Faculty Database:
[Research Interest: Cell Biology]

Filter faculty by:
See All
NameEmailPhd ProgramResearch InterestsPublications
Amelio, Antonio L. email , , , , , , , publications

Our laboratory is broadly interested in understanding the molecular mechanisms of transcriptional regulation by cell signaling pathways and the role of pathway cross-talk in cancer biology. In particular, the cAMP signaling cascade directs adaptive cellular responses to a variety of stress stimuli via a combination of acute affects arising from GS-protein coupled receptor (GPCR)-mediated activation of PKA and long-term affects resulting from transcriptional reprogramming directed by CREB and the CREB Regulated Transcription Coactivators (CTRCs). We are applying an interdisciplinary approach to study the consequences of aberrant activation of the cAMP/CREB/CRTC signal circuit on these adaptive responses and how cooperative signaling with other pathways promotes oncogenic processes in oral, head, and neck cancers.

Anton, Eva email , , , , , publications

Laminar organization of neurons in cerebral cortex is critical for normal brain function. Two distinct cellular events guarantee the emergence of laminar organization– coordinated sequence of neuronal migration, and generation of radial glial cells that supports neurogenesis and neuronal migration. Our goal is to understand the cellular and molecular mechanisms underlying neuronal migration and layer formation in the mammalian cerebral cortex. Towards this goal, we are studying the following three related questions: 1. What are the signals that regulate the establishment, development and differentiation of radial glial cells, a key substrate for neuronal migration and a source of new neurons in cerebral cortex?2. What are the signals for neuronal migration that determine how neurons reach their appropriate positions in the developing cerebral cortex?3. What are the specific cell-cell adhesion related mechanisms that determine how neurons migrate and coalesce into distinct layers in the developing cerebral cortex?

Arendshorst, William email , , , , publications

We study mechanisms of cellular and molecular function as they control cardiovascular and kidney physiology in health and disease. We focus on G-protein coupled receptors and calcium signaling pathways of resistance arterioles that regulate vascular resistance in normal kidneys and pathophysiologically such as those of animals with genetic hypertension or animals with genes deleted. Measurements include renal vascular reactivity to neurohormonal agents and autacrine/paracrine factors combined with parallel investigation of receptor/calcium signal transduction in vascular smooth muscle cells in vitro.

Bahnson, Edward Moreira email , , , , , , publications

We are interested in studying diabetic vasculopathies. Patients with type 2 diabetes mellitus or metabolic syndrome have aggressive forms of vascular disease, possessing a greater likelihood of end-organ ischemia, as well as increased morbidity and mortality following vascular interventions. Our long term research aims to change the way we treat arterial disease in diabetes by:

  • Understanding why arterial disease is more aggressive in diabetic patients, with a focus in redox signaling in the vasculature.
  • Developing targeted systems using nanotechnology to locally deliver therapeutics to the diseased arteries.
Baldwin, Albert S. email , , , , , , publications

Our laboratory studies an amazing regulatory factor known as NF-kappaB. This transcription factor controls key developmental and immunological functions and its dysregulation lies at the heart of virtually all major human diseases.

Bautch, Victoria email , , , , , , publications

Blood vessel formation in cancer and development; use mouse culture (stem cell derived vessels) and in vivo models (embryos and tumors); genetic, cell and molecular biological tools; how do vessels assemble and pattern?, dynamic image analysis.

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.

Bloom, Kerry email , , , , , , publications

Our objective is to understand the dynamic and structural properties of chromosomes during mitosis.  We use live cell imaging techniques to address how kinetochores are assembled, capture microtubules and promote faithful segregation of chromosomes.

Brenman, Jay email , , , , , , publications

The Brenman lab studies how a universal energy and stress sensor, AMP-activated protein kinase (AMPK) regulates cellular function and signaling.  AMPK is proposed to be a therapeutic target for Type 2 diabetes and Metabolic syndrome (obesity, insulin resistance, cardiovascular disease). In addition, AMPK can be activated by LKB1, a known human tumor suppressor. Thus AMPK signaling is not only relevant to diabetes but also cancer.  We are interested in molecular genetic and biochemical approaches to understand how AMPK contributes to neurodegeneration, metabolism/cardiac disease and cancer.

Brennwald, Patrick email , , , , , publications

We are interested in the mechanism by which eukaryotic cells are polarized and the role of vesicle transport plays in the determination and regulation of cell polarity and tumorigenesis.

Bressan, Michael email , , , , publications

Oscillatory behaviors are seen at multiple scales throughout biology and fundamentally require both a biochemical process capable of sustained, repetitive, state transitions and a system to functionally interpret each state. Multicellular organ systems routinely utilize such biorhythmic electrochemicaloscillators to coordinate and order physiological processes. Or group’s primary research interests are focused on: i) the developmental mechanisms that specify autonomous rhythmic signal generation, and ii) the cellular and biophysical processes that allow for effective downstream transmission of these signals.   To address these topics we combine classical experimental embryological approaches with state-of-the-art live cell imaging to investigate the physiological development of the electrical system of the heart.

