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[ PhD Program: Biochemistry Keyword: ]

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NameEmailPhd ProgramResearch InterestsPublications
Allbritton, Nancy email , , , , publications

The overall focus of the laboratory is to quantitatively measure the activity of proteins in cellular signaling networks to understand the relationships of these intracellular pathways in regulating cell health and disease. These networks are composed of interacting proteins and small molecules that work together in a concerted manner to regulate the cell in response to its environment. Despite the importance of these key signaling molecules in controlling the behavior of cells, most of these proteins and metabolites can not be quantified in single cells. There is a need throughout biology for new technologies to identify and understand the molecular circuits within single cells. A research goal is to develop new methods that will broaden the range of measurements possible at the single-cell level and then to utilize these methods to address fundamental biologic questions. We are pursuing this task by bringing to bear diverse techniques from chemistry, physics, biology and engineering to develop new analytical tools to track signal transduction within individual cells. Our research is a multidisciplinary program for the development and application of new analytical methods with two main focus areas: 1) techniques to monitor cellular signaling, and 2) microfabricated cellular analysis systems.

Bear, James E. email , , , , , , , publications

Our lab uses a combination of genetics, high-resolution cellular and animal imaging, animal tumor models and microfluidic approaches to study the problems of cell motility and cytoskeletal organization. We are particularly interested in 1) How cells sense cues in their environment and respond with directed migration, 2) How the actin cytoskeleton is organized at the leading edge of migrating cells and 3) How these processes contribute to tumor metastasis.

Bergmeier, Wolfgang email , , , , , publications

Our research focuses on the adhesion mechanisms of platelets and neutrophils to sites of vascular injury/ activation. For successful adhesion, both cell types rely on activation-dependent receptors (integrins) expressed on the cell surface. We are particularly interested in the role of calcium (Ca2+) as a signaling molecule that regulates the inside-out activation of integrin receptors. Our studies combine molecular and biochemical approaches with microfluidics and state-of-the-art in vivo imaging (intravital microscopy) techniques.

Bourret, Bob email , , , , publications

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 identify and understand the features that control the rates of several different types of protein phosphorylation and dephosphorylation reactions.  The kinetics of phosphotransfer reactions can vary dramatically 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.

Bowers, Albert A email , , , , publications

Research in the Bowers lab focuses on investigation of structure activity relationships and mechanisms of action of natural product-derived small molecule therapeutics.  We employ a variety of methods to build and modify compounds of interest, including manipulation of natural product biosynthesis, chemical synthesis, and semi-synthesis.  One major area of research in the lab is the rationale engineering of biosynthetic pathways to make bacterial drug factories.  Compounds targeting transcriptional regulation of cancer as well as multi-drug resistant venereal infections are currently under investigation in the lab.

Brustad, Eric M email , , , publications

The Brustad group is interested in applying chemical principles to expand biological systems beyond Nature’s design. We make use of developing technologies such as unnatural amino acid mutagenesis and non-natural cofactor design to increase the chemical functionality available to proteins. Current efforts are directed towards the genetic incorporation of organocofactor mimics as well as heme protein engineering through the incorporation of orthogonal metalloporphyrin scaffolds. We combine methods in synthetic chemistry, molecular biology, X-ray crystallography, and directed evolution to optimize the function of our protein engineering efforts.

Burks, Wesley email , , , , publications

The UNC Food Allergy Institute (UNCFAI) was established in 2012 to address the growing needs of children and adults with food allergy. Program investigators study the biologic basis of food allergy in the laboratory and in clinical research studies seeking to better understand the role of allergen-specific IgE and the mechanism of allergen immunotherapy. The Institute provides comprehensive, family-centered patient care for food allergy, food-related anaphylaxis, and other related disorders like atopic dermatitis and eosinophilic esophagitis.

Campbell, Sharon email , , , , publications

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.

Carter, Charles email , , , , , , publications

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.

Church, Frank C. email , , , , , , publications

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.

Cohen, Todd email , , , , publications

My research aims to uncover the molecular aspects of protein aggregation diseases (also called PAD) which include neurodegenerative diseases (such as Alzheimer’s disease and Amyotrophic Lateral Sclerosis), myofibrillar myopathies (such as muscular dystrophies), as well as the formation of age-related cataracts.  Although very distinct, these disorders share a common underlying pathogenic mechanism.  Using a combination of biochemistry and in vitro approaches, cell biology, and primary cells / transgenic mouse models, we will investigate the post-translational modifications (PTMs) that drive these disease processes. Ultimately, this research will provide a platform for future drug discovery efforts against these devastating diseases.

Conlon, Frank email , , , , , , publications

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.

Cook, Jeanette (Jean) email , , , , , , , publications

The Cook lab studies the major transitions in the cell division cycle and how perturbations in cell cycle control affect genome stability. We have particular interest in mechanisms that control protein abundance and localization at transitions into and out of S phase (DNA replication phase) and into an out of quiescence. We use a variety of molecular biology, cell biology, biochemical, and genetic techniques to manipulate and evaluate human cells as they proliferate or exit the cell cycle. We collaborate with colleagues interested in the interface of cell cycle control with developmental biology, signal transduction, DNA damage responses, and oncogenesis.

Cotter, Peggy email , , , , publications

Dr. Cotter’s research is aimed at understanding molecular mechanisms of bacterial pathogenesis. Using Bordetella species as models, her group is studying the role of virulence gene regulation in respiratory pathogenesis, how virulence factors activate and suppress inflammation in the respiratory tract, and how proteins of the Two Partner Secretion pathway family are secreted to the bacterial surface and into the extracellular environment. A second major project is focused on Burkholderia pseudomallei, an emerging infectious disease and potential biothreat agent. This research is aimed at understanding the role of autotransporter proteins in the ability of this organism to cause disease via the respiratory route.

