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The broad goal of our research is to understand basic mechanisms regulating erythropoiesis (red blood cell differentiation and maturation). Our current work focuses on a family of dual functional proteins (poly C binding proteins) which both regulate RNA processing and chaperone iron within cells. Using biochemical, cellular, and in vivo models we explore the cross talk between iron trafficking and RNA regulation mediated by poly C binding proteins and how these activities are modulated by disease.


Our lab is interested in the mechanisms of membrane trafficking in eukaryotic cells. Using a combination of biochemistry, in vitro reconstitution, and structural biology, we seek to understand how protein complexes assemble to bend and perturb membranes during vesicle budding (endocytosis) and vesicle fusion (exocytosis). Our group also specializes in cryo-electron microscopy (cryo-EM) and we use semi-native substrates (nanodiscs, liposomes) to visualize complexes engaged with the membrane.


Building a functioning brain requires an elaborate network of interactions between neurons and glia. We use mouse genetics, primary cell culture, quantitative proteomics, molecular biology, and super resolution microscopy to study glial cells during brain development. We are particularly interested in how astrocytes acquire their complex morphology and communicate with neighboring astrocytes, neurons, and oligodendrocytes. Furthermore, we are investigating how glial dysfunction drives the pathogenesis of brain disorders such as autism, schizophrenia, and leukodystrophy.


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.


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.


Our lab is interested in the molecular mechanisms of adaptive stress responses. These responses to environmental or metabolic stress are essential for survival but frequently dysregulated in disease. We use an integrated approach combining biophysical, structural, and biochemical methods to investigate the roles of intrinsically disordered proteins and dynamic enzymes that orchestrate these critical stress responses, with the ultimate goal of developing new approaches for modulating the functions of dynamic molecules.


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.


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.


We are studying tissue integrity and repair to develop innovative approaches for regenerative medicine and cancer prevention. We concentrate on highly regenerative (endometrial and intestinal) tissues and are particularly interested in how persistent inflammation influences the breakdown of biochemical pathways that oversee genome stability, stem cell plasticity, and cell adhesions and how these events influence future tissue repair and onset of disease, such as cancer. Projects employ a variety of molecular, cellular, biochemical, genetic, and machine learning techniques that span across cell culture systems, genetically engineered mouse models, and human tissues to understand the impact of acute and chronic inflammation on cell division, cytoskeletal dynamics, and DNA repair in regenerating epithelial cells.


Our research group uses several biochemical and structural techniques (e.g. enzyme assays, X-ray crystallography, and cryo-EM) to understand how molecular machines drive the cell cycle. Dysregulation of these enzymes results in numerous cancer types.


A growing body of work in the biomedical sciences generates and analyzes omics data; our lab’s work contributes to these efforts by focusing on the integration of different omics data types to bring mechanistic insights to the multi-scale nature of cellular processes. The focus of our research is on developing systems genomics approaches to study the impact of genomic variation on genome function. We have used this focus to study genetic and molecular variation in both natural and engineered cellular systems and approach these topics through the lens of computational biology, machine learning and advanced omics data integration. More specifically, we create methods to reveal functional relationships across genomics, transcriptomics, ribosome profiling, proteomics, structural genomics, metabolomics and phenotype variability data. Our integrative omics methods improve understanding of how cells achieve regulation at multiple scales of complexity and link to genetic and molecular variants that influence these processes. Ultimately, the goal of our research is advancing the analysis of high-throughput omics technologies to empower patient care and clinical trial selections. To this end, we are developing integrative methods to improve mutation panels by selecting more informative genetic and molecular biomarkers that match disease relevance.


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.


The Button lab in the Department of Biochemistry and Biophysics is part of the Marsico Lung Institute. Our lab is actively involved in projects that are designed to define the pathogenesis of muco-obstructive pulmonary disorders and to identify therapies that could be used to improve the quality of life in persons afflicted by these diseases. In particular, our research works to understand the biochemical and biophysical properties of mucin biopolymers, which give airway mucus its characteristic gel-like properties, and how they are altered in diseases such as Asthma, COPD, and cystic fibrosis.


Our laboratory now studies mechanisms of genome replication and pathogenesis of respiratory enteroviruses and evolution of neurovirulence using the tools of mechanistic enzymology, cell biology, stem-cell engineering, and virology. Our laboratory is also pioneering the development of tools to monitor viral infection dynamics on the single-cell level, aka “single-cell virology.”


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.


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.


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.