Calabrese, J. Mauro email , , , , , , , , , publications

Our lab is trying to understand the mechanisms by which long noncoding RNAs orchestrate the epigenetic control of gene expression. Relevant examples of this type of gene regulation occur in the case of X-chromosome inactivation and autosomal imprinting. We specialize in genomics, but rely a combination of techniques —  including genetics, proteomics, and molecular, cell and computational biology — to study these processes in both mouse and human stem and somatic cell systems.

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.

Cheney, Richard email , , , , , , publications

Our goal is to understand the fundamental cell biology underlying processes such as neurodevelopment, angiogenesis, and the metastasis of cancer cells.  Most of our experiments focus on molecular motors such as myosin-X and on the finger-like structures known as filopodia.  We generally utilize advanced imaging techniques such as TIRF and single-molecule imaging in conjunction with mammalian cell culture.  We also  use molecular biology and biochemistry and are in the process of developing a mouse model to investigate the functions of myosin-X and filopodia.   We are looking for experimentally driven students who have strong interests in understanding the molecular basis of dynamic cellular processes such as filopodial extension, mechanosensing, and cell migration.

Clemmons, David R email , , , , , , publications

Cross-talk between insulin like growth factor -1 and cell adhesion receptors in the regulation of cardiovascular diseases and complications associated with diabetes.

Cohen, Sarah email , , , publications

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.

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.

Coleman, William B. email , , , , , publications

The research in our laboratory involves several major projects related to the molecular pathogenesis of human cancer and investigations related to the biology of liver stem-like progenitor cells, including (i) characterization of human liver tumor suppressor genes, (ii) analysis of genetic determinants of breast cancer, (iii) investigation of mechanisms governing aberrant DNA methylation in breast cancer, (iv) liver progenitor cell responses after toxic liver injury, and (v) transplantation of liver stem-like progenitor cells for correction of genetic liver disease.

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.

Costello, Joe email , , , , , publications

The main research project is to determine the role of intercellular junctions in normal development, cell aging and cataract formation in human and animal lenses.

Cox, Adrienne email , , , , , , publications

Our lab is interested in molecular mechanisms of oncogenesis, specifically as regulated by Ras and Rho family small GTPases. We are particularly interested in understanding how membrane targeting sequences of these proteins mediate both their subcellular localization and their interactions with regulators and effectors. Both Ras and Rho proteins are targeted to membranes by characteristic combinations of basic residues and lipids that may include the fatty acid palmitate as well as farnesyl and geranylgeranyl isoprenoids. The latter are targets for anticancer drugs; we are also investigating their unexpectedly complex mechanism of action. Finally, we are also studying how these small GTPases mediate cellular responses to ionizing radiation – how do cells choose whether to arrest, die or proliferate?

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.

Darville, Lee Antoinette (Toni) email , , , , publications

Research in the Darville lab is focused on increasing our understanding of immune signaling pathways active in development of genital tract disease due to Chlamydia trachomatis and determination of chlamydial antigen-specific T cell responses that lead to protection from infection and disease. In vitro, murine model, and human studies are being performed with the ultimate goal to develop a vaccine against this prevalent sexually transmitted bacterial pathogen. Genetic and transcriptional microarray studies are being performed to explore pathogenic mechanisms and determine biomarkers of pelvic inflammatory disease due to Chlamydia as well as other sexually transmitted pathogens.

de Silva, Aravinda email , , , , publications

We study Borrelia burgdorferi (the agent of Lyme disease) as a model for understanding arthropod vector-borne disease transmission. We also study the epidemiology and pathogenesis of dengue viruses associated with hemorrhagic disease.

Der, Channing email , , , , , , , publications

Our research centers on understanding the molecular basis of human carcinogenesis. In particular, a major focus of our studies is the Ras oncogene and Ras-mediated signal transduction.  The goals of our studies include the delineation of the complex components of Ras signaling and the development of anti-Ras inhibitors for cancer treatment.  Another major focus of our studies involves our validation of the involvement of Ras-related small GTPases (e.g., Ral, Rho) in cancer.  We utilize a broad spectrum of technical approaches that include cell culture and mouse models, C. elegans, protein crystallography, microarray gene expression or proteomics analyses, and clinical trial analyses.

Deshmukh, Mohanish email , , , , , , publications

We study how mammalian cells regulate their survival and death (apoptosis).  We have focused our work on identifying unique mechanisms by which these pathways are regulated in neurons, stem cells, and cancer cells.  We utilize various techniques to examine this in primary cells as well as in transgenic and knock out mouse models in vivo.  Our ultimate goal is to discover novel cell survival and death mediators that can be targeted for therapy in neurodegeneration and cancer.