Cyr, Douglas M. email , , , , publications

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.

Dohlman, Henrik email , , , , , , publications

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.

Duncan, Alex email , , , , publications

My lab studies a recently identified pathogen-sensing signaling complex known as the inflammasome. The inflammasome is responsible for the proteolytic maturation of some cytokines and induces a novel necrotic cell death program. We have found that critical virulence factors from certain pathogens are able to activate NLRP3-mediated signaling, suggesting these pathogens may exploit this host signaling system in order to promote infections.  Our lab has active research projects in several areas relating to inflammasome signaling ranging from understanding basic molecular mechanisms of the pathway to studying the role of the system in animal models of infectious diseases.

Earp, H. Shelton email , , , publications

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 the roles of :1) the EGF receptor family and related molecules e.g. HER4/ErbB4 in growth inhibition and differentiation, 2) the intracellular tyrosine kinase Ack which tyrosine phosphorylates the androgen receptor in androgen-independent prostate cancer and 3) a receptor tyrosine kinase that we cloned, Mer, that is expressed ectopically in childhood leukemias conferring a chemoresistant signal.  Mer also function in tumor-associated macrophages in a manner that appears to enhance tumor growth and immune system evasion.

Emanuele, Michael email , , , , , publications

Our lab applies cutting edge genetic and proteomic technologies to unravel dynamic signaling networks involved in cell proliferation, genome stability and cancer. These powerful technologies are used to systematically interrogate the ubiquitin proteasome system (UPS), and allow us to gain a systems level understanding of the cell at unparalleled depth. We are focused on UPS signaling in cell cycle progression and genome stability, since these pathways are universally perturbed in cancer.

Erie, Dorothy email , , , , publications

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.

Errede, Beverly email , , , publications

Yeast molecular genetics; MAP-Kinease activation pathways; regulation of cell differentiation.

Goldman, William email , , , , publications

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.

Graves, Lee M. email , , , , publications

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.

Griffith, Jack email , , , , , , publications

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.

Gupton, Stephanie email , , , , , , , publications

During cell shape change and motility, a dynamic cytoskeleton produces the force to initiate plasma membrane protrusion, while vesicle trafficking supplies phospholipids and membrane proteins to the expanding plasma membrane. Extracellular cues activate intracellular signaling pathways to elicit specific cell shape changes and motility responses through coordinated cytoskeletal dynamics and vesicle trafficking. In my lab we are investigating the role of two ubiquitin ligases, TRIM9 and TRIM67, in the cell shape changes that occur during neuronal development. We utilize a variety techniques including high resolution live cell microscopy, gene disruption, mouse models, and biochemistry to understand the complex coordination of cytoskeletal dynamics and membrane trafficking driving neuronal shape change and growth cone motility in primary neurons.

Hahn, Klaus email , , , , , , , , , publications

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.

Hammond, Scott email , , , , , publications

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.

Harden, Kendall email , , , , , publications

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.

Hicks, Leslie M. email , , , , publications

Research in the Hicks lab focuses on development and implementation of mass spectrometric approaches for protein characterization including post-translational modifications, as well as the identification of bioactive peptides/proteins from plants. Keywords: proteins / peptides, proteomics, PTM, enzymes, analytical chemistry, mass spectrometry, separations / chromatography, plants, algae

Hursting, Stephen D email , , , , publications

Dr. Hursting’s lab focuses on the molecular and metabolic mechanisms underlying nutrition and  cancer associations, particularly the impact of obesity and energy balance modulation (eg, calorie restriction, exercise) on cancer development or responses to chemotherapy. Primarily using genetically engineered mouse models of pancreatic, colon and breast cancer, Dr. Hursting has identified the IGF-1/Akt/mTOR and NF-kB signaling pathways as key targets for breaking the obesity- cancer link.  He has also established in several preclinical models of pancreatic and breast cancer that obesity impacts the response to various forms of chemotherapy.  In addition, the Hursting lab is involved in several translational research collaborations linking mouse model studies with clinical trials, and his group has expertise in measuring metabolic hormones, growth factors, inflammatory cytokines and chemokines in serum and tissue from rodents and humans.

Jacobson, Ken email , , , publications

Structure, dynamics and function of viral domains in biomembranes.  Photomanipulation and traction mapping applied to the migration of single cells. Investigation of the mechanochemical basis of cell oscillations using systems biology approaches coupled with experiments.

James, Lindsey Ingerman email , , publications

We are interested in modulating the activity of chromatin reader proteins with small-molecule ligands, specifically potent and selective chemical probes, in order to open new avenues of research in the field of epigenetics. Our work has pioneered the biochemical assays and medicinal chemistry strategies for high quality probe development for methyl-lysine (Kme) reader proteins, as well as the means by which to evaluate probe selectivity, mechanism of action, and cellular activity. Using a variety of approaches, we utilize such chemical tools to improve our understanding of their molecular targets and the broader biological consequences of modulating these targets in cells. We are also interested in developing novel methods and screening platforms to discover hit compounds to accelerate Kme reader probe discovery, such as affinity-based combinatorial strategies, as well as innovative techniques utilizing our developed antagonists to more fully understand the dynamic nature of chromatin regulation.