Lipids are crucial molecules for life. They play important roles in building membranes, storing energy, and cell signaling. We are interested in how lipids move around both within cells and between cells, for example from astrocytes to neurons. The lab uses cutting-edge microscopy techniques including live-cell imaging, superresolution microscopy, and multispectral imaging. We use these approaches to understand how defects in lipid trafficking contribute to metabolic and neurodegenerative diseases.


Males and females differ in their prelevance, treatment, and survival to a diverse set of human disease states. This is exemplified cardiovascular disease, a disease that takes more lives than all forms of cancer combined. In cardiac disease, women almost uniformly fare far worse than men: as of 2007 one woman dying for cardiovascular disease in the US every minute. Our lab focuses on sex disparities in development and disease. For these studies, we use a highly integrated approach that incorporates developmental, genetic, proteomic, biochemical and molecular-based studies in mouse and stem cells. Recent advances by our past students (presently at Harvard, John Hopkins and NIH) include studies that define the cellular and molecular events that lead to cardiac septation, those that explore cardiac interaction networks as determinants of transcriptional specificity, the mechanism and function of cardiac transcriptional repression networks, and the regulatory networks of cardiac sexual dimorphism. Our lab has opening for rotation and PhDs to study these rapidly emerging topics.


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.


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.


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.


Sleep is an essential and evolutionarily conserved process that modifies synapses in the brain to support cognitive functions such as learning and memory. We are interested in understanding the molecular mechanisms of synaptic plasticity with a particular interest in sleep. Using mouse models of human disease as well as primary cultured neurons, we are applying this work to understanding and treating neurodevelopmental disorders including autism and intellectual disability. The lab focuses on biochemistry, pharmacology, animal behavior and genetics.


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.


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.


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.


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.


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


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.


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 human placenta is the first organ to develop after fertilization and is the least studied! We hope to change this by using a multidisciplinary approach. From iPSC-derived trophoblasts in culture to mouse models and human placenta tissue, the Placental Cell Biology Group at NIEHS answers fundamental questions about placenta cell and developmental biology. Our lab uses a range of microscopy (cryo-EM, fluorescence), recombinant protein production, and -omics techniques. The goal of our research is to understand how autophagy controls placenta development, differentiation, and function.


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.


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.


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
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Nutrition

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.


My research focus pertains to vascular remodeling as it relates to the pathogenesis and progression of thoracic aortic aneurysms. Using murine and porcine models, as well as human aneurysm tissue samples, we study proteinase and signaling biology with a view towards defining novel modalities targets for diagnosis, tracking, risk stratification and non-surgical treatment of this devastating disease.


James, Lindsey Ingerman
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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.


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.


Antiretroviral therapy (ART) is effective in suppressing HIV-1 replication in the periphery, however, it fails to eradicate HIV-1 reservoirs in patients. The main barrier for HIV cure is the latent HIV-1, hiding inside the immune cells where no or very low level of viral particles are made. This prevents our immune system to recognize the latent reservoirs to clear the infection. The main goal of my laboratory is to discover the molecular mechanisms how HIV-1 achieves its latent state and to translate our understanding of HIV latency into therapeutic intervention.

Several research programs are undertaking in my lab with a focus of epigenetic regulation of HIV latency, including molecular mechanisms of HIV replication and latency establishment, host-virus interaction, innate immune response to viral infection, and the role of microbiome in the gut health. Extensive in vitro HIV latency models, ex vivo patient latency models, and in vivo patient and rhesus macaque models of AIDS are carried out in my lab. Multiple tools are applied in our studies, including RNA-seq, proteomics, metabolomics, highly sensitive digital droplet PCR and tissue RNA/DNAscope, digital ELISA, and modern and traditional molecular biological and biochemical techniques. We are also very interested in how non-CD4 expression cells in the Central Nervous System (CNS) get infected by HIV-1, how the unique interaction among HIV-1, immune cells, vascular cells, and neuron cells contributes to the initial seeding of latent reservoirs in the CNS, and whether we can target the unique viral infection and latency signaling pathways to attack HIV reservoirs in CNS for a cure/remission of HIV-1 and HIV-associated neurocognitive disorders (HAND). We have developed multiple tools to attack HIV latency, including latency reversal agents for “Shock and Kill” strategy, such as histone deacetylase inhibitors and ingenol family compounds of protein kinase C agonists, and latency enforcing agents for deep silencing of latent HIV-1. Several clinical and pre-clinical studies are being tested to evaluate their potential to eradicate latent HIV reservoirs in vivo. We are actively recruiting postdocs, visiting scholars, and technicians. Rotation graduate students and undergraduate students are welcome to join my lab, located in the UNC HIV Cure Center, for these exciting HIV cure research projects.