Doerschuk, Claire M email , , , , publications

We study host defense mechanisms in the lungs, particularly the inflammatory and innate immune processes important in the pathogenesis and course of bacterial pneumonia, acute lung injury/acute respiratory distress syndrome, and cigarette smoke-associated lung disease. Basic and translational studies address mechanisms of host defense, including recruitment and function of leukocytes, vascular permeability leading to edema, bacterial clearance and resolution.  Cell signaling pathways initiated by binding of leukocyte-endothelial cell adhesion molecules and molecular mechanisms underlying the functions of neutrophils are two particular areas.

Duronio, Bob email , , , , , publications

My lab studies how cell proliferation is controlled during animal development, with a focus on the genetic and epigenetic mechanisms that regulate DNA replication and gene expression throughout the cell cycle. Many of the genes and signaling pathways that we study are frequently mutated in human cancers. Our current research efforts are divided into three areas:  1) Plasticity of cell cycle control during development  2) Histone mRNA biosynthesis and nuclear body function  3) Epigenetic control of genome replication and function

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.

Everett, Eric T email , , , , , publications

Our research focuses upon craniofacial and mineralized tissue genetics; gene: environment interactions; mapping of complex traits; normal variation (to the extent that normal variation becomes abnormal); and animal models for oral/dental/craniofacial disorders.

Falk, Ronald J. email , , , publications

As the Director of the UNC Kidney Center, the scope of Dr. Falk’s research interests spans many disciplines, including molecular biology, immunology, genetics, pathology, cell biology, protein chemistry, epidemiology, pharmacokinetics and biostatistics. Dr. Falk is recognized world wide as a leader in research on kidney diseases related to autoimmune responses. He works closely with the basic research scientists within the UNC Kidney Center, including Dr. Gloria Preston, thus this research program provides an environment for Translational Research within the UNC Kidney Center.

Giudice, Jimena email , , , , , publications

During development transcriptional and posttranscriptional networks are coordinately regulated to drive organ maturation, tissue formation, and cell fate. Interestingly, more than 90% of the human genes undergo alternative splicing, a posttranscriptional mechanism that explains how one gene can give rise to multiple protein isoforms. Heart and skeletal muscle are two of the tissues where the most tissue specific splicing takes place raising the question of how developmental stage- and tissue-specific splicing influence protein function and how this regulation occurs. In my lab we are interested on two exciting aspects of this broad question: i) how alternative splicing of trafficking and membrane remodeling genes contributes to muscle development, structure, and function, ii) the coupling between epigenetics and alternative splicing in postnatal heart development.

Gladfelter, Amy email , , , , , publications

We study large multinucleate cells such as fungi, muscle and placenta to understand how cells are organized in time and space.  Using quantitative live cell microscopy, biochemical reconstitution and computational approaches we examine how the physical properties of molecules generate spatial patterning of cytosol and scaling of cytoskeleton scaffolds in the cell cycle.

Goldstein, Bob email , , , , , , publications

We address fundamental issues in cell and developmental biology, issues such as how cells move to specific positions, how the orientations of cell divisions are determined, how the mitotic spindle is positioned in cells, and how cells respond to cell signaling – for example Wnt signaling, which is important in development and in cancer biology. We are committed to applying whatever methods are required to answer important questions. As a result, we use diverse methods, including methods of cell biology, developmental biology, forward and reverse genetics including RNAi, biochemistry, biophysics, mathematical and computational modeling and simulations, molecular biology, and live microscopy of cells and of the dynamic components of the cytoskeleton – microfilaments, microtubules, and motor proteins. Most experiments in the lab use C. elegans embryos, and we have also used Drosophila and Xenopus recently. C. elegans is valuable as a model system because of the possibility of combining the diverse techniques above to answer a wide array of interesting questions. We also have a project underway to develop a new model system for studying how cellular and developmental mechanisms evolve, using little-studied organisms called water bears. Rotating graduate students learn to master existing techniques, and students who join the lab typically grow their rotation projects into larger, long term projects, and/or develop creative, new projects.

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.

Gulati, Ajay email , , , , publications

The work of our laboratory is focused on understanding interactions between the commensal microbiota of the gut and the host epithelium, particularly in the context of chronic inflammatory conditions such as inflammatory bowel diseases (IBD).  Specifically, we are interested in determining the mechanisms by which various susceptibility genes for IBD affect the structure and function of the intestinal microbiota.  In particular, we are exploring the mechanisms by which IBD risk alleles alter the function of intestinal epithelial cells including Paneth, goblet, and stem cells. We expect these studies will lead to the development of safer, patient-specific therapies for individuals with IBD.

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.

Han, Zongchao email , , , , publications

My research focus centers on retinal gene/drug therapy using nanotechnologies. My laboratory is interested in developing gene therapies for inherited blinding diseases and eye tumors. We are particularly interested in understanding the gene expression patterns that are regulated by the cis-regulatory elements. We utilize compacted DNA nanoparticles which have the ability to transfer large genetic messages to overcome various technical challenges and to appreciate the translational potential of this technology. This multidimensional technology also facilitated targeted drug delivery. Currently, we are working on the design and development of several specific nano formulations with targeting, bioimaging and controlled release specificities.