Jarstfer, Michael email , , , , publications

The Jarstfer lab uses an interdisciplinary approach to solve biological problems that are germane to human health.   Currently we are investigating the structure of the enzyme telomerase, we are developing small-molecules that target the telomere for drug discovery and chemical biology purposes, and we are investigating the signals that communicate the telomere state to the cell in order to control cellular immortality. We are also engaged in a drug/chemical tool discovery project to identify small molecules that control complex social behavior in mammals.  Techniques include standard molecular biology and biochemistry of DNA, RNA, and proteins, occasional organic synthesis, and high throughput screening.

Johnson, Gary L. email , , , , publications

Spatio-temporal regulation of signal relay systems in cells using live cell fluorescence imaging and targeted gene disruption of signaling proteins to define their role in development, physiology and pathophysiology.

Jones, Alan email , , , , , , , publications

The Jones lab is interested in heterotrimeric G protein-coupled signaling and uses genetic model systems to dissect signaling networks.  The G-protein complex serves as the nexus between cell surface receptors and various downstream enzymes that ultimately alter cell behavior. Metazoans have a hopelessly complex repertoire of G-protein complexes and cell surface receptors so we turned to the reference plant, Arabidopsis thaliana, and the yeast, Saccharomyces cerevisiae, as our models because these two organisms have only two potential G protein complexes and few cell surface receptors.  Their simplicity and the ability to genetically manipulate genes in these organisms make them powerful tools.  We use a variety of cell biology approaches, sophisticated imaging techniques, 3-D protein structure analyses, forward and reverse genetic approaches, and biochemistries.

Ke, Hengming email , , , , publications

Our research focuses on the structure and function of medically important proteins from the crystallographic approach.  The current topics include cycolphilin, calcineurin, heat shock protein 90 (hsp90), and cyclic nucleotide phosphodiesterase.

Kesimer, Mehmet email , , , , publications

The upper airways serve to clean inspired air from physical, chemical and pathological detritus that might damage the delicate peripheral airways where oxygen exchange is achieved. It is the heart of a powerful two tiered  innate immune system based upon a  layer of mucus that captures the incoming material that is moved over a bed of cilia. The system is called the muco-ciliary escalator.
Failure of this complex protective system is associated with a wide variety of diseases such as cancer and chronic inflammatory diseases. Biomolecules in mucus are split into two distinct groups, the first group being of globular type proteins between 6 kDa to 200 kDa and the second being of mucins which are large, space-filling glycoconjugates of 200 kDa to 100 MDa, with most of this mass being of carbohydrate in origin. Besides these biomolecules, mucus also contains secreted vesicles (exosomes) with innate immune properties. In chronic inflammatory lung diseases like cystic fibrosis (CF), chronic bronchitis (COPD) and asthma, mucus quantity and quality is altered and it is not efficiently removed from the lungs, causing airway obstruction, impaired gas exchange, bacterial colonization & infection and damage to lung tissue. The long term goal of our laboratory is to understand how this innate immune barrier is dynamically organized around the protective macromolecules under normal and pathological conditions. Currently, research in the Kesimer laboratory is focused on three main fundamentally important areas: 1- How mucins and globular proteins are organized within the airway mucosal barrier and how they are altered in disease pathogenesis, 2- How mucins are processed to mature after granular release for optimal function and how this progression is altered in chronic lung diseases, CF in particular, and 3- The role of extracellular vesicles in the airway mucosal barrier. Our laboratory is established with a wide range of state of the art biochemical, biophysical and proteomics methods including UPLC-Orbitrap mass spectrometry, atomic force microscopy, dynamic and static light scattering, and a variety of surface biophysics tools including QCM-D.

Krupenko, Natalia email , , , , , publications

My laboratory is interested in the role of folate and related metabolic pathways in methyl group metabolism, and their involvement in pathogenesis and etiology of diseases. We have recently discovered a novel function of a folate-binding methyltransferase GNMT in the regulation of cellular proliferation, and now study the genetic variations in GNMT and their effects on new function. Our lab is also interested in the cross talk between folate metabolism and sphingolipid pathways as a mediator of folate stress with the goal of exploiting this connection to improve human health.

Krupenko, Sergey email , , , , publications

Dr. Krupenko’s research is focused on the role of folate metabolism in cellular homeostasis and cancer disease. He is especially interested in the function of a major folate enzyme and a putative tumor suppressor ALDH1L1 as metabolic regulator and a guardian of non-malignant phenotype. At present he studies function of this enzyme and related proteins using mouse knockout models. Recently his research team has also demonstrated that dietary folate regulates cancer metastasis. He now pursues studies of specific signaling pathways involved in metastatic response to dietary folate status.

LeCluyse, Edward L email , , , , publications

Dr. Edward (Ed) LeCluyse is currently a Senior Research Investigator in the Institute for Chemical Safety Sciences at The Hamner Institutes of Health Sciences.  Dr. LeCluyse leads a program initiative to identify and develop novel in vitro hepatic model systems to examine cellular responses to drugs and environmental chemicals that target known toxicity pathways. The focus of his research efforts has been to create more organotypic, physiologically-relevant in vitro models that integrate the architectural, cellular and hemodynamic complexities of the liver in vivo.

Lee, Andrew email , , , , publications

We study protein structure and dynamics as they relate to protein function and energetics. We are currently using NMR spectroscopy (e.g. spin relaxation), computation, and a variety of other biophysical techniques to gain a deeper understanding of proteins at atomic level resolution.  Of specific interest is the general phenomenon of long-range communication within protein structures, such as observed in allostery and conformational change.  A. Lee is a member of the Molecular & Cellular Biophysics Training Program.

