Our research group utilizes the nematode C. elegans to investigate germ cell immortality: mechanisms that allow germ cells remain eternally youthful as they are transmitted from one generation to the next. We also study how telomerase functions at chromosome termini, as well as the consequences of telomere dysfunction.
Research is aimed at evaluating genetic and epigenetic mechanisms in environmental chemical carcinogenesis. Specific project areas are concerned with toxicity assessments of conazole pesticides, arsenic, and water
disinfection by-products. Human and rodent cells are analyzed for chemical-induced alterations in DNA
methylation and gene expression in combination with chromosome damage, cell toxicity and histopathological
effects. Ultimate goals are to improve the scientific basis of risk assessment, and include evaluations of lifestage
and nutritional susceptibility risk factors which may modulate chemical toxic/carcinogenic effects.
My research focuses on developing biologically based models for the uptake, distribution, metabolism, and biological effects of drugs and chemicals and their application to safety assessments and quantitative health risk assessments. In recent years, my research emphasis has been on developing mathematical descriptions of control of genetic circuitry and the dose-response and risk-assessment implications of these control processes.
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.
Laminar organization of neurons in cerebral cortex is critical for normal brain function. Two distinct cellular events guarantee the emergence of laminar organization-- coordinated sequence of neuronal migration, and generation of radial glial cells that supports neurogenesis and neuronal migration. Our goal is to understand the cellular and molecular mechanisms underlying neuronal migration and layer formation in the mammalian cerebral cortex. Towards this goal, we are studying the following three related questions:
1. What are the signals that regulate the establishment, development and differentiation of radial glial cells, a key substrate for neuronal migration and a source of new neurons in cerebral cortex?
2. What are the signals for neuronal migration that determine how neurons reach their appropriate positions in the developing cerebral cortex?
3. What are the specific cell-cell adhesion related mechanisms that determine how neurons migrate and coalesce into distinct layers in the developing cerebral cortex?
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.
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.
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.
Current research projects in the Campbell laboratory include structural, biophysical and biochemical studies of wild type and variant Ras and Rho family GTPase proteins, as well as the identification, characterization and structural elucidation of factors that act on these GTPases. Ras and Rho proteins are members of a large superfamily of related guanine nucleotide binding proteins. They are key regulators of signal transduction pathways that control cell growth. Rho GTPases regulate signaling pathways that also modulate cell morphology and actin cytoskeletal organization. Mutated Ras proteins are found in 30% of human cancers and promote uncontrolled cell growth, invasion, and metastasis. Another focus of the lab is in biochemical and biophysical characterization of the cell adhesion proteins, focal adhesion kinase, vinculin, paxillin and palladin. These proteins are involved in actin cytoskeletal rearrangements and cell motility, amongst other functions. Most of our studies are conducted in collaboration with laboratories that focus on molecular and cellular biological aspects of these problems. This allows us to direct cell-based signaling, motility and transformation analyses. Member of the Molecular & Cellular Biophysics Training Program.
The Cancer Biology Group at NIEHS focuses on early events in skin tumor development using a transgenic mouse model (TgAC). This model possesses a v-Ha-ras transgene under the regulation of a fetal globin promotor integrated at an ectopic site which confers a unique phenotype of inducible skin papillomas with a high rate of progression to invasive squamous and spindle cell neoplasms. The goals of our studies are to identify and characterize: 1) The cellular origin of the tumors and 2) critical genes which are involved in ras-mediated tumor induction and progression. Conventional cancer therapies have until recently depended on treatment late stages of tumor growth and involved non-specific mechanisms of cellular injury. By focusing on understanding early events in tumor induction we hope to gain insights into targets for intervention that can more specifically inhibit cancer cell growth.
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.
This laboratory has worked for over 25 years investigating both fundamental and clinically relevant aspects of ciliary and flagellar motility in eukaryotic cells. Our primary focus has been the elucidation of the processes surrounding differentiation, function, and injury of mammalian airway ciliated epithelial cells and how these cells respond to challenge by infectious agents, environmental irritants including tobacco smoke, and pharmacologic agents. Our laboratory is also part of a large national center for diagnosis, research, and treatment of Primary Ciliary Dyskinesia, a genetic disease affecting mucociliary clearance of the airways. This laboratory is designed around facilitating light and electron microscopic
analyses but collaborates closely with other laboratories and colleagues working on cell and molecular biology topics in airway epithelial cell biology.