Hathaway, Nathaniel A. email , , , , , publications

The Hathaway lab is focused on understanding the biological events responsible for dynamically regulating the selective expression of the mammalian genome. In multicellular organisms, genes must be regulated with high precision during stem cell differentiation to achieve normal development. Pathologically, the loss of proper gene regulation caused by defects in chromatin regulatory enzymes has been found to be a driving force in cancer initiation and progression. My lab uses a combination of chemical biology and cell biology approaches to unravel the molecular mechanisms that govern gene expression. We utilize new tools wielding an unprecedented level of temporal control to visualize changes in chromatin structure and function in mammalian cells and animal models. In addition, we seek to identify small molecule inhibitors that are selective for chromatin regulatory enzymes with the potential for future human therapeutics.

Homeister, Jonathon W. email , , , , publications

Our research focuses on understanding the molecular and cellular mechanisms of leukocyte (white blood cell) trafficking and homing in vascular inflammation and immune responses. We are interested in the glycobiology of the Selectin leukocyte adhesion molecules and their ligands, and understanding the roles for these glycoproteins in the pathogenesis of inflammatory/immune cardiovascular diseases such as atherosclerosis and vasculitis. We are also interested in the mechanisms whereby the selectins and their ligands link the inflammatory response and coagulation cascade and thereby modulate thrombosis and hemostasis.

Hunter, E. Sidney email , , publications

Our research focuses on determining the mechanisms responsible for craniofacial birth defects. We use the whole embryo culture system to expose mouse conceptuses to toxicants and evaluate morphological, molecular (Affy arrays) and protein changes. Antisense morpholinos and adenoviruses are used to modulate gene expression and determine phenotypic effects.  We are using embryonic stem cells as a model to evaluate the effects of environmental chemicals on differentiation. Using molecular markers to identify differentiation may provide critical information to identify developmental toxicants.

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.

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.

Kaufman, David G. email , , , , , publications

Topic 1  We seek genomic targets for carcinogenesis among segments of DNA replicated in early S phase when cells are most susceptible to carcinogens.  We are mapping genomic sites replicated during early S phase, identifying origins of replication activated in this interval, and characterizing temporal sequencing of replication from these origins.  Topic 2  We are reconstructing differentiated and functional human endometrial tissue from epithelial and stromal cells interacting in culture.  We use these co-cultures to study development of endometrial cancer.

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.

Kim, WIlliam Y email , , , , , publications

Our research explores the role of hypoxia-inducible factor (HIF) in tumorigenesis. HIF is a transcription factor that plays a key role in oxygen sensing, the adaptation to hypoxia and the tumor microenvironment. It is expressed in the majority of solid tumors and correlates with poor clinical outcome. Therefore, HIF is a likely promoter of solid tumor growth and angiogenesis.  Our lab uses mouse models to ask if and how HIF cooperates with other oncogenic events in cancer.  We are currently investigating HIF’s role in the upregulation of circulating tumor cells and circulating endothelial cells.

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.

Lawrence, David S email , , , , , , publications

Living cells have been referred to as the test tubes of the 21st century. New bioactive reagents developed in our lab are designed to function in cells and living organisms. We have prepared enzyme inhibitors, sensors of biochemical pathways, chemically-altered proteins, and activators of gene expression. In addition, many of these agents possess the unique attribute of remaining under our control even after they enter the biological system. In particular, our compounds are designed to be inert until activated by light, thereby allowing us to control their activity at any point in time.

Liu, Jiandong email , , , , , publications

Congenital heart diseases are one of the most common birth defects in humans, and these arise from developmental defects during embryogenesis.  Many of these diseases have a genetic component, but they might also be affected by environmental factors such as mechanical forces. The Liu Lab combines genetics, molecular and cell biology to study cardiac development and function, focusing on the molecular mechanisms that link mechanical forces and genetic factors to the morphogenesis of the heart.  Our studies using zebrafish as a model system serve as the basic foundation to address the key questions in cardiac development and function, and could provide novel therapeutic interventions for cardiac diseases.

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, Zhi email , , , , publications

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

Loeser, Richard F. email , , , , publications

The Loeser lab uses a combination of in vitro studies in articular chondrocytes and in vivo studies in mice to examine molecular mechanisms of joint tissue destruction in aging and osteoarthritis. A major focus of this work is examining how reactive oxygen species regulate cell signaling through oxidation of Cys residues in specific kinases and phosphatases. Pathways of interest include integrin mediated signaling that stimulates matrix metalloproteinase (MMP) expression and IGF-I signaling that stimulates matrix production. Oxidative stress disrupts the balance in the activity of these pathways to favor matrix destruction over repair contributing to the development of osteoarthritis.

Lorenzo, Damaris N. email , , , , , publications

Cytoskeletal-associated proteins are critical for the maintenance of cellular homeostasis, and their involvement in cancer and in numerous neurodegenerative, neurodevelopmental, psychiatric, heart, muscular, and metabolic disorders underscores their functional relevance.

Our lab investigates the contribution of the cytoskeleton to key physiological processes and the mechanistic basis of cytoskeleton-associated disorders. Our goal is to understand the roles of cytoskeletal proteins in the regulation of cellular dynamics and bioenergetics in metabolically active tissues as well as their involvement in brain development and connectivity. Our initial efforts focus on the ankyrin and spectrin families of cytoskeletal-associated proteins, which deficits have direct implications in the regulation of cell migration, in metabolic disorders such as obesity and diabetes, and may also underlie neurological diseases, including spinocerebellar ataxias, autism and West syndrome.

We combine human genetics, cellular and biochemistry approaches with Omics technologies and high resolution imaging-based assays in primary cells and in animal models of development and human disease.

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.

Maddox, Paul S. email , , , publications

My research program is centered on understanding fundamental aspects of cell division. During cell division, complex DNA-protein interactions transform diffuse interphase chromatin into discrete mitotic chromosomes, condensing them several thousand fold to facilitate spatial segregation of sister chromatids. Concomitantly, kinetochores form specifically at centromere regions of chromosomes and regulate force-producing interactions with microtubules. While these processes are absolutely required for genomic stability, the in vivo mechanisms of chromosome and kinetochore assembly remain unsolved problems in biology. I investigate 1) the spatiotemporal regulation of mitotic chromosome assembly, and 2) the molecular basis of centromere specification. To do so, I will combine biochemical approaches with high-resolution light microscopy of live cells, whole organisms, and in vitro systems.

Magness, Scott email , , , , publications

The primary focus of my research is to understand the genetic mechanisms underlying stem cell maintenance and differentiation with the goal of translating this information into therapeutic strategies. Using a Sox9EGFP mouse model and FACSorting we are able to specifically enrich for single multipotent intestinal epithelial stem cells that are able to generate mini-guts in a culture system. Our studies are now focused on manipulating, in vitro, the genetics of stem cell behavior through viral gene therapeutics and pharmacologic agents. Additionally, we are developing stem cell transplantation and tissue engineering strategies as therapies for inborn genetic disorders as well as damage and disease of the intestine. Using novel animal models and tissue microarrays from human colon cancers, we are investigating the role of Sox-factors in colorectal cancer.

Magnuson, Terry email , , , , , publications

The Magnuson Lab works in three areas – (i) Novel approaches to allelic series of genomic modifications in mammals, (ii)Mammalian polycomb-group complexes and development, (iii) Mammalian Swi/Snf chromatin remodeling complexes

Maness, Patricia F. email , , , publications

My research focuses on molecular mechanisms of mammalian nervous system development. We investigate mechanisms by which developing neurons migrate to the neocortex and form connections.

Martinez, Jennifer email , , , , , publications

The focus of the work in the Martinez lab is to examine the non-canonical roles for the autophagy machinery during inflammation.  Our recent work about LC3-associated phagocytosis (LAP) higlights the importance of this non-canonical autophagic process in maintaining tolerance and preventing unwanted autoinflammatory pathologies.

Matera, Greg email , , , , , , , publications

Research in our laboratory is focused on RNA. We aim to understand how ribonucleoprotein particles (snRNPs, mRNPs, etc.) are transcribed, packaged and transported to their final destinations in the cell.  We are also interested in the genetic and epigenetic forces that direct formation of microscopically visible subcellular structures (e.g. nuclear bodies). We use a combination of approaches, including Drosophila genetics, molecular cell biology, biochemistry, digital imaging microscopy and genome-wide analyses. Projects in the lab are focused on two areas:  models of a neurogenetic disease called Spinal Muscular Atrophy (SMA) and the functional analysis of post-translational modifications of chromatin and RNA-binding proteins important in cancer and other diseases.

Meeker, Rick email , , , , publications

Dr. Meeker’s research is focused on the mechanisms of HIV neuropathogenesis and the development of therapeutic strategies for the treatment of neuroinflammation. Inflammatory changes within the brain caused by the viral infection initiate a toxic cascade that disrupts normal neural function and can eventually lead to neuronal death. To explore the mechanisms responsible for this damage, we investigate changes in calcium homeostasis, glutamate receptor function and inflammatory responses in primary neuronal, microglial and macrophage cultures. New therapeutic approaches targeted to signal transduction pathways and calcium regulation that protect the neurons and reduce inflammation are under investigation.

Miao, Edward A email , , , publications

We study the mechanisms by which innate immunity detects virulence factor activity in pathogenic bacteria. Research focuses on how macrophages detect bacterial type III secretion systems through the inflammasome, which activates Caspase-1, promoting secretion of the cytokines IL-1b and IL-18, as well as pyroptotic cell death. We manipulate bacterial virulence genetically and probe how this alters innate immune detection during infection. This focus joins the fields of microbial pathogenesis and immunology, utilizing the knowledge and tools of both disciplines.

Moorman, Nat email , , , , publications

How does a virus gain control over the host cell? My laboratory is interested in answering this question at the molecular level. By combining molecular biology and virology with new technologies (e.g. mass spectrometry, next generation sequencing), we investigate the mechanisms utilized by viruses to hijack infected cells. By understanding the specific function(s) of viral proteins during infection, we identify strategies used by viruses for deregulation of host cell processes. We use this information to characterize novel features of cell signaling pathways during infection, and to identify potential targets for anti-viral therapeutics.

Morrow, Leslie email , , , , , , publications

Function, expression and trafficking GABA-A receptors in the CNS; effects of chronic ethanol exposure that leads to ethanol tolerance and dependence; role of endogenous neurosteroids on ethanol action and ethanol-induced adaptations. Role of neuroactive steroids in neuropsychiatric disease, including addiction, depressive disorders, anxiety disorders, inflammatory disorders.

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.

Nimchuk, Zachary email , , , , , , publications

Understanding how cells communicate and co-ordinate during development is a universal question in biology. My lab studies the cell to cell signaling systems that control plant stem cell production.  Plants contain discrete populations of self-renewing stem cells that give rise to the diverse differentiated cell types found throughout the plant.  Stem cell function is therefore ultimately responsible for the aesthetic and economic benefits plants provide us. Stem cell maintenance is controlled by overlapping receptor kinases that sense peptide ligands. Receptor kinase pathways also integrate with hormone signaling in a complex manner to modulate stem cell function.  My lab uses multiple approaches to dissect these networks including; genetics, genomics, CRISPR/Cas9 genome editing, live tissue imaging, and cell biological and biochemical methods.  This integrated approach allows us to gain an understanding of the different levels at which regulatory networks act and how they contribute to changes in form and function during evolution.

O’Brien, Lori email , , , , publications

Modern technologies from next-gen sequencing to high resolution imaging have advanced our knowledge of kidney development, function, and disease. We are among the pioneers utilizing techniques such as ChIP-seq, RNA-seq, modern genome editing, and imaging to understand how regulatory programs control progenitor populations during kidney development. Our goal is to understand how these programs contribute to progenitor specification and maintenance, and how they are altered during disease and aging. Our ultimate goal is translational applications of our research to develop new therapeutics and regenerative strategies.

Ostrowski, Lawrence E email , , , publications

The overall focus of research in my laboratory is to improve the diagnosis and treatment of airway diseases, especially those that result from impaired mucociliary clearance. In particular, our efforts focus on the diseases cystic fibrosis and primary ciliary dyskinesia, two diseases caused by genetic mutations that impair mucociliary clearance and lead to recurrent lung infections. The work in our laboratory ranges from basic studies of ciliated cells and the proteins that make up the complex structure of the motile cilia, to translational studies of new drugs and gene therapy vectors. We use a number of model systems, including traditional and inducible animal models, in vitro culture of differentiated mouse and human airway epithelial cells, and direct studies of human tissues. We also use a wide range of experimental techniques, from studies of RNA expression and proteomics to measuring ciliary activity in cultured cells and whole animals.

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.

Peifer, Mark email , , , , , , , publications

Cell adhesion, signal transduction, and cytoskeletal regulation during embryogenesis and in cancer.  We focus on the regulation of cadherin-based cell-cell adhesion, and on Wnt signaling and its regulation by the tumor suppressor APC.

Pylayeva-Gupta, Yuliya email , , , , publications

The goal of my research is to define molecular mechanisms of immune cell co-option by cancer cells, with the hope of identifying novel targets for immune cell reprogramming. Central to our approach is analysis immune cell subtypes in KRas-driven models of pancreatic cancer. We use cell and animals models to study signals important for pro-tumorigenic activity of immune cells, as well as define role of physiologically relevant oncogenic mutations in driving these signals and enabling immune escape.

Qian, Li email , , , , , publications

Our laboratory is interested in developing innovative approaches to regenerate or repair an injured heart. Our goal is to understand the molecular basis of cardiomyocyte specification and maturation and apply this knowledge to improve efficiency and clinical applicability of cellular reprogramming in heart disease. To achieve these goals, we utilize in vivo modeling of cardiac disease in the mouse, including myocardial infarction (MI), cardiac hypertrophy, chronic heart failure and congenital heart disease (CHD). In addition, we take advantage of traditional mouse genetics, cell and molecular biology, biochemistry and newly developed reprogramming technologies (iPSC and iCM) to investigate the fundamental events underlying the progression of various cardiovascular diseases as well as to discover the basic mechanisms of cell reprogramming.

Randell, Scott email , , , , , , , publications

Identification of airway epithelial stem cells; innate immunity in the airway; the pathophysiology of post-lung transplant ischemia reperfusion injury and bronchiolitis obliterans syndrome.

Reid, Lola email , , , publications

Two dynamically interacting sets of mechanisms govern tissue-specific gene expression and cell growth. 1) mechanisms in lineage biology regulate stem cells and their descendents, processes that define the repertoire of genes available to be regulated and 2) signal transduction mechanisms, induced by the synergistic effects of extracellular matrix components and soluble signals (hormones, growth factors), regulate the expression of the available genes. Studies in the lab focus on both classes of mechanisms in normal versus neoplastic tissue.