Li, Bo email , , , , publications

Our research focuses on the discovery and design of new gene-encoded bioactive small molecules from bacteria.  We are interested in understanding enzymes involved in their biosynthesis, their therapeutic mechanisms of action, and implications in health and diseases, in particular with respect to the human microbiome.  This work is driven by intensive development of new metabolomics and genomics technologies.  We subsequently manipulate and engineer these biosynthetic pathways to make new and improved molecules as potential therapeutics such as antibiotics.

Liu, Jian email , , , publications

The overall goal of our research is to develop an enzyme-based approach to synthesize heparin- and heparan sulfate-like therapeutics.  The lab is currently focusing on improving the anticoagulant efficacy of heparin drug as well as synthesizing heparin-like compounds that inhibit herpes simplex virus infections.  We are also interested in using protein and metabolic engineering approaches for preparing polysaccharides with unique biological functions.

Liu, Pengda email , , , , publications

If you are interested in developing new biochemical/molecular techniques/tools to advance our understanding of biology, and if you are interested in signal transduction pathway analyses and identification of cancer biomarkers, our research group may help you to achieve your goals, as we have the same dreams. We are especially interested in deciphering the molecular mechanisms underlying aberrant signaling events that contribute to tumorigenesis, mediated through protein modifications and protein-protein interactions. Understanding these events may lead to identification of novel drug targets and provide new treatment strategies to combat human cancer.


Liu, Rihe email , , , , publications

The research interests of the Liu Lab are in functional proteomics and biopharmaceuticals. Currently we are working on the following projects:  (1). Using systems biology approaches to decipher the signaling pathways mediated by disease-related proteases such as caspases and granzymes and by post-translationally modified histones. We address these problems by performing functional protein selections using mRNA-displayed proteome libraries from human, mouse, Drosophila, and C. elegans. (2). Developing novel protein therapeutics and nucleic acid therapeutics that can be used in tumor diagnosis, treatment, and nanomedicine. We use various amplification-based molecular evolution approaches such as mRNA-display and in vivo SELEX to develop novel single domain antibody mimics on the basis of very stable protein domains or to generate aptamers on the basis of nuclease-resistant nucleic acids, that bind to important biomarkers on the surface of cancer cells. We further conjugate these biomarker-binding affinity reagents to small molecule drugs or nanoparticles for targeted delivery of therapeutic agents. (3). Identifying the protein targets of drugs or drug candidates whose action mechanisms are unknown. We combine molecular proteomic and chemical biology approaches to identify the protein targets of drugs whose target-binding affinities are modest.

Liu, Zhi email , , , , publications

Biochemistry, cell biology, and immunology of skin, immunopathogenesis of autoimmune and inflammatory skin blistering diseases.

Lockett, Matthew Ryen email , , , publications

Research in the Lockett group focuses on the development of analytical model systems to: i) chemically modify the surface of thin films, and study chemical and biochemical reactions occurring on those surfaces; ii) study drug metabolism in an environment that closely mimics the human liver; iii) measure tumor invasion in an environment that closely mimics human tissue. /  / While these problems require techniques found in analytical chemistry, biochemistry, molecular biology, bioengineering, and surface science we are particularly interested in the technologies that allow us to quantitatively measure reactions and analytes.

Maddox, Amy Shaub email , , , , , , , publications

My research philosophy is summed up by a quote from Nobelist Albert Szent-Gyorgyi: “Discovery is to see what everybody has seen and to think what nobody has thought.” My lab studies the molecular and physical mechanisms of cell shape change during cytokinesis and tissue biogenesis during development. Specifically, we are defining how cells ensure proper alignment and sliding of cytoskeletal filaments, and determining the shape of the cell throughout division. To do so, we combine developmental biology, cell biology, biochemistry, and quantitative image analysis.

Major, Michael Ben email , , , , , , publications

The overall goal of my lab is to understand how alterations in signal transduction pathways contribute to human cancer.  To that end, a systems level approach is employed wherein functional genomics, mass spectrometry-based proteomics, gene expression and mutation data are integrated.  The resulting cancer-annotated physical/functional map of a signal transduction pathway provides us with a powerful tool for mechanistic discovery in cancer biology.  We are currently working in lymphoma and lung cancer models, with a focus on the Wnt/b-catenin and Keap1/Nrf2 pathways.

Makowski, Liza email , , , , , , publications

The Makowski lab focuses on substrate metabolism or “immunometabolism” in immune cells such as macrophages and metabolic reprogramming in complex diseases such as obesity, insulin resistance, atherosclerosis, and cancer. We use mouse models, cell culture, and metabolomics to study the interaction between inflammation and nutrient sensitive pathways. Projects in lab are funded by NIH, AHA, and the Mary Kay Foundation.  Core Techniques include:  Glucose, fatty acid, cholesterol trafficking and metabolism using radiotracer biochemical studies. Cellular bioenergetics. Digital Immunohistochemical Analysis

Marchetti, Adrian email , , , , publications

We are a biological oceanography lab that performs inquiry-based science by combining physiological and molecular approaches in laboratory isolates and natural communities to investigate how marine microorganisms are affected by their environment and in turn, influence ocean biogeochemistry and ecosystem dynamics. Particular interests include studying trace metals, such as iron, that are essential for the nutrition of phytoplankton and predicting the effects of future climate changes on phytoplankton distribution and abundance.  We implement the use of environmental genomic approaches (e.g. RNA-seq) to ascertain the ways in which marine microbes have adapted and acclimate to varying environmental conditions.