Molecular evolution and mechanistic enzymology find powerful synergy in our study of aminoacyl-tRNA synthetases, which translate the genetic code. Class I Tryptophanyl-tRNA Synthetase stores free energy as conformational strain imposed by long-range, interactions on the minimal catalytic domain (MCD) when it binds ATP. We study how this allostery works using X-ray crystallography, bioinformatics, molecular dynamics, enzyme kinetics, and thermodynamics. As coding sequences for class I and II MCDs have significant complementarity, we also pursuing their sense/antisense ancestry. Member of the Molecular & Cellular Biophysics Training Program.
Developing and applying novel mass spectrometry (MS)-based proteomics methodologies for high throughput identification, quantification, and characterization of the pathologically relevant changes in protein expression, post-translational modifications (PTMs), and protein-protein interactions. Focuses in the lab include: 1) technology development for comprehensive and quantitative proteomic analysis, 2) investigation of systems regulation in toll-like receptor-mediated pathogenesis and 3) proteomic-based mechanistic investigation of stress-induced cellular responses/effects in cancer pathogenesis.
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.
Our research is concerned with proteases and their inhibitors in various disease processes (thrombosis and cancer); our science tools are structure-activity, cell biology and signaling, pathobiology, immunohistochemistry, and in vivo models.
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.
The major interest of this laboratory is the differentiation and regulation of autoreactive B cells in health and disease. Our long-range goal is to identify and understand the mechanisms that regulate autoreactive B cells and how they fail in disease. Such information is key to devise rational new therapeutic strategies for the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE). The lab currently has three main research focuses: 1) regulation of B cells specific for the ribonucleoprotein antigen Sm, a target of the immune system in SLE, 2) analysis of how Epstein Barr virus (EBV) contributes to SLE and 3) investigation of activation of anti-Sm B cells in blood of human SLE patients.
Cross-talk between insulin like growth factor -1 and cell adhesion receptors in the regulation of cardiovascular diseases and complications associated with diabetes
The research in our laboratory involves several major projects related to the molecular pathogenesis of human cancer and investigations related to the biology of liver stem-like progenitor cells, including (i) characterization of human liver tumor suppressor genes, (ii) analysis of genetic determinants of breast cancer, (iii) investigation of mechanisms governing aberrant DNA methylation in breast cancer, (iv) liver progenitor cell responses after toxic liver injury, and (v) transplantation of liver stem-like progenitor cells for correction of genetic liver disease.
Diabetes and insulin resistance: lipid and carbohydrate metabolism; obesity: partition of energy between triacylglycerol storage and fatty acid oxidation; regulation of triacylglycerol synthesis; hepatic steatosis
We study how Cytotoxic T Lymphocytes (CTL) are activated during infection and cancer. Our long-term goal is to increase immunity in the case of infection or cancer and to decrease immunity in the case of autoimmunity. The approaches that we use include x-ray crystallography and other biophysical techniques such as SPR and ITC, and immunological assays. We are currently working on three systems. 1) basic immunology to understand how cytotoxic T cells are signaled to kill infected or cancer cells. 2) immunotherapy of melanoma using modified T cell receptors. 3) Determining why specific T cells populate pancreatic islets of Langerhans in Type I diabetes. Students working on these projects could work on immunological or biophysical aspects (or both) depending on their interests. Member of the Molecular & Cellular Biophysics Training Program.
Our lab is studying the molecular mechanisms which are involved in the induction and proliferation and patterning of cardiac progenitor cell populations. To identify the molecular pathways involved in these processes, we have used Xenopus and mouse as model systems with particular focus on the endogenous role of genes implicated in the early steps of cardiogenesis and human congenital heart disease. Present projects in the lab involve embryological manipulations, tissue explant cultures, molecular screens as well as protein-DNA interaction experiments, biochemistry and promoter analysis.
We study cell cycle control of DNA replication licensing, the process that renders replication origins competent to initiate DNA synthesis. We investigate how the replication process is linked to cell cycle progression and the signaling pathways that gather and transmit information about the cellular environment. Our experimental approach is to manipulate human cells in culture (both cancer cell lines and normal cells) through a variety of molecular and genetic strategies; some projects utilize budding yeast as a model system due to the sophisticated genetic tools available in that organism. We measure protein abundance and stability, chromatin localization and modifications, cell cycle progression, protein-protein interactions, and checkpoint functions. Our long-term goals are to understand the molecular events that ensure genome stability and how those events are disrupted in cancer cells.
The primary research area my lab is the regulation of meiotic recombination at the genomic level in higher eukaryotes. Genomic instability and disease states, including cancer, can occur if the cell fails to properly regulate recombination. We have created novel tools that give our lab an unparalleled ability to find mutants in genes that control recombination. We use a combination of genetics, bioinformatics, computational biology, cell biology and genomics in our investigations. A second research area in the lab is the role of centromere DNA in chromosome biology. We welcome undergraduates, graduate students, postdoctoral fellows and visiting scientists to join our team.
Mechanisms of DNA replication, DNA repair, and cell cycle checkpoints are studied in cultured human cells and using biochemical assays in vitro. It includes translesion synthesis by DNA polymerase eta and its role in suppressing mutagenesis by solar radiation. Inherited and acquired defects in the network of protection of genetic stability are associated with increased risk for mutations underlying cancer pathogenesis. Current goals are to identify key molecular events in melanoma development associated with sun exposure. Other collaborative studies aim at localization of functional origins and characterization of DNA replication dynamics.
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.
The main research project is to determine the role of intercellular junctions in normal development, cell aging and cataract formation in human and animal lenses.
Our lab is interested in molecular mechanisms of oncogenesis, specifically as regulated by Ras and Rho family small GTPases. We are particularly interested in understanding how membrane targeting sequences of these proteins mediate both their subcellular localization and their interactions with regulators and effectors. Both Ras and Rho proteins are targeted to membranes by characteristic combinations of basic residues and lipids that may include the fatty acid palmitate as well as farnesyl and geranylgeranyl isoprenoids. The latter are targets for anticancer drugs; we are also investigating their unexpectedly complex mechanism of action. Finally, we are also studying how these small GTPases mediate cellular responses to ionizing radiation - how do cells choose whether to arrest, die or proliferate?
Research in the lab is focused on four major areas - (1) Genetic, cellular, and genomic analyses of Drosophila CNS development, (2) Brain development and behavior, (3) Molecular genetics of gene regulatory pathways, and (4) Control of cell migration and fusion events.
Our laboratory has research interests that include developmental neurotoxicity, with an emphasis on the use of mode-of-action models to study the impact of endocrine disruptors and the cumulative risk of thyroid disruptors and pesticides.
The Cyr laboratory studies cellular mechanisms for cystic fibrosis and prion disease. We seek to determine how protein misfolding leads to the lung pathology associated with Cystic Fibrosis and the neurodegeneration associated with prion disease.
The work in our laboratory is focused on understanding the molecular pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic human virus. KSHV is associated with several types of cancer in the human population. We study the effect of KSHV viral proteins on cell proliferation, transformation, apoptosis, angiogenesis and cell signal transduction pathways. We also study viral transcription factors, viral replication, and the interactions of KSHV with the human innate immune system. Additionally, we are developing drug therapies that curb viral replication and target tumor cells.
We use the premier model plant species, Arabidopsis thaliana, and real world plant pathogens like the bacteria Pseudomonas syringae and the oomycete Hyaloperonospora parasitica to understand the molecular nature of the plant immune system, the diversity of pathogen virulence systems, and the evolutionary mechanisms that influence plant-pathogen interactions. All of our study organisms are sequenced, making the tools of genomics accessible.
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.
With a particular interest in pediatric solid tumors, our lab aims to develop a mechanistic understanding of the role of aberrant or dysregulated transcription factors in oncogenesis.
We study Borrelia burgdorferi (the agent of Lyme disease) as a model for understanding arthropod vector-borne disease transmission. We also study the epidemiology and pathogenesis of dengue viruses associated with hemorrhagic disease.
Our research centers on understanding the
molecular basis of human carcinogenesis. In particular, a major focus of our studies is the Ras oncogene and Ras-mediated signal transduction. The goals of our studies include the delineation of the complex components of Ras signaling and the development of anti-Ras inhibitors for cancer treatment. Another major focus of our studies involves our validation of the involvement of Ras-related small GTPases (e.g., Ral, Rho) in cancer. We utilize a broad spectrum of technical approaches that include cell culture and mouse models, C. elegans, protein crystallography, microarray gene expression or proteomics analyses, and clinical trial analyses.