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.


One of the main focuses of my work is the characterization of the large mucin gene products (Mr 2-3 million) and the complexes they make (Mr 10-100 million) essential for the formation of the mucus gels vital for epithelial protection and function. My current work is focused around the human lung, where there are many hypersecretory human diseases, including asthma, cystic fibrosis, and chronic bronchitis, in which these glycoconjugates are centrally implicated. Basic understanding of the qualitative and quantitative changes of mucin macromolecules in lung health and diseases is our main task.


Knight, Abigail
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Chemistry

The Knight group focuses on designing novel macromolecular materials with functions inspired by biological systems. These materials will generate platforms of new biomimetic polymeric architectures addressing growing concerns in treating, diagnosing, and preventing human disease. This research bridges the fields of chemical biology and polymer chemistry using characterization and synthetic tools including polymer and solid-phase synthesis and nanomaterial characterization. Specific project areas include: (1) developing a new class of peptide-polymer amphiphiles inspired by metalloproteins, (2) designing well-defined polymer bioconjugates for biosensing, and (3) evolving functional biomimetic polymers.


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.


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.


We focus on a variety of design goals including the creation of novel protein-protein interactions, protein structures, vaccine antigens and light activatable protein switches. Central to all of our projects is the Rosetta program for protein modeling. In collaboration with developers from a variety of universities, we are continually adding new features to Rosetta as well as testing it on new problems.


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.


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.


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.


My research has focused on developing new radio-chemistry, imaging probes, and therapeutic approaches including nanomedicine for various diseases. Most importantly, we have the culture of forming an active collaboration with people in different field. With a cGMP lab located within our facility, we are also experienced on developing lead agents and translate it to clinic.


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.


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.


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.


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


Lockett, Ryen Matthew
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PHD PROGRAM
Chemistry

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.


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.


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.


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.


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.


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.


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.


The Nguyen lab develops the next generation of effective and safe biotherapeutics for life-threatening diseases such as cancer and myocardial infarction. We engineer novel immunomodulatory carriers based on genetically encoded materials and lipids that home to the site of disease, respond to changes in the microenvironment, and effectively deliver nucleic acids and drugs.


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.


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.


Cell adhesion, cytoskeletal regulation and Wnt signaling in development and cancer
The Peifer lab works at the interface between cell, developmental, and cancer biology, focusing on the epithelial tissues that form the basic architectural unit of our bodies and of those of other animals. We explore how the machinery mediating cell adhesion, cytoskeletal regulation and Wnt signaling regulates cell fate and tissue architecture in development and disease. We take a multidisciplinary approach, spanning genetics, cutting edge cell biology including super-resolution microscopy, biochemistry and computational approaches. We use the fruit fly Drosophila as an animal model and combine that with work in cultured normal and colorectal cancer cells. Possible thesis projects include exploring how connections between cell junctions and the cytoskeleton are remodeled to allow cells to change shape and move without tearing tissues apart or exploring how the tumor suppressor protein APC assembles a multi-protein machine that negatively regulates Wnt signaling and how this goes wrong in colorectal tumors. I am a hands on-mentor with an open-door policy and my office is in the lab. I value and advocate for diversity. Our lab has a strong record of training PhD students and postdocs who move on to success in diverse science-related careers. Our lab is funded by a long-standing NIH grant that extends to July 2021, and just received a good score for renewal. To learn more about or research, our recent publications, our team and our alumni check out the lab website at: https://proxy.qualtrics.com/proxy/?url=http%3A%2F%2Fpeiferlab.web.unc.edu%2F&token=1rPNJvHEEfhAAiwkSviuOG0Fg8%2ByN3Q3GMob1A2GJwM%3D


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.


Our research is focused on RNA-binding proteins and their physiopathological roles. An understudied aspect of human disease is gene regulation by modulation of mRNA function. In our research lab we investigate functional connections between the RNA-binding protein Zinc Finger Protein 36 Like-2 (ZFP36L2 or L2) and human diseases. L2 is a member of the Tris-Tetra-Proline or Zinc Finger Protein 36 (TTP/ZFP36) family of RNA-binding proteins that bind Adenine-uridine-Rich Elements (AREs) in the 3’ untranslated regions of target mRNAs. Upon binding, L2 accelerates mRNA target degradation and/or inhibits mRNA translation, ultimately decreasing the protein encoded by the L2-target mRNA.