Marzluff, William email , , , , , , , , , publications

We are interested in the mechanisms by which histone protein synthesis is coupled to DNA replication, both in mammalian cell cycle and during early embryogenesis in Drosophila, Xenopus and sea urchins.

Matson, Steven email , , , , publications

Research in our laboratory is focused on the enzymatic mechanisms and biological roles of DNA helicases which convert duplex DNA to ssDNA for use as a template in DNA replication and repair or as a substrate in recombination.  Defects in genes encoding DNA helicases have been linked to genomic instability leading to a variety of progeriod disorders and human cancers. Our long-range goal is to understand the mechanism of action of helicases and to define their roles in DNA metabolism. The lab also has an interest in the process of DNA transfer by bacterial conjugation – the unidirectional and horizontal transmission of genetic information from one cell to another. Conjugative DNA transfer plays a role in increasing genetic diversity in addition to propagating the spread of antibiotic resistance and microbial virulence factors. Our long-range goal is to define the function and regulation of the relaxosome, and each protein in this nucleoprotein complex, in conjugative DNA transfer.

McGinty, Robert email , , , , , publications

The McGinty lab uses structural biology, protein chemistry, biochemistry, and proteomics to study epigenetic signaling through chromatin in health and disease.  Chromatin displays an extraordinary diversity of chemical modifications that choreograph gene expression, DNA replication, and DNA repair – misregeulation of which leads to human diseases, especially cancer. We prepare designer chromatin containing specific combinations of histone post-translational modifications. When paired with X-ray crystallography and cryo-electron microscopy, this allows us to interrogate mechanisms underlying epigenetic signaling at atomic resolution.

Meissner, Gerhard email , , , , publications

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.

Nagarajan, Uma M email , , , , , publications

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen that causes Fallopian tube inflammation and subsequent tubal infertility in women.  Our current research interest is to investigate the role of an innate immune responses to chlamydial infection and its role in genital tract pathology in a mouse model of genital infection.  Specifically, we are interested in delineating pathogen recognition by the host, signaling pathways that lead to the induction of innate immune cytokines in vitro and their downstream cellular effects in vivo.  We are specifically interested in understanding the contribution type I IFN, IL-1 activation, caspases and damage associated molecular patterns in pathogenesis. The identification of host molecules involved in amplification of the inflammatory response during infection, would serve as biomarkers and therapeutic targets to prevent reproductive sequelae in women infected with Chlamydia.

Neher, Saskia email , , , , , publications

Our lab seeks to better understand the maturation and regulation of a group of human lipases.  We aim to uncover how these lipases properly fold and exit the ER, and how their activity is subsequently regulated.  We study the membrane-bound and secreted proteins that play a role in lipase regulation.  Our research can potentially impact human health as biochemical deficiencies in lipase activity can cause hypertriglyceridemia and associated disorders, such as diabetes and atherosclerosis.  We are an interdisciplinary lab and aim to address these questions using a variety of techniques, including membrane protein biochemistry, enzymology, and structural and molecular biology.

Nicholas, Robert A. email , , , , , , publications

My laboratory has two main interests: 1) Regulation of P2Y receptor signaling and trafficking in epithelial cells and platelets. Our laboratory investigates the cellular and molecular mechanisms by which P2Y receptors are differentially targeted to distinct membrane surfaces of polarized epithelial cells and the regulation of P2Y receptor signaling during ADP-promoted platelet aggregation. 2) Antibiotic resistance mechanisms. We investigate the mechanisms of antibiotic resistance in the pathogenic bacterium, Neisseria gonorrhoeae. Our laboratory investigates how acquisition of mutant alleles of existing genes confers resistance to penicillin and cephalosporins. We also study the biosynthesis of the gonococcal Type IV pilus and its contribution to antibiotic resistance.

Parise, Leslie email , , , , , , , , publications

The overall goal of our laboratory is to understand the molecular interface between cell signaling and adhesion receptors in blood diseases and cancer in order to develop novel therapeutic targets and approaches. One area of study is platelets because they become activated by cellular signals and adhere to each other and the blood vessel wall via specific adhesion receptors. These events can block blood flow, causing heart attacks and stroke, the leading causes of death in the US. Another area of research is sickle cell disease, since red blood cells in these patients are abnormally adhesive and also cause blood vessel blockages. A third area is cancer since cancer cells use similar cellular signals and adhesion receptors in tumorigenesis and metastasis. Our work involves a wide array  of technologies that include molecular, structural and cellular approaches as well as clinical/translational studies with human patients.

Pearce, Ken email , , , , , publications

We are a comprehensive, collaborative group with a primary focus on lead and early drug discovery for oncology and epigenetic targets and pathways.  Our research applies reagent production, primary assay development, high-throughput screening, biophysics, and exploratory cell biology to enable small molecule drug discovery programs in solid partnership with collaborators, both within the Center for Integrative Chemical Biology and Drug Discovery and across the UNC campus.  We apply small molecule hit discovery to highly validated biochemical targets as well as phenotypic cell-based assays.  Our methods include various fluorescence-based readouts and high content microscopy.  Examples of some of our collaborative small molecule discovery programs include, inhibition of chromatin methyl-lysine reader proteins, hit discovery for small GTPases such as K-Ras and Gaq, inhibitors of inositol phosphate kinases, inhibitors of protein-protein interactions involving CIB1 and MAGE proteins, and several cell-based efforts including a screen for compounds that enhance c-Myc degradation in pancreatic cancer cells.  In addition, we are developing a DNA-encoded library approach for hit discovery to complement traditional high-throughput screening.  Our ultimate goal is discovery of new chemical probes and medicines for exploratory biology and unmet medical needs, respectively.

