Tight junctions are intercellular contacts that form a barrier required for ion transport and organization of cell polarity. Our lab investigates assembly and regulation of TJ proteins and the molecular basis for ion selectivity in epithelia.
We study arterioles that vascular resistance in healthy kidneys and kidneys of genetic hypertensive animals or those with mutated selected genes. Measurements include renal vascular reactivity in vivo and receptor/calcium signaling in vitro.
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).
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.
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.
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.
It has been postulated for some time that cellular transplantation to the liver might allow for the reversal of hepatic based genetic defects or augmentation of hepatocellular function. However, the identification of the proper cell type and transplant conditions to produce liver engraftment and normal hepatocyte function has remained elusive. We have developed an alternative strategy using embryonic stem (ES) cells differentiated /in vitro/ and transplanted into hepatic parenchyma as “gene vectors” in order to restore wild type hepatocellular function.
Research in the Carelli laboratory is in the area of behavioral neuroscience. Our studies focus on the neurobiological basis of motivated behaviors, including drug addiction. Electrophysiology and electrochemistry procedures are used during behavior to examine the role of the brain 'reward' circuit in natural (e.g., food) versus drug (e.g., cocaine) reward. Studies incorporate classical and operant conditioning procedures to study the role of the nucleus accumbens (and dopamine) and associated brain regions in learning and memory, as they relate to motivated behaviors.
Gene targeting and state-of-the-art phenotyping methods are used to elucidate the reproductive and cardiovascular roles of the adrenomedullin system and to characterize the novel GPCR-signaling mechanism of Adm’s receptor and RAMP’s.
Our research centers on the cell biology and biochemistry of motor proteins and the cytoskeleton and their roles in processes such as cell crawling, phagocytosis, organelle transport.
Steroid hormones regulate tissue-specific gene expression in animals via receptor dependent intracellular signal transduction pathways. We are particularly interested in glucocorticoid receptors and their actions on the immune system because they reflect the primary response to environmental stress. Current research projects are examining the following aspects of glucocorticoid hormone action. A second major interest of the laboratory focuses on evaluating the mechanisms involved in the regulation of apoptosis in normal and neoplastic cells. Research is aimed at the identification and cloning of genes that are responsible for both the initiation and execution of apoptosis.
Cross-talk between insulin like growth factor -1 and cell adhesion receptors in the regulation of cardiovascular diseases and complications associated with diabetes
Dr Costa's primary research interests focus on the potential for air pollutants to adversely affect human health. By using animal models representing healthy and susceptible human populations (chronic heart and lung diseases), he has made major in-roads into understanding how contaminants in the air can cause illness and even death. He uses methods in cardiopulmonary and neuro-physiology coupled with modern cell-molecular biology to develop these models and to ascertain how health impairments influence responsiveness to pollutant stresses.
Cellular and molecular basis of the mucociliary clearance system in the airways of the lung. Our focus is on the regulation of mucin secretion and ciliary activity at the cell and molecular levels.
My interests focus on developing quantiative methods to assess the relationships between exposure, dose and response. This research has examined methods for dioxins, thyroid hormone disruptors and pyrethroid pesticides.
This lab studies vascular biology and physiology, with specific focus on the signaling mechanisms directing 1) normal adaptive and pathological growth of the vascular wall, 2) arteriogenesis (formation of collateral vessels) in models of tissue ischemia.
As the Director of the UNC Kidney Center, the scope of Dr. Falk's research interests spans many disciplines, including
molecular biology, immunology, genetics, pathology, cell biology, protein chemistry, epidemiology, pharmacokinetics and biostatistics. Dr. Falk is recognized world wide as a leader in research on kidney diseases related to autoimmune responses. He works closely with the basic research scientists within the UNC Kidney Center, including Dr. Gloria Preston, thus this research program provides an environment for Translational Research within the UNC Kidney Center.
The research program of Dr. Fischer focuses on three closely related areas. Mechanisms for atherogensis, processes of platelet-mediated hemostasis and mechanisms for surface hemostasis.