We have three particular goals:

  • Determine new specific L2-mRNA targets involved in human diseases.
  • Determine the mechanism(s) by which L2 modulates these novel RNA targets.
  • Determine the physiological consequences of L2 ablation in specific cells types using mouse models and CRISPR/Cas9-mediated knockout system.

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.


We are interested in unraveling the molecular basis for human disease and discover new treatments focused on human and microbial targets. Our work extends from atomic-level studies using structural biology, through chemical biology efforts to identify new drugs, and into cellular, animal and clinical investigations. While we are currently focused on the gut microbiome, past work has examined how drugs are detected and degraded in humans, proteins designed to protect soldiers from chemical weapons, how antibiotic resistance spreads, and novel approaches to treat bacterial infections. The Redinbo Laboratory actively works to increase equity and inclusion in our lab, in science, and in the world. Our lab is centered around collaboration, open communication, and trust. We welcome and support anyone regardless of race, disability, gender identification, sexual orientation, age, financial background, or religion. We aim to: 1) Provide an inclusive, equitable, and encouraging work environment 2) Actively broaden representation in STEM to correct historical opportunity imbalances 3) Respect and support each individual’s needs, decisions, and career goals 4) Celebrate our differences and use them to discover new ways of thinking and to better our science and our community


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.


The Shaikh lab aims to understand how differing dietary fatty acids regulate outcomes associated with immunity and metabolism in the context of obesity, type 2 diabetes, and cardiovascular diseases. The lab conducts studies at the human level and in mouse models.  We are currently focused on the mechanisms by which omega-3 fatty acids improve chronic inflammation and humoral immunity upon viral infection in obesity. We are also elucidating how select fatty acids disrupt the biophysical organization of the inner mitochondrial membrane of differing cell types and thereby respiratory activity.


The Singleton Laboratory is interested in understanding the molecular basis for the develoment and transmission of microbial drug resistance and the discovery and exploitation of new strategies for controlling drug-resistant microorganisms. We develop and adapt synthetic chemistry and synthetic biology methods to provide new molecular tools — both biologically active small molecules and innovative platforms — for hypothesis-driven biological research and pharmaceutical discovery. These foundations of our program offers both chemically-oriented and biologically-oriented researchers new opportunities for the development of integrated, multi-disciplinary knowledge and technologies.


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.


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.


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.


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.


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.


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
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Chemistry

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.


One of the most amazing discoveries of recent years has been the profound role of RNA in regulating all areas of biology. Further, the functions of many RNA molecules require that an RNA fold back on itself to create intricately and complexly folded structures. Until recently, however, we had little idea of the broad contributions of RNA structure and function because there simply did not exist rigorous methods for understanding RNA molecules in cells and viruses. The vision of our laboratory is therefore, first, to invent novel chemical microscopes that reveal quantitative structure and function interrelationships for RNA and, second, to apply these RNA technologies to broadly important problems in biology. Mentoring and research in the lab are highly interdisciplinary. Students learn to integrate ideas and concepts spanning chemical and computational biology, and technology development, and extending to practical applications in virology, understanding biological processes in cells, and discovery of small molecule ligands targeted against medically important RNAs. Each student has a distinct project which they drive to an impactful conclusion, but do so as part of the lab team which, collectively, has shown an amazing ability to solve big problems in RNA biology. The overarching goal of mentoring in the lab is to prepare students for long-term leadership roles in science.


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.


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.


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.


We investigate mechanisms in blood coagulation and diseases that intersect with abnormal blood biomarkers and function, including cardiovascular disease (heart attack, stroke, deep vein thrombosis, pulmonary embolism), bleeding (hemophilia), inflammation, obesity, and cancer. We also investigate established drugs and new drugs in preclinical development to understand their role in reducing and preventing disease. Our studies use interdisciplinary techniques, including in vitro, ex vivo, and in vivo mouse models and samples from humans in translational studies that span clinic to bench. Our lab emphasizes a culture of diversity, responsibility, independence and collaboration, and shared excitement for scientific discovery. We are located in the UNC Blood Research Center in the newly-renovated Mary Ellen Jones building.


The Yan lab works at the interface of material science, photonics, and biology. We synthesize metal, metal oxide and upconversion nanoparticles for biophotonics and biomedicine applications. We use holographic optical tweezers and atomic force microscope (AFM) to trap and manipulate single nanoparticles, and use them as probes to study nano-bio interactions, including biosensing, bionanomechanics and cell biology. We conduct these studies with a customized multi-modal correlative optical system that combines the nanomanipulation module with advanced optical microscopy and spectroscopy techniques.


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.


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.