Pielak, Gary J. email , , , , , publications

My graduate students and I use the formalism of equilibrium thermodynamics and the tools of molecular biology and biophysics to understand how nature designs proteins.

Ramsden, Dale email , , , , , publications

The end joining pathway is a major means for repairing chromosome breaks in vertebrates.  My lab is using cellular and cell-free models to learn how end joining works, and what happens when it doesn’t.

Redinbo, Matt email , , , , , , , publications

The Redinbo Laboratory examines dynamic cellular processes using structural, chemical, molecular and cell biology. Our goals are to discover new drugs and to elucidate molecular pathways essential to human disease.  Current projects include developing the first drugs that target the human microbiome, unraveling the nature of innate immunity in the human lung, and discovering how microbial systems exchange genes, including those that encode antibiotic resistance.

Rubenstein, David email , , , , publications

The work in my lab is focused on the regulation of cell adhesion and the inter-relationship between alterations in adhesion and the biology of the cell. Our lab has made several key observations on the molecular mechanisms by which acantholysis proceeds in the human autoimmune blistering diseases pemphigus vulgaris and pemphigus foliaceus.  The presence or absence of adhesion represents a major biologic shift requiring coordination amongst various biological processes, including those regulating adhesion, migration, proliferation, differentiation, and cell death.  The intracellular regulatory and signalling events observed in pemphigus acantholysis likely represent variations of normal physiologic mechanisms regulating the presence/absence of desmosome-mediated cell-cell adhesion in epidermal epithelia.  We proposes that these events are important for regulating transitions in cell-adhesion and likely have a central role in adhesion transitions occuring during such processes as wound healing, tumor cell proliferation and invasion.  Current projects in the lab are focused on furthering work on the mechanism of pemphigus acantholysis as well as elucidating the role of desmosomes in wound healing and cancer biology.

Sancar, Aziz email , , , , , publications

We have three main areas of research focus: (1) Nucleotide excision repair: The only known mechanism for the removal of bulky DNA adducts in humans. (2) DNA damage checkpoints:  Biochemical pathways that transiently block cell cycle progression while DNA contains damage.  (3) Circadian rhythm:  The oscillations in biochemical, physiological and behavioral processes that occur with the periodicity of about 24 hours.

Searles, Lillie L. email , , publications

My lab is interested in mechanisms that (1) fine tune gene expression and (2) coordinate transcription and RNA processing in eukaryotes. Our work is based on molecular, genetic and biochemical analysis of the suppressor of sable gene of Drosophila.

Slep, Kevin email , , , , , , , publications

Our lab examines cytoskeletal dynamics, the molecules that regulate it and the biological processes it is involved in using live cell imaging, in vitro reconstitution and x-ray crystallography.  Of particular interest are the microtubule +TIP proteins that dynamically localize to microtubule plus ends, communicate with the actin network, regulate microtubule dynamics, capture kinetochores and engage the cell cortex under polarity-based cues.

Snider, Natasha email , , , , publications

Our lab has two areas of interest: the molecular basis of liver diseases and the biochemical mechanisms of disorders linked to intermediate filament gene mutations. We use biochemical, cell-based and in vivo approaches to identify potential disease targets and to understand their function and regulation. The major goal of our work is to promote the discovery of pharmacological agents that can slow or halt the progression of these diseases.

Sondek, John email , , , , , , publications

Our laboratory studies signal transduction systems controlled by heterotrimeric G proteins as well as Ras-related GTPases using a variety of biophysical, biochemical and cellular techniques. Member of the Molecular & Cellular Biophysics Training Program.

Stafford, Darrel W. email , , , publications

My laboratory at present is working on the vitamin K cycle and vitamin K-dependent proteins.  The enzymes of the vitamin K cycle include, at a minimum two integral membrane proteins, both of which were purified and cloned by my laboratory.  One, the vitamin K epoxide reductase is the target of warfarin for which 40 million prescriptions are written each year in the US alone.  Polymorphisms in this gene are the best example to date of the use of genomics in molecular medicine.  We are also interested in purifying any additional components of this cycle and trying to understand the ~50% of patients whose genotype is not informative about warfarin dose.  In addition, we are interested in the mechanism of how factor VIIa works and the role of the extracellular matrix in coagulation.

Strahl, Brian D. email , , , , , publications

Our laboratory is examining the role of histone post-translational modifications in chromatin structure and function.  Using a combination of molecular biology, genetics and biochemistry, we are determining how a number of modifications to the histone tails (e.g. acetylation, phosphorylation, methylation and ubiquitylation) contribute to the control of gene transcription, DNA repair and replication.

Tamayo, Rita email , , , , publications

Our lab studies the mechanisms facultative pathogens use to adapt to disparate and changing extracellular conditions. Our primary interest is in the ability of Vibrio cholerae, the causative agent of cholera, to persist in its native aquatic environment and also flourish in the host intestinal tract. We are addressing key questions about the role of cyclic diguanylate, a signaling molecule unique to and ubiquitous in bacteria, in the physiological adaptations of V. cholerae as it transits from the aquatic environment into a host. In addition, we are identifying and characterizing factors produced by V. cholerae during growth in a biofilm, a determinant of survival in aquatic environments, that contribute to virulence.  I will be accepting rotation students beginning in the winter of 2009.