We study how mammalian cells activate the programmed cell death pathway and die by apoptosis. We have focused our work on identifying unique mechanisms by which this pathway is regulated in postmitotic cells such as neurons, cardiomyocytes, and myotubes, as well as cancer, senescent, and stem cells. Excessive cell death is seen in many pathological conditions such as after stroke, neurodegeneration or cardiovascular diseases. In contrast, reduced cell death is a hallmark of cancers. Therefore, discovering the mechanism by which mammalian cells regulate cell death has significant therapeutic implications.
The direct fabrication and harvesting of monodisperse, shape-specific nano-biomaterials are presently being designed to reach new understandings and therapies in cancer prevention, diagnosis and treatment.
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.
1) Identification of critical elements of human genetic variability contributing to pain sensitivity and pathophysiological pain states, 2) identification of therapeutic targets for pain management, 3) studying molecular hierarchy of functional SNPs commonly present in human population and 4) studying the molecular mechanisms of gene expression regulation.
Our lab tries to understand viral pathogenesis. To do so, we work with two very different viruses - West Nile Virus (WNV) and Kaposi¹s sarcoma-associated herpesvirus (KSHV/HHV-8).
We use an integrated approach (genomics, proteomics, computational biology) to study the molecular mechanisms of hormone and drug desensitization. Our current focus is on RGS proteins (regulators of G protein signaling) and post-translational modifications including ubiquitination and phosphorylation.
The Dokholyan group focuses primarily on understanding protein dynamics, more specifically on how induced changes in protein folding and aggregation lead to diseases, such as cystic fibrosis, many types of cancers, and a number of neurodegenerative diseases. The Dokholyan group focuses on several such diseases, including Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, and Huntington disease. The Dokholyan group is developing a hierarchy of molecular models, from simplified coarse-grained models to more detailed ones, to create a novel multi-scale simulation methodology. This methodology will enable simulations of large molecular complexes at the biologically-relevant time scales, thereby allowing to directly glance into processes associated with human diseases. Member of the Molecular & Cellular Biophysics Training Program.
My lab studies membrane traffic between the trans-Golgi network and endosomal organelles. This central feature of eukaryotic cell biology is important for functions of the human body; including the ability to recognize and destroy infective agents, sugar uptake in response to insulin and the proper reaction of cells to growth factors-a feature important in normal development and that is often inappropriately regulated in cancer. We have two main types of projects in the lab; characterizing protein-protein interactions important for membrane traffic and chemical genetic approach to identify compounds that regulate membrane traffic.
Mechanisms of cell cycle control by cyclin dependent kinases (CDK's) and gene expression during Drosophila development, including how transcription factors (the pRB tumor suppressor and E2F), RNA metabolism (histone pre-mRNA processing), and protein ubiquitination and proteolysis (cullin dependent ubiquitin ligases) regulate the G1-S transition and DNA replication.
The study of opioid analgesics, with particular focus on opioids that are less likely to produce physical dependence and abuse. Research in the laboratory has examined the relationship between the analgesic effects of opioid analgesics and their interaction with specific opioid receptor types. A more recent research interest includes investigations of genetically-altered mice with relevance to drug dependence and the development of models of mouse behavior for examining behavioral phenotypes related to a range of behavioral disorders.
Our lab is interested in how signals from membrane receptors are transduced to the nucleus altering gene expression, cell shape, proliferation and differentiation. We are particularly interested in tyrosine-specific protein kinases in breast and prostate cancer, as well as lymphoma/leukemia. Particular focus of the lab include:1) roles of the EGF receptor family and related molecules HER4/ErbB4 in growth inhibition and differentiation and 2) Mer (a novel receptor tyrosine kinase) and how signals downstream from Mer enhance prostate tumorigenesis.
The Elston lab is interested in understanding the dynamics of complex biological systems, and developing reliable mathematical models that capture the essential components of these systems. The projects in the lab encompass a wide variety of biological phenomena including signaling through MAPK pathways, noise in gene regulatory networks, airway surface volume regulation, and understanding energy transduction in motor proteins. A major focus of our research is understanding the role of molecular level noise in cellular and molecular processes. We have developed the software tool BioNetS to accurately and efficiently simulate stochastic models of biochemical networks
We are characterizing the structural signals that are responsible for moving proteases normally stored intracellularly in lysosomes into the extracellular environment, where they may participate in tumor cell metastasis. One putative mediator of this altered protease targeting is an endosomal integral membrane protein that behaves like a cellular "dirty bomb", undergoing proteolysis which releases fragments that target to various cellular sites where they serve distinct functions. The multiple proteolytic cleavages ultimately release the cytoplasmic tail from the membrane. This tail, which possesses a putative signal for import into the nucleus, can modify other proteins with ubiquitin, which causes them to be degraded rapidly. Proteolysis of the putative receptor is mediated by the same enzymes that cleave the Alzheimer's precursor protein into fragments that can aggregate to form plaques in the brain. When neurite outgrowth is stimulated, expression of this protein is upregulated, suggesting that it also plays a role in development. We are using biochemical characterization of the protein's domain structure to relate its proteolysis, cellular targeting, and signaling to the nucleus to altered targeting of lysosomal enzymes.
