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[ PhD Program: Cell Signaling Keyword: ]

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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.

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.

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.

Breese, George email , , , , , publications

This multidisciplinary laboratory has 6 interests: 1) Defining regionally specific adaptations responsible for functions altered by chronic ethanol;  2) Characterizing regional CNS biochemical changes induced by stress and CRF after chronic ethanol;  3) Defining the role of central cytokines in behaviors induced by stress; 4) Exploring how a benzodiazepine (BZD) agonist shares actions with a BZD antagonist;  5) Defining TRH receptor subtype(s) responsible for its anti-anxiety and analeptic actions;  and  6) Defining the action of galanin on ethanol withdrawal-induced anxiety.  To undertake our interests, behavioral, anatomical, pharmacological, electrophysiological, biochemical, and molecular biological approaches are used.

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.

Burks, Wesley email , , , , publications

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

Campbell, Sharon email , , , , publications

Current research projects in the Campbell laboratory include structural, biophysical and biochemical studies of wild type and variant Ras and Rho family GTPase proteins, as well as the identification, characterization and structural elucidation of factors that act on these GTPases.  Ras and Rho proteins are members of a large superfamily of related guanine nucleotide binding proteins.  They are key regulators of signal transduction pathways that control cell growth. Rho GTPases regulate signaling pathways that also modulate cell morphology and actin cytoskeletal organization.  Mutated Ras proteins are found in 30% of human cancers and promote uncontrolled cell growth, invasion, and metastasis. Another focus of the lab is in biochemical and biophysical characterization of the cell adhesion proteins, focal adhesion kinase, vinculin, paxillin and palladin.  These proteins are involved in actin cytoskeