Faculty Database:
[ Phd Program: Cell Biology & Physiology ]

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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.

Caron, Kathleen email , , , , , publications

Gene targeting and state-of-the-art phenotyping methods are used to elucidate the reproductive and cardiovascular roles of the adrenomedullin system and to characterize the novel GPCR-signaling mechanism of Adm’s receptor and RAMP’s.

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.

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.

Conlon, Frank email , , , , , , publications

Our lab is studying the molecular mechanisms which are involved in the induction and proliferation and patterning of cardiac progenitor cell populations. To identify the molecular pathways involved in these processes, we have used Xenopus and mouse as model systems with particular focus on the endogenous role of genes implicated in the early steps of cardiogenesis and human congenital heart disease. Present projects in the lab involve embryological manipulations, tissue explant cultures, molecular screens as well as protein-DNA interaction experiments, biochemistry and promoter analysis.

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

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

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.

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.

Diering, Graham email , , , , publications

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.

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.

Faber, James E. email , , , , publications

We study mechanisms of formation of the collateral circulation in embryonic and neonatal mice, 2) collateral growth and angiogenesis in models of ischemic disease in adult mice, 3) signaling in collateral endothelial cells, and 4) the genetic and environmental basis for the large variation in collateral vessel formation in the embryo and growth in ischemic disease (see Faber et al Physiol Genom 2007; Circ Res 2008) using genome-wide mapping and expression profiling (QTL, eQTL), consomic and haplotype analyses, plus physiologic, cellular and molecular study of candidate genes. Techniques in addition to those mentioned above include physiologic analysis of mouse models of cerebral, coronary and hindlimb ischemic disease, vascular imaging (angiography, laser Doppler flowmetry, micro-computed tomography), signaling analysis, cell and molecular biology.  We also study adaptive and pathological arterial wall growth and remodeling in the adult. The laboratory collaborates with other groups at UNC and other institutions in the US and elsewhere, providing varied opportunities for professional development.

Frohlich, Flavio email , , , , , , publications

Our goal is to revolutionize the treatment of psychiatric and neurological illness by developing novel brain stimulation paradigms. We identify and target network dynamics of physiological and pathological brain function. We combine computational modeling, optogenetics, in vitro and in vivo electrophysiology in animal models and humans, control engineering, and clinical trials. We strive to make our laboratory a productive, collaborative, and happy workplace.

Gershon, Timothy R email , , , , publications

As a pediatric neurologist and brain tumor researcher, I seek to understand the link between brain growth and childhood brain tumors.  During postnatal cerebellar development, neural progenitors divide rapidly.  This wave of neurogenesis must be strictly controlled to prevent formation of medulloblastoma, a malignant neuroblastic tumor of the cerebellum.  Using transgenic mice that express constitutively active Smoothened, we are able to recapitulate tumorigenesis in mice.  These tumor-prone mice develop medulloblastomas that model the human tumor in pathology and gene expression.  We use this primary brain tumor model to gain novel insight into medulloblastoma pathogenesis and treatment.

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.

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.

Hige, Toshi email , , , , , publications

[MOVING TO UNC-CH IN JANUARY 2018] Flexibility of the brain allows the same sensory cue to have very different meaning to the animal depending on past experience (i.e. learning and memory) or current context. Our goal is to understand this process at the levels of synaptic plasticity, neural circuit and behavior. Our model system is a simple brain of the fruit fly, Drosophila. We employ in vivo electrophysiology and two-photon calcium imaging together with genetic circuit manipulation. Taking advantage of this unique combination, we aim to find important circuit principles that are shared with vertebrate systems.

 

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.

Kash, Thomas email , , , , , , publications

Emotional behavior is regulated by a host of chemicals, including neurotransmitters and neuromodulators, acting on specific circuits within the brain. There is strong evidence for the existence of both endogenous stress and anti-stress systems. Chronic exposure to drugs of abuse and stress are hypothesized to modulate the relative balance of activity of these systems within key circuitry in the brain leading to dysregulated emotional behavior. One of the primary focuses of the Kash lab is to understand how chronic drugs of abuse and stress alter neuronal function, focusing on these stress and anti-stress systems in brain circuitry important for anxiety-like behavior. In particular, we are interested in defining alterations in synaptic function, modulation and plasticity using a combination of whole-cell patch-clamp physiology, biochemistry and mouse models.  Current projects are focused on the role of a unique population of dopamine neurons in alcoholism and anxiety.

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.

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.

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.

Mack, Christopher P. email , , , , , publications

My research goals are to identify the mechanisms by which environmental factors regulate smooth muscle cell phenotype and to define the transcriptional pathways that regulate SMC-specific gene expression.

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.

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.

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

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

Makowski, Liza email , , , , , , publications

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

Manis, Paul B. email , , , , publications

We are interested in the cellular and network mechanisms of sensory information processing in the central nervous system, with an emphasis on the neural substrates for hearing. We study functional network organization, synaptic function, the roles of ion channels and cellular excitability, and short and long-term synaptic plasticity, in the auditory brainstem and auditory cortex.  Experimentally, we use patch clamp methods in brain slices, optogenetics and laser scanning photostimulation, multiphoton imaging, and computational neuroscience (modeling), in normal and transgenic mouse models. The lab also has collaborative projects related to schizophrenia (prefrontal cortex; Dr. Patricia Maness, UNC) and connectomics (cochlear nucleus and MNTB; Dr. George Spirou, WVU).

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.

McCullough, Shaun D. email , , , , , publications

Dr. McCullough’s lab focuses around the role of the epigenetic elements as both a molecular mechanism mediating the effects of toxic exposures and as a biomarker for predicting susceptible populations and identifying factors that can be used to mitigate adverse health outcomes.  The lab employs a translational research approach to toxicology with an emphasis on molecular biology that uses both advanced in vitro primary cell models and in vivo clinical controlled human exposure studies.

McElligott, Zoe email , , , publications

Research in the McElligott lab focuses on the circuits and plasticity that underlie the development and manifestation of psychiatric illness, specifically disorders on the affective spectrum including alcohol use disorders, drug abuse and anxiety disorders. The lab has expertise in studying neurotransmission from the level of signaling in individual cells through behavior utilizing a variety of techniques including: whole-cell electrophysiology, in vivo and ex vivo fast-scan cyclic voltammetry (FSCV), circuit manipulations (optogenetics, chemogenetics, caspase ablation), and behavioral assays.  There are several ongoing projects in the lab. One area we are focused on explores the role of neurons in the central nucleus of the amygdala (CeA) that express the neuropeptide neurotensin and the role these neurons play in alcohol related phenotypes. Additionally we are interested in exploring how norepinephrine modulates neurotransmission within the brain and how the norepinephrine system itself is modulated in models of substance abuse and post-traumatic stress. Beyond these studies, we are actively engaged in several other collaborative projects with other labs at UNC, as well as around the world.

Neher, Saskia email , , , , , publications

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

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.

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.

Phanstiel, Doug email , , , , publications

It is estimated that less than 2% of the human genome codes for a functional protein.  Scattered throughout the rest of the genome are regulatory regions that can exert control over genes hundreds of thousands of base pairs away through the formation of DNA loops.  These loops regulate virtually all biological functions but play an especially critical role in cellular differentiation and human development. While this phenomenon has been known for thirty years or more, only a handful of such loops have been functionally characterized.  In our lab we use a combination of cutting edge genomics (in situ Hi-C, ATAC-seq, ChIP-seq), proteomics, genome editing (CRISPR/Cas), and bioinformatics to characterize and functionally interrogate dynamic DNA looping during monocyte differentiation.  We study this process both in both healthy cells and in the context of rheumatoid arthritis and our findings have broad implications for both cell biology as well as the diagnosis and treatment of human disease.

Philpot, Ben email , , , , publications

My lab is driven to understand the neuronal pathologies underlying neurodevelopmental disorders, and to use this information to identify novel therapeutics.  We focus our research on monogenic autism spectrum disorders, including Angelman, Rett, and Pitt-Hopkins syndromes.  We employ a diverse number of techniques including: electrophysiology, molecular biology, biochemistry, mouse engineering, and in vivo imaging.

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.

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.

Smith, Spencer L email , publications

My laboratory explores neural circuitry and how it changes moment-to-moment, and over a lifetime, using imaging, electrophysiology, and behavior. The goal of our research is a better understanding of how molecular, cellular, and synaptic mechanisms underlie the function of large-scale brain circuitry. Ultimately, we hope this better understanding may illuminate the mechanisms in complex diseases like autism and schizophrenia, and suggest new therapeutic strategies.

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.

Song, Juan email , , , , publications

Our primary research interest is to identify the mechanisms that regulate neural circuit organization and function at distinct stages of adult neurogenesis, and to understand how circuit-level information-processing properties are remodeled by the integration of new neurons into existing circuits and how disregulation of this process may contribute to various neurological and mental disorders. Our long-range goals are to translate general principles governing neural network function into directions relevant for understanding neurological and psychiatric diseases. We are addressing these questions using a combination of cutting-edge technologies and approaches, including optogenetics, high-resolution microscopy, in vitro and in vivo electrophysiology, genetic lineage tracing and molecular biology.

Stuber, Garret email , , , publications

My lab focuses on delineating the neural circuits that mediate motivated behavioral states that are disrupted in diseases such as addiction, schizophrenia, depression, eating disorder and autism spectrum disorders.  Using animal models we employ a range to cutting edge tools and techniques to study neural circuit function.  Advances in the newly emerging fields such as optogenetics and in vivo imaging have now given us unprecedented abilities to control and monitor the activity of genetically defined neural circuit elements in the behaving animal.  Our research will ultimately uncover how genetically defined cell types in the brain orchestrate and control complex motivated behavioral states.

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, Joan M. email , , , , , publications

The goal of our research is to identify signaling mechanisms that contribute to normal and pathophysiological cell growth in the cardiovascular system.  We study cardiac and vascular development as well as heart failure and atherosclerosis.

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.

Weinberg, Richard email , , , publications

I’m a neurobiologist who uses immunocytochemistry and electron microscopy to address functional questions. I am trying to elucidate the molecular organization of synaptic signaling in the rodent neocortex, hippocampus, and striatum. I’m also interested in the actin cytoskeleton of dendritic spines, and how spines may remodel during LTP.

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, 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.

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.