We study intracellular trafficking of the chloride channel CFTR in heterologous systems and in primary human airway epithelial cultures. The most common mutation in cystic fibrosis, deltaF508, results in a misassembled protein that is retained at the ER but can escape and proceed to the plasma membrane by addition of small molecule correctors or low temperature incubation. Temperature-rescued deltaF508 disappears rapidly from the cells surface and is subjected to lysosomal degradation, while wild-type CFTR is recycled back to the plasma membrane. Of particular interest is the mechanism that leads to elimination of detlaF508 from the cell surface.
We are interested in how complex signaling systems interact to preserve homeostasis, while also optimizing the response of the organism to environmental changes. Two different projects are ongoing in the laboratory: Project 1: Matching renal salt excretion with dietary salt intake is vital for survival. We are integrating whole animal physiological studies and innovative molecular techniques to investigate the role of a new intestinal hormone, uroguanylin, in this process. Project 2: How do target organs communicate with neural circuits? We are investigating feedback regulation of a simple neural circuit that uses a novel form of muscle-to-nerve communication to control the contractions of the heart musculature.
Our lab is studying the role of mitogen and stress-activated protein kinases to regulate key aspects of cell metabolism. We are also studying signalling by tyrosine kinases in response to toxicological agents or cell stress.
Research in my laboratory focuses on how animals produce and control movement, with a particular interest in animal flight. We use both computational and experimental techniques to examine how organismal components such as the neuromuscular and neurosensory systems interact with the external environment via mechanics and aerodynamics to produce movement that is both accurate and robust. Keywords: biomechanics, flight, avian, insect, neural control, muscle, locomotion, computational modeling
Our research focuses on understanding the molecular and cellular mechanisms of leukocyte (white blood cell) trafficking and homing in vascular inflammation and immune responses. We are interested in the glycobiology of the Selectin leukocyte adhesion molecules and their ligands, and understanding the roles for these glycoproteins in the pathogenesis of inflammatory/immune cardiovascular diseases such as atherosclerosis and vasculitis. We are also interested in the mechanisms whereby the selectins and their ligands link the inflammatory response and coagulation cascade and thereby modulate thrombosis and hemostasis.
We are studying how hemangioblasts, a bipotential precursor of endothelial and hematopoietic lineages, are specified and differentiated during development using zebrafish as a model system.
I am interested in the comparative biomechanics of marine invertebrates. In particular, I study the functional morphology of musculoskeletal systems, the structure, function, development and evolution of muscle, and invertebrate zoology, with particular emphasis on the biology of cephalopod molluscs (octopus and squid). My research is conducted at a variety of levels and integrates the range from the behavior of the entire animal to the ultrastructure and biochemistry of its tissues.
Dr. Maixner’s research program focuses on identifying the pathophysiological processes that underlie pain perception, persistent pain conditions, and related disorders. His current research focuses on genetic, environmental, biological, and psychological risk factors that contribute to the onset and maintenance of chronic pain conditions. A long term goal of his program is to translate new discoveries into clinical practices that improve the ability to diagnose and treat patients experiencing chronic pain.
We study genetic controls of vascular development in mouse and chick models. Current projects focus on the roles of sonic hedgehog and transcriptional silencers in control of vascular stem and progenitor cell differentiation. Other ongoing projects examine the role of notch signaling in coronary artery development, and explore the link between cytoskeletal remodeling and transcriptional activation in smooth muscle differentiation.
Physiology and pharmacology of the basal ganglia; neurobiology of motivation and reward; substance abuse neurobiology; and neurobehavioral teratology.
My laboratory studies the function of neural circuitry involved in the perception of reward and the reinforcement of motivated behaviors in several mouse models of neurodevelopmental disorders, including early developmental exposure to drugs of abuse, such as alcohol or cocaine; and genetic models relevant to the study of autism, such as inactivation of the Fmr1 (Fragile-X Mental Retardation) or MeCP2 (Methyl-CpG Binding Protein) genes. My laboratory employs techniques in behavioral pharmacology, including intracranial self-stimulation (ICSS); in vitro patch-clamp electrophysiology in acute brain slices; and immunohistochemistry with unbiased stereological microscopy.
Our interest lies in the understanding of mechanisms involved in adaptation and restitution of function of striated muscle during development, injury and disease states. Regeneration of striated muscle including cardiac tissue and skeletal muscle is being actively sought with the use of various types of stem cells from various origin. We are investigating the mechanisms that control adult-derived stem cells to aquire a cardiac phenotype.