The research in my lab is divided into two main areas - 1) Atomic force microscopy and fluorescence studies of protein-protein and protein-nucleic acid interactions, and 2) Mechanistic studies of transcription elongation. My research spans the biochemical, biophysical, and analytical regimes.
Investigation of genes/proteins that play key roles during embryonic and postnatal development of craniofacial/oral/dental structures; and their contribution to normal variation and to congenital and acquired disorders.
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.
Genetic instability in cultured human cells and yeast, microsatellite mutations, DNA mismatch repair, hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome), human genetics, somatic-cell genetics.
Involvement of the epidermal growth factor receptor and its ligands in development, differentiation, and carcinogenesis of the mammary gland. Signaling mechanisms of endocrine disrupting toxicants having adverse effects on mammary gland development and the ability of the gland to lactate. Mechanism of action of atrazine, simazine, and cyanazine in the brain.
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.
The central goal of my research is to understand how immune cells are activated and regulated within the Central Nervous System. Our research looks at the different pathways of activation of the microglia, the role of the microglia in sensory responses, and the role of stress responses in activating and regulating the response of the microglia. We are currently investigating the mechanism of microglia activation and regulation in Parkinson's Disease (PD). We also study the mechanisms by which CD8 T lymphocytes dictate the nature of inflammatory responses to cancer cells. Research in my laboratory seeks to delineate the immunologic mechanisms involved in the generation of protective anti-tumor responses in CD8 cell populations, and in developing therapies for treatment of cancer.
Research interests include: transport processes in the lung, flow and structure of nano-materials & macromolecular fluids, weakly compressible transport phenomena, solitons and optical fiber applications, inverse problems for material characterization and modeling of transport in multiphase porous media.
Our work is focused on understanding how major histocompatibility complex (MHC) molecules function in the immune response to pathogens. This simple question involves the most fundamental aspect of immunology - self/non-self discrimination.
The role of associative learning and memory in cue-induced relapse to drug seeking and the role of the prefrontal cortex in suppression of drug seeking. Studies in my laboratory utilize surgical, behavioral, and histological techniques as well as neuropharmacological manipulations.
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 uncovering the fundamental systems-wide processes and mechanisms that underlie life, with a human-health focus. We apply a combination of both modern and traditional tools to this pursuit, including bioinformatics, proteomics, microarrays, molecular genetics, bench work, and software development. Current research areas we focus on include: 1) locating the molecular mechanisms that underlie antibiotic tolerance in the bacteria Pseudomonas aeruginosa, to address the threat that drug resistant organisms pose to those with COPD and Cystic Fibrosis; 2) annotation of the human genome with proteomic data, to determine which genes are translated and when, and how those correlate with prevalent diseases such as cancer; 3) development of computational agent-based models of intramolecular pathways and pathogen-host interactions in HIV, to determine how host-pathogen interactions relate to disease progression; 4) development of software tools for analysis of RNA structures, such as the viral HIV genome, to assist with determining how RNA structure impacts function; and 5) developing software for finding post-translational modifications (PTMs) on proteins by integrating proteomic data sets, to determine the role that these play on cellular signaling in healthy and diseased states. We have a wide diversity lab members, from microbiology bench scientists to computer scientists, and would be a great fit for a student looking for a broad, cross-disciplinary training environment focused on either microbiology and/or genomics.
Dr. Gilmore’s research group is applying state-of–the-art magnetic resonance imaging and image analysis techniques to study human brain development in 0-6 year olds, with a focus on cortical gray and white matter development. Studies include normally developing children, twins, and children at high risk for schizophrenia and bipolar illness. We are beginning to study the contributions of specific genes of risk to brain development in humans. A collaborative study with the Harlow Primate Lab at the University of Wisconsin is using imaging to study brain development in Rhesus monkeys, and the impact of prenatal exposure to maternal infection on brain development.
Successful respiratory pathogens must be able to respond swiftly to a wide array of sophisticated defense mechanisms in the mammalian lung. In histoplasmosis, macrophages -- a first line of defense in the lower respiratory tract -- are effectively parasitized by Histoplasma capsulatum. We are studying this process by focusing on virulence factors produced as this "dimorphic" fungus undergoes a temperature-triggered conversion from a saprophytic mold form to a parasitic yeast form. Yersinia pestis also displays two temperature-regulated lifestyles, depending on whether it is colonizing a flea or mammalian host. Inhalation by humans leads to a rapid and overwhelming disease, and we are trying to understand the development of pneumonic plague by studying genes that are activated during the stages of pulmonary colonization. [note: Dr. Goldman will be moving to UNC in Summer 2008]
We are using C. elegans embryos to address fundamental issues such as how cells move to specific positions during embryonic morphogenesis, how the orientation of cell division is determined, how the mitotic spindle is positioned in cells and how cells respond to cell signaling. We use diverse methods, including methods of cell biology, developmental biology, forward and reverse genetics including RNA interference, biochemistry, molecular biology and live microscopy of cells and the cytoskeleton. We are also developing water bears as a
new model system to study the evolution of development.
Our primary research is in the area of computational systems biology, with particular interest in the study of biological signaling networks; trying to understand their structure, evolution and dynamics. In collaboration with wet lab experimentalists, we develop and apply computational models, including probabilistic graphical and multivariate methods along with more traditional engineering approaches such as system identification and control theory, to current challenges in molecular biology and medicine. Examples of recent research projects include: prediction of protein interaction networks, multivariate modeling of signal transduction networks, and development of methods for integrating large-scale genomic data sets.
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 research goal is to understand how bacterial pathogens cause disease on their hosts. We are working with a plant pathogen, Pseudomonas syringae which introduces virulence proteins into host cells to suppress immune responses. Our laboratory collaborates with Jeff Dangl's lab in the UNC Biology Department using genomics approaches to identify P. syringae virulence proteins and to discover how they alter plant cell biology to evade the plant immune system and cause disease.
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.
We are interested in basic DNA-protein interactions as related to - DNA replication, DNA repair and telomere function. We utilize a combination of state of the art molecular and biochemical methods together with high resolution electron microscopes.
The primary thrust of research in this lab seeks to understand the effects of neurosteroids on development, particularly how neurosteroid levels in the developing cortex affect patterns of migration and neurogenesis in the prefrontal cortex. A secondary interest is the mechanisms by which increases in neurosteroid levels might be relevant to their therapeutic action.
Dr. Gulley's research is on Epstein-Barr virus (EBV)-related malignancies. Molecular and immunohistochemical techniques are used to characterize infected tissues. We validate new assays to help diagnose and monitor affected patients.
The Gupta group uses statistical and computational approaches to find conserved stochastic patterns or motifs in genome sequences. They are particularly interested in using these approaches to discover gene regulatory modules and interaction networks involved in specific biological processes.
Dynamic control of signaling networks in living cells; Rho family and MAPK networks in motility and network plasticity; new tools to study protein activity in living cells (i.e., biosensors, protein photomanipulation, microscopy). Member of the Molecular & Cellular Biophysics Training Program and the Medicinal Chemistry Program.
My lab studies a gene silencing phenomenon called RNA interference, or RNAi. We are interested in the role of RNAi in regulating endogenous genes, particularly those involved in cancer progression pathways.
We focus on mechanistic/structural aspects of regulatory proteins (heterotrimeric and Ras family GTPases, RGS proteins, and PLC isozymes) involved in inositol lipid signaling, and on G protein-coupled receptors for extracellular nucleotides.
The Neurotoxicology Group examines the role of microglia interactions with neurons and the associated immune-mediated responses in brain development and aging as they relate to the initiation of brain damage, the progression of cell death, and subsequent repair/regenerative capabilities. We have an interest in the neuroimmune response with regards to neurodegenerative diseases such as, Alzheimer's disease.
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
We study alphavirus infection to model virus-induced disease. Projects include 1) mapping viral determinants involved in encephalitis, and 2) using a mouse model of virus-induced arthritis to identify viral and host factors associated with disease.
bioinformatics, scholarly communications, digital libraries, user interface design, annotation, virtual environments, medical informatics, databases and datamining.
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.