Wang, Greg Gang email , , , , , publications

With an emphasis on chromatin biology and cancer epigenetics, our group focuses on mechanistic understandings of how chemical modifications of chromatin define distinct patterns of human genome, control gene expression, and regulate cell proliferation versus differentiation during development, and how their deregulations lead to oncogenesis. Multiple on-going projects employ modern biological technologies to: 1) biochemically isolate and characterize novel factors that bind to histone methylation on chromatin, 2) examine the role of epigenetic factors (chromatin-modifying enzymes and chromatin-associated factors) during development and tumorigenesis using mouse knockout models, 3) analyze epigenomic and transcriptome alternation in cancer versus normal cells utilizing next-generation sequencing technologies, 4) identify novel oncogenic or tumor suppressor genes associated with leukemia and lymphoma using shRNA library-based screening. We are also working together with UNC Center of Drug Discovery to develop small-molecule inhibitors for chromatin-associated factors as novel targeted cancer therapies.

Waters, Marcey email , , publications

Our research focuses on several different aspects of biomolecular recognition, including (1) protein post-translational modifications, (2) protein-nucleic acid interactions, and (3) protein-protein interactions that are important in a number of different biological areas, including epigenetics and cancer.  We use bio-organic chemistry combined with peptide design and biophysical chemistry to study these interactions and to develop new tools for inhibition and/or sensing of these biomolecular interactions.

Weeks, Kevin email , , , , , , publications

The Weeks group invents novel chemical microscopes for understanding the structure and function of RNA and then applies these technologies to leading, and previously intractable, problems in biology. Most projects in the laboratory span fundamental chemistry or technology development and ultimately lead to practical applications in virology (especially HIV), next-generation structure analysis, drug design, and understanding RNA structure in living cells.  Collectively, this work has led to extensive recognition of graduate student colleagues in the laboratory.

Weiss, Ellen email , , , , , , publications

The vertebrate retina is an extension of the central nervous system that controls visual signaling and circadian rhythm.  Our laboratory is interested in how the retina adapts to changing light intensities in the natural environment.  We are presently studying the regulation of 2 G protein-coupled receptor kinases, GRK1 and GRK7, that participate in signal termination in the light-detecting cells of the retina, the rods and cones.  Signal termination helps these cells recover from light exposure and adapt to continually changing light intensities.  Recently, we determined that GRK1 and GRK7 are phosphorylated by cAMP-dependent protein kinase (PKA).  Since cAMP levels are regulated by light in the retina, phosphorylation by PKA may be important in recovery and adaptation.  Biochemical and molecular approaches are used in 2 model organisms, mouse and zebrafish, to address the role of PKA in retina function. Keywords:  cAMP, cone, G protein-coupled receptor, GPCR, GRK, kinase, neurobiology, opsin, PKA, retina, rhodopsin rod, second messenger, signal transduction, vision.

Weissman, Bernard E. email , , , , , publications

How the loss of different components of the SWI/SNF complex contributes to neoplastic transformation remains an open and important question. My laboratory concentrates on addressing this question by the combined use of biological, biochemical and mouse models for SWI/SNF complex function.

Williams, David C. Jr. email , , , , publications

The overall objective of our research is to understand the connection between structure of protein-DNA complexes, protein dynamics and function.  We currently focus on the methyl-cytosine binding domain (MBD) family of DNA binding proteins.  The MBD proteins selectively recognize methylated CpG dinucleotides and regulate gene expression critical for both normal development and carcinogenesis.  We use a combination of NMR spectroscopy and biophysical analyses to study protein-DNA and protein-protein complexes involving the MBD proteins.  Building on these studies, we are developing inhibitors of complex formation as potential molecular therapeutics for b-hemoglobinopathies and cancer.

Wilson, Elizabeth M email , , , , , publications

Our research focus is on mechanisms of action of the androgen receptor (AR), a ligand-dependent transcriptional regulatory protein that mediates the effects of testosterone and dihydrotestosterone. Studies seek to identify and characterize AR coregulatory proteins and their regulation by phosphorylation and the cell cycle. Areas of interest include male sex development, the androgen insensitivity syndrome, and AR action in the ovary, endometrium and prostate cancer. Melanoma antigen gene protein-11 (MAGE-11) was identified as an AR coregulatory protein that belongs to the MAGE gene family of cancer-germline antigens. The MAGE-11 gene is located on the human X chromosome and is exclusively expressed in human and nonhuman primates, providing a gain-of- function to AR. Mechanisms whereby MAGE-11 regulates AR transcriptional activity through its interaction with the AR NH2-terminal FXXLF motif and cell cycle regulatory proteins are being investigated. Our objective is to understand how AR regulates gene transcription and cell proliferation in the human male and female reproductive tracts.  Keywords:  androgen receptor, MAGE-11, male reproduction, female reproduction, prostate cancer, transcription regulation, FXXLF motifs

Wolberg, Alisa email , , , , publications

We investigate cellular, molecular, and biochemical mechanisms of blood coagulation.  Using in vitro, ex vivo, and in vivo models, we focus on mechanisms contributing to cardiovascular disease (heart attack, stroke, deep vein thrombosis), including the effects of plasma proteins, cells, and blood flow (shear) on blood clot biochemical and mechanical stability.  We have shown that abnormalities in blood protein and/or cellular function contribute to bleeding and clotting pathologies including hemophilia and thrombosis, and shown how hemostatic and antithrombotic therapeutics modulate clot quality.  Current efforts are focused on pathophysiologic mechanisms that result in bleeding or prothrombotic disease (e.g., cancer).  Our overall goal is to translate this knowledge into novel approaches for treating bleeding and clotting disorders.