Our laboratory studies the mechanisms of sensory information processing in the nervous system, with an emphasis on processing in the auditory pathways. We study the role of ion channels in integration at the single cell level, short and long-term synaptic plasticity, synaptic function, and ion channel dynamics in the auditory brainstem and auditory cortex. We are also studying how different kinds of hearing loss affect central auditory function. Experimentally, we use patch clamp (current, voltage and dynamic clamp) methods in brain slices, live optical imaging of activity, a variety of biochemical and molecular methods, mice with genetic hearing loss, noise-induced hearing loss, auditory brainstem evoked response, and acoustic startle response to evaluate hearing function in animal models. The laboratory extensively utilizes quantitative experimental techniques, complemented with detailed computational modeling at the single cell and network levels to further understand the normal information processing capacity of auditory neurons, and the consequences of changes in ion channel and synaptic function after hearing loss.
The goal of the laboratory’s research is to define the structure and function of an intracellular Ca2+ release channel in skeletal and cardiac muscle, using molecular biological and electrophysiological methods and by creating mutant mice.
We are identifying genetic variants that influence common human traits with complex inheritance patterns, and we seek to understand the biological function of the identified variants. Currently we are investigating susceptibility to type 2 diabetes and obesity, as well as variation in cholesterol levels, blood pressure, body size, weight gain and early growth. In addition to examining the primary effects of genes, the lab is exploring the interaction of genes with environmental risk factors in disease pathogenesis. Approaches include genome-wide association studies, genetic epidemiology, resequencing, bioinformatic analysis, molecular biology, cell biology, and mouse models to compare high- and low-risk alleles in a whole-animal setting.
Fertilization leads to the formation of a new diploid individual and represents an exquisite example of the specificity of cell to cell and cell surface-extracellular matrix interaction. Our research laboratory is interested in the study of the structure and function of sperm proteins. The long-term goal of our research is to define a set of sperm molecules that are necessary for one or more steps in the fertilization process. A full understanding of the mechanisms of sperm maturation and fertilization would allow precise targets for both infertility diagnosis and contraception.
Currently, the structure and function of two different proteins are under study. These proteins are: 1) NASP a nuclear protein that binds and transports linker histones into the nucleus and is critical for mitosis and meiosis; 2) Eppin a testis and epididymal serine protease inhibitor.
An important step in the development of tests for the diagnosis of infertility and for the development of a male gamete based contraceptive is the determination of specific protein-protein interactions that are necessary for fertilization. Characterization of these interactions will
provide sites for contraceptive development.
The Patterson laboratory has 4 major focuses, each of which is funded by at least one major grant. Our longest ongoing project focuses on blood vessel growth and development, and in particular how bone morphogenetic protein signaling regulates vascular development. A second ongoing project in the laboratory is to understand at a fundamental level the cellular response to proteotoxic stress. The third major focus of our laboratory studies cardiac-specific ubiquitin ligases that regulate cardiac hypertrophy and metabolism. Finally, we have begun a human translational study that takes advantage of our expertise in genomics, proteomics, and genetics to develop an integrated DNA/RNA/protein profile database of patients with heart disease.
My laboratory, located in the Cystic Fibrosis/Pulmonary Research and Treatment Center in the Thurston-Bowles building at UNC, is interested in how respiratory viruses infect the airway epithelium of the conducting airways of the human lung.
Dr. Pomp studies the genetic architecture of complex traits, with an emphasis on body weight regulation and obesity. Using polygenic mouse models and high throughput approaches integrating genomics and physiology, he identifies genes that control predisposition to a variety of complex traits including energy intake and energy expenditure (e.g. voluntary exercise). In addition, Dr. Pomp studies how these genes interact with each other, with changing environments such as nutritional interventions, and with other diseases such as cancer.
Two dynamically interacting sets of mechanisms govern tissue-specific gene expression and cell growth. 1) mechanisms in lineage biology regulate stem cells and their descendents, processes that define the repertoire of genes available to be regulated and 2) signal transduction mechanisms, induced by the synergistic effects of extracellular matrix components and soluble signals (hormones, growth factors), regulate the expression of the available genes. Studies in the lab focus on both classes of mechanisms in normal versus neoplastic tissue.
My interests include the use of immunological and molecular probes to study function of normal and abnormal coagulation factors; the study of factors regulating human immune response to coagulation factors; and immunochemical studies of antigen-antibody interaction.
The nucleus accumbens is a limbic-motor integrator, assimilating memory and drive input and coordinating responsive behavioral output. Anatomical and pharmacological evidence indicates that the core and shell subregions of the nucleus accumbens perform overlapping but distinct roles in motivated behavior. My experiments examine nucleus accumbens core and shell function during ethanol drinking behavior in rats, with particular focus on how dopamine input modulates accumbal activity on the millisecond timescale. I use two approaches: electrophysiological firing patterns of neurons in the nucleus accumbens core and shell are evaluated using multi-electrode arrays, and phasic (subsecond) dopamine activity is evaluated using fast-scan cyclic voltammetry. I am also interested in exploring the pharmacological manipulation of neuronal transmission in the nucleus accumbens, focusing on drugs that have clinical therapeutic value in treating alcoholism.
Ion channels and ionotropic receptors. Molecular mechanisms of ligand binding, channel activation, ion selectivity, and allosteric modulation. Techniques used: Molecular modeling, site directed mutagenesis, heterologous expression in Xenopus oocytes and other cells, chemical modification, and voltage clamp electrophysiology.
Our laboratory is involved in studies to determine the mechanisms and proteins involved in the migration of alloreactive and regulatory T cells to organs involved in graft-versus-host disease after stem cell transplantation using mouse models.
Dr. Smith’s research interests are in correlating pharmacokinetics and metabolism of drugs with their pharmacodynamics and toxicity. Research efforts in this area include in vitro studies and in vivo animal experiments aimed at understanding mechanisms of processes that influence drug disposition and toxicity. Where possible, transitional studies in human subjects are conducted to demonstrate clinical relevance and the potential application to humans. A primary emphasis in the laboratory is the process of glucuronidation, the major Phase II metabolic pathway where the sugar, glucuronic acid, is coupled to drugs and other xenobiotics.
Work in my laboratory is directed at the role of neuronal growth factors in the development and regeneration of axons. We employ sensory neurons of the DRG as a model system. Sensory neurons are unique in elaborating a peripheral axon that regenerates readily after injury and a central axon projecting in the spinal cord that does not. This work is directly relevant to a major NINDS goal of achieving spinal cord repair.
I study the ultimate and proximate factors controlling flexibility in reproductive behavior. Using songbirds as a system, I use field and laboratory studies to investigate the ecological cues regulating reproductive flexibility, the neural integration of these cues, and the neural mechanisms precipitating adaptive behavioral outcomes. Of particular interest is the study of courtship and mate-choice behavior and how the songbird brain integrates ecological and social information. I am also interested in how the timing of reproduction, reproductive effort, and family planning are controlled. I use high performance liquid chromatography for the measurement of central catecholamines and immunocytochemistry and microscopy for quantifying neuropeptides and the expression of immediate early genes as markers of neural activity.
Research interests involve metabolic interactions of essential microelements, especially trace metals, with toxic metals and metalloids that contaminate food chain and drinking water reservoirs. Research topics include: the interactions between selenium, an essential micronutrient, and arsenic, an environmental contaminant and human carcinogen; the enzymes and co-factors involved in the metabolism of arsenic and selenium; the mechanisms of arsenic- induced diabetes; and, the role of nutritional antioxidants and antioxidant enzymes in responses to the oxidative stress induced by exposure to environmental toxins, by viral infections or nutritional deficiencies.
The mechanical properties, force response and force generating mechanisms of biological systems is of great interest for physiological function, for tissue engineering and embryogenesis and for drug delivery. In collaboration with the Computer Science Department, we develop and apply new technologies for applying and measuring forces on single molecules, cells and tissue cultures. In collaboration with the departments of Mathematics, Computer Science, Chemistry and the UCN Cystic Fibrosis Center we are pursuing an integrated computational model of mucus clearance in the lung. Affiliated with the Molecular & Cellular Biophysics Training Program.
A critical component of airways innate defense is the thin liquid layer lining airway surfaces, the periciliary liquid (PCL), that provides a low viscosity solution for ciliary beating and acts a lubricant layer for mucus transport. Normal airways appear to be able to sense the PCL volume and adjust ion channel activity accordingly. The long term goal of this laboratory is to understand how homeostasis of PCL volume occurs in airway epithelia under normal and pathophysiological conditions. Currently, research in the Tarran lab is focused on three main areas: 1) Regulation of epithelial cell function by the extracellular environment, 2) Gender differences in cystic fibrosis lung disease and 3) The effects of cigarette smoke on epithelial airway ion transport. We utilize cell biological and biochemical techniques coupled with in vivo translational approaches to address these questions.
My primary research interests are directed at the neurobiology of alcoholism. To study the central mechanisms involved with neurobiological responses to ethanol, I use both genetic and pharmacological manipulations. There are many factors that may cause an individual to progress from a moderate or social drinker to an alcoholic. In addition to environmental influences, there is growing evidence in both the human and animal literature that genetic factors contribute to alcohol abuse. Furthermore, the risk for developing alcoholism is likely not associated with a single gene, but rather with multiple genes that interact with environmental factors to determine susceptibility for uncontrolled drinking. Some of the questions that my laboratory is currently addressing are: 1) Does central neuropeptide Y (NPY) signaling modulate neurobiological responses to ethanol and ethanol consumption, 2) Do melanocortin peptides modulate ethanol intake? and 3) Does cAMP-dependent kinase (PKA) play a role in voluntary ethanol consumption and/or other effects produced by ethanol?
The genetic pathways for the development of cardiac and vascular smooth muscle cells. In particular, the transcriptional control of mammalian cardiovascular system, and cell proliferation and differentiation-related human cardiovascular disorders.
I’m a neurobiologist who uses immunocytochemistry and electron microscopy to address functional questions. I am trying to elucidate the molecular organization of postsynaptic signaling in the rat cortex and hippocampus. I'm also interested in the actin cytoskeleton of dendritic spines, and how spines may remodel during LTP.
Construction of chimeric antithrombotic proteins targeted to endothelial cell surfaces; Activity of these using in vitro assays and in vivo mouse models of arterial and venous thrombosis; pathophysiology of hemostasis/thrombosis in these mouse models.
My lab concentrates on studying the molecular genetic basis of the evolutionary processes of adaptation and speciation. The questions we ask are what are the sequence changes that lead to variation between species and diversity within species, and what can these changes tell us about the processes that lead to their evolution. We use a number of different techniques to answer these questions, including molecular biology, sequence analyses (i.e. population genetics and molecular evolution techniques), physiological studies, and examinations of whole-organism fitness. Currently work in the lab has focused on a intertidal copepod species that is an excellent model for the initial stages of speciation (and also provides opportunities to study how populations of this species adapt to their physical environment).
We investigate the role of cardiac specific proteins (Muscle Ring Finger or MuRF proteins) that regulate glucose and fatty acid metabolism, cardiac muscle mass, and sarcomere protein metabolism in the context of common cardiac diseases. Recently, we have identified that MuRF proteins have ubiquitin ligase activity, which enables them to interact with specific proteins, post-translationally modify them with ubiquitin, and subsequently target them for degradation. We focus on mouse models of disease using transgenic and knock-out mice, integrating cardiac physiology with several imaging modalities including echocardiography, Doppler, and SPECT. Since several of the models we have created involve developmental defects, we investigate in utero cardiac function and signaling pathways
with this state of the art of imaging. Our overall goal is to determine how the ubiquitin proteasome system specifically regulates the heart at the molecular level and determine how this affects cardiac function, in order to
translate these findings into therapies & diagnostics for common cardiac diseases such as heart failure and myocardial infarction.
We recently found that nociceptive (pain-sensing) circuits in mammals are highly organized at molecular and neuroanatomical levels. In our laboratory, we are using molecular, genetic, electrophysiological and behavioral approaches to study these pain circuits in mice. Our ultimate goal is to identify new analgesics so that debilitating chronic pain conditions can be more effectively treated.
Techniques used in our lab include: Molecular biology and cell culture; In situ hybridization and immunofluorescence staining; Construction and characterization of knock-in and transgenic mice; Mouse behavioral experiments; Bioinformatics; FACS of neurons; Expression profiling with
Affymetrix GeneChip arrays; Calcium imaging; Patch Clamp Electrophysiology.