Reissner, Kathryn email , , , , publications

Research in our lab is focused on understanding how cocaine abuse affects glial cell physiology, in particular neuron-astrocyte communication.  We utilize the rat cocaine self-administration/reinstatement model, which allows us to test hypotheses regarding not only how chronic cocaine use affects properties of astrocytes and the tripartite synapse, but also how compounds affecting glial cells may influence synaptic processing within the brain’s reward neurocircuitry and behavioral measures of drug seeking.

Riordan, John email , , publications

The primary research focus is the structure, function and biosynthetic processing of membrane proteins which provide permeability pathways through the membranes of cells. Much of the current work is concentrated on the ion channel protein, CFTR (cystic fibrosis transmembrane conductance regulator) which is absent or dysfunctional in patients with cystic fibrosis. To elucidate the molecular mechanisms of CFTR function, we study single channel properties by electrophysiological techniques, enzymatic activity and physical interaction with other cellular molecules. A major objective of studies with the purified molecule is to obtain 3-dimensional structure information so that small molecules capable of recognizing features of its surface shape can be synthesized and used to modulate its folding and activity.

Rogers, Steve email , , , , , , publications

The research in our lab is centered on understanding the mechanisms and principles of movement at the cellular level. Cytoskeletal filaments – composed of actin and microtubules – serve as a structural scaffolding that gives cells the ability to divide, crawl, and change their shape.  Our lab uses a combination of cell biological, biochemical, functional genomic, and  high resolution imaging techniques to study cytoskeletal dynamics and how they contribute to cellular motion.

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.

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.

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.

Su, Lishan email , , , , , , , publications

Major areas of research: 1) HIV-1 Virology, Immuno-Pathology and Immuno-Therapy, 2) HBV Virology, Immuno-Pathology and Immuno-Therapy, 3) Novel Immune Therapeutics Including Adjuvants and Vaccines, and 4) Humanized Mouse Models of Human Liver and Immune System.  My laboratory studies both virology and immunology of HIV-1 and HBV persistent infection.  We focus on defining viral factors that counteract host innate anti-viral immunity.  We have also developed humanized mouse models to study human immuno-pathology of chronic HIV-1 and HBV infection in vivo.  We investigate how human immune cells are dysregulated and contribute to diseases during HIV-1 and HBV persistent infection.  We are currently focused on the HIV-1/pDC/IFN-I axis that plays a critical role in HIV-1 persistence and AIDS, and on the HBV/Macrophage interaction in liver diseases.  In addition, we are developing novel immune modulatory therapeutics including antibodies, adjuvants and vaccines.

Tarran, Robert email , , publications

A critical component of airways innate defense is the thin liquid layer lining airway surfaces, the periciliary liquid (PCL), that provides a low viscosity solution for ciliary beating and acts a lubricant layer for mucus transport. Normal airways appear to be able to sense the PCL volume and adjust ion channel activity accordingly.  The long term goal of this laboratory is to understand how homeostasis of PCL volume occurs in airway epithelia under normal and pathophysiological conditions. Currently, research in the Tarran lab is focused on three main areas: 1) Regulation of epithelial cell function by the extracellular environment, 2) Gender differences in cystic fibrosis lung disease and 3) The effects of cigarette smoke on epithelial airway ion transport.  We utilize cell biological and biochemical techniques coupled with in vivo translational approaches to address these questions.

Taylor, Anne Marion email , , publications

Local mRNA translation is critical for axon regeneration, synapse formation, and synaptic plasticity. While much of research has focused on local translation in dendrites and in peripheral axons, less is known about local translation in smaller diameter central axons due to the technical difficulty of accessing them. We developed microfluidic technology to allow access to axons, as well as nascent boutons and fully functional boutons. We identified multiple transcripts that are targeted to cortical and hippocampal axons in rat (Taylor et al. J Neurosci 2009). Importantly, this work countered the prevailing view that local mRNA translation does not occur in mature axons. We are actively investigating transcripts in axons that may play a role in establishing proper synaptic connections. We are also using our technology to identify transcripts targeted to axons and boutons in human neurons. These studies are a critical step towards the identification of key genes and signaling molecules during synapse development, axonal regeneration, and proper circuit function.

Thompson, Nancy email , , publications

The immune system is a network of interacting biological cells. The molecular events that lead to the activation and regulation of these cells often occur at the cell surface. However, little is known about the arrangement, motions and interactions of the participating cell-surface molecules. To examine these phenomena, we construct model cell membranes on planar supports from purified or synthesized molecules.  Recently developed techniques in laser-based fluorescence microscopy can then be employed to examine the behavior of select fluorescently labeled molecules at or near the supported planar membranes.  This research is significant not only in the basic understanding of the immune system, but also in other areas of cell-cell communication and cell membrane biophysics, in the physics of two-dimensional fluids, and in biotechnology.

