRF after chronic ethanol; 3) Defining the role of central cytokines in behaviors induced by stress; 4) Exploring how a benzodiazepine (BZD) agonist shares actions with a BZD antagonist; 5) Defining TRH receptor subtype(s) responsible for its anti-anxiety and analeptic actions; and 6) Defining the action of galanin on ethanol withdrawal-induced anxiety. To undertake our interests, behavioral, anatomical, pharmacological, electrophysiological, biochemical, and molecular biological approaches are used.
The Brenman lab studies how a universal energy and stress sensor, AMP-activated protein kinase (AMPK) regulates cellular function and signaling. AMPK is proposed to be a therapeutic target for Type 2 diabetes and Metabolic syndrome (obesity, insulin resistance, cardiovascular disease). In addition, AMPK can be activated by LKB1, a known human tumor suppressor. Thus AMPK signaling is not only relevant to diabetes but also cancer. We are interested in molecular genetic and biochemical approaches to understand how AMPK contributes to neurodegeneration, metabolism/cardiac disease and cancer.
We are interested in the mechanism by which eukaryotic cells are polarized and the role of vesicle transport plays in the determination and regulation of cell polarity and tumorigenesis.
Research in the Brouwer laboratory is focused on: (1) hepatobiliary xenobiotic disposition, including mechanisms of hepatic uptake, translocation and biliary excretion; (2) development/refinement of in vitro model systems to predict in vivo hepatobiliary disposition, drug interactions, and hepatotoxicity; (3) hepatic drug transport; and (4) pharmacokinetics, including aberrant gastrointestinal drug absorption phenomena.
Our lab is interested in the role of chromatin-modifying factors and epigenetics in mammalian development and disease. We are particularly interested in two major areas both of which make use of mouse models: (1) the role of BRG1 and SWI/SNF nucleosome-remodeling complexes in various aspects of hematopoiesis including regulation of globin gene expression and inflammation; (2) the role of dietary fiber and gut microflora on histone modifications, CpG methylation, and prevention of colorectal cancer.
Experimental Evolution of Viruses. We use both computational and experimental approaches to understand how viruses adapt to their host environment. Our research attempts to determine how genome complexity constrains adaptation, and how virus ecology and genetics interact to determine whether a virus will shift to utilizing new host. In addition, we are trying to develop a framework for predicting which virus genes will contribute to adaptation in particular ecological scenarios such as frequent co-infection of hosts by multiple virus strains. For more information, and for advice on applying to graduate school at UNC, check out my lab website www.unc.edu/~cburch/lab.
Cell adhesion, both to other cells and to ECM, signaling, the cytoskeleton and cell migration. The Rho family of GTPases, their regulation by guanine nucleotide exchange factors and GAPs. Inflammation and leukocyte transendothelial migration.