Wolfenden, Richard email , , publications

Enzymes allow organisms to channel the flow of matter to their own advantage, allowing some reactions to proceed rapidly compared with other reactions that offer no selective advantage to the organism. After a substrate is bound at an enzyme’s active site, its half-life is usually a small fraction of 1 s. Rapid turnover is necessary if any enzyme is to produce a significant rate of reaction at the limited concentration (<10(-5) M) at which enzymes are present within the cell. Many enzymes are known to have evolved to work nearly as efficiently as is physically possible, with second order rate constants that approach their rates of encounter (10(9) M(-1)s(-1) with the substrate in solution. How rapidly would biological reactions occur if an enzyme were not present? Until recently, some reactions were known to require several years, and everyday experience suggests that some reactions are slower still. The survival of paper documents and ancient ships for long periods under water implies that the glycosidic bonds of cellulose, for example, are very resistant to hydrolysis in the absence of cellulases that catalyze their hydrolysis. Why would one wish to know the rate of a biological reaction in the absence of an enzyme? That information would allow biologists to appreciate what natural selection has accomplished in the evolution of enzymes as proficient catalysts and would enable chemists to compare enzymes with artificial catalysts produced in the laboratory. Such information would also be of value in considering the design of enzyme antagonists: the greater the rate enhancement that an enzyme produces, the greater is its affinity for the altered substrate in the transition state compared with its relatively modest affinity for the substrate in the ground state. That principle has furnished a basis for the design of transition state analogues, extremely powerful inhibitors that resemble the transition state and take advantage of that special affinity. Examples have now been discovered for enzymes of every class, including inhibitors that are already used to control hypertension, the spread of HIV, the maturation of insects and the growth of weeds. By allowing snapshots of enzymes in action, transition state analogues have also provided valuable tools for investigating enzyme structures and mechanisms, most recently that of the peptide bond forming center of the ribosome. Those enzymes that produce the largest rate enhancements and transition state affinities should offer the most sensitive targets for inhibitor design. Particularly remarkable are those enzymes that act as simple protein catalysts, without the assistance of metals or other cofactors. To determine the extent to which one such enzyme, human uroporphyrinogen decarboxylase, enhances the rate of substrate decarboxylation; we examined the rate of spontaneous decarboxylation of pyrrolyl-3-acetate. Extrapolation of first-order rate constants measured at elevated temperatures indicates that this reaction proceeds with a half-life of 2.3 x 10(9) years, approaching the age of the Earth. This enzyme shows no significant structural or sequence homology with yeast orotidine 5′-monophosphate decarboxylase, another cofactorless enzyme that catalyzes a very slow reaction. To uncover the mechanisms of action of these remarkable molecules, we are studying these and other enzymes by kinetic and structural methods, site-directed mutation and the study of model reactions. In addition to more traditional methods, these projects make extensive use of new methods that include high-field NMR, isothermal calorimetry, and kinetic experiments in water and other solvents in sealed tubes at very high temperatures.

Zhang, Qi email , , , , publications

Our laboratory is focusing on developing and applying solution-state NMR methods, together with computational and biochemical approaches, to understand the molecular basis of nucleic acid functions that range from enzymatic catalysis to gene regulation. In particular, we aim to visualize, with atomic resolution, the entire dynamic processes of ribozyme catalysis, riboswitch-based gene regulation, and co-transciptional folding of mRNA. The principles deduced from these studies will provide atomic basis for rational manipulation of RNA catalysis and folding, and for de novo design of small molecules that target specific RNA signals. Research program in the laboratory provides diverse training opportunities in areas of spectroscopy, biophysics, structural biology, computational modeling, and biochemistry.

Zhang, Qing email , , , , , publications

The oxygen-sensing pathway contributes largely to the development of tumors. One of the central players in this pathway is prolyl hydroxylase (EglN1, 2 and 3). Our lab currently studies hypoxia signaling, prolyl hydroxylase and cancer, specifically breast and renal cell carcinoma. One project focuses on using proteomic and genomic approaches to screen for novel prolyl hydroxylase substrates that play important roles in cancer. The other project involves integrating CHIP-seq strategy with gene expression profiling in order to identify EglN2 prolyl hydroxylase and hypoxia inducible factor (HIF) targets in the malignant diseases. The ultimate goal is to understand mechanistically how oxygen-sensing pathways contribute to cancer progression, which will facilitate our design of efficient treatment strategies to specifically target cancer.

Zhang, Qisheng email , , , , publications

Our lab studies lipid signaling pathways that are involved in development and diseases by developing novel chemical probes and technologies. As key components of cellular membranes, lipids also serve as signaling molecules and modify functions of proteins through either covalent or non-covalent interactions. Dys-regulation of lipid signaling has been correlated with various diseases including cancer, diabetes, and neurodegenerative diseases. Consequently, many lipid-related proteins or processes have been used as therapeutic targets. However, lipids are dynamically metabolized and transported, making it difficult to illustrate the roles of lipids in development and diseases with limited availability of probes and technologies for lipid studies. The active projects in the lab include: 1) develop novel technologies to synthesize complex lipids, particularly phosphatidylinositides, and identify their interacting proteins in live cells; 2) develop new small molecule sensors and inhibitors for lipid metabolic enzymes such as PI3K and PLC; and 3) investigate cellular functions of lipids on different processes, particularly those regulated by small GTPases.