Ting, Jenny email , , , , , , , , , , publications

Topics include gene discovery, genomics/proteomics, gene transcription, signal transduction, molecular immunology.  Disease relevant issues include infectious diseases, autoimmune and demyelinating disorders, cancer chemotherapy, gene linkage.

Vaziri, Cyrus email , , , , , , publications

Our broad long-term goal is to understand how mammalian cells maintain ordered control of DNA replication during normal passage through an unperturbed cell cycle, and in response to genotoxins (DNA-damaging agents).  DNA synthesis is a fundamental process for normal growth and development and accurate replication of DNA is crucial for maintenance of genomic stability.  Many cancers display defects in regulation of DNA synthesis and it is important to understand the molecular basis for aberrant DNA replication in tumors.  Moreover, since many chemotherapies specifically target cells in S-phase, a more detailed understanding of DNA replication could allow the rational design of novel cancer therapeutics.  Our lab focuses on three main aspects of DNA replication control:  (1) The S-phase checkpoint, (2) Trans-Lesion Synthesis (TLS) and (3) Re-replication.

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.

Williams, Carmen J. email , , , , publications

Reproductive biology of early mammalian embryogenesis including gametogenesis, fertilization, and preimplantation embryo development. Effects of environmental disrupting chemicals on female reproductive tract development and function, with a focus on epigenetic alterations.

Williams, Scott E. email , , , , , , , , publications

Divisions and decisions in development and disease. The mammalian skin epithelium is an ideal model system to study fundamental questions in stem cell and cancer biology. It is accessible; it can be cultured, genetically manipulated and transplanted; and its resident stem cells possess unparalleled regenerative capacity. Our skin, unlike many other organs, undergoes continuous growth and turnover. In development and homeostasis, progenitors in the skin must balance self-renewal and differentiation programs. We have found that asymmetric cell divisions are a critical mechanism by which skin progenitors maintain this equilibrium. We are interested in studying how this asymmetry is controlled at a molecular level, and how division orientation impacts cell fate choices in normal and neoplastic growth. To facilitate these and other studies in diverse epithelia, we have developed a powerful functional tool, lentiviral in vivo RNAi, which allows us to rapidly perform functional studies on any gene in the intact mouse in weeks instead of years. Our broad goal will be to use this technique, in combinations of candidate and screening approaches, to dissect pathways that influence stem cell differentiation. I will be joining the Pathology Department in April, 2013 and am seeking passionate, open-minded, and interactive students for the summer and beyond.

Wright, J. Timothy email , , , , publications

The Wright laboratory research is focused primarily on defining the phenotype and genotype relationships in a variety of craniofacial conditions such as amelogenesis and dentinogenesis imperfecta, ectodermal dysplasias, and the tricho-dento-osseous syndrome.  This is accomplished through a combination of human gene discovery approaches, the use of transgenic mice, and cell culture systems to explore mechanisms that explain genotype-phenotype relationships.  His most recent research includes investigation of the molecular controls of tooth formation as well as gene expression in tumorigenesis involving  odontogenic tumors such as ameloblastomas and keratocystic odontogenic tumors.

Xiong, Yue email , , , , , publications

Using genetic, cell biology, biochemical and proteomic approaches to determine the function and mechanism of – (1) CDK inhibitors in development and tumor suppression, (2) the p53 degradation and transport, and (3) RING family of ubiquitin ligases.

Yeh, Elaine email , , , publications

The site of microtubule attachment to the chromosome is the kinetochore, a complex of over 60 proteins assembled at a specific site on the chromosome, the centromere. Almost every kinetochore protein identified in yeast is conserved through humans and the organization of the kinetochore in yeast may serve as the fundamental unit of attachment. More recently we have become interested in the role of two different classes of ATP binding proteins, cohesions (Smc3, Scc1) and chromatin remodeling factors (Cac1, Hir1, Rdh54) in the structural organization of the kinetochore and their contribution to the fidelity of chromosome segregation.

Zhang, Yanping email , , , , , publications

We employ modern technologies – genomics, proteomics, mouse models, multi-color digital imaging, etc. to study cancer mechanisms. We have made major contributions to our understanding of the tumor suppressor ARF and p53 and the oncoprotein Mdm2.

Zylka, Mark J. email , , , , , , , publications

Our research is focused on two general areas:  1. Autism and 2. Pain.  Our autism research is focused on topoisomerases and other transcriptional regulators that were recently linked to autism.  We use genome-wide approaches to better understand how these transcriptional regulators affect gene expression in developing and adult neurons (such as RNA-seq, ChIP-seq, Crispr/Cas9 for knocking out genes).  We also assess how synaptic function is affected, using calcium imaging and electrophysiology.   In addition, we are performing a large RNA-seq screen to identify chemicals and drugs that increase risk for autism.   /  / Our pain research is focused on lipid kinases that regulate pain signaling and sensitization.  This includes work with cultured dorsal root ganglia (DRG) neurons, molecular biology and behavioral models of chronic pain.  We also are working on drug discovery projects, with an eye towards developing new therapeutics for chronic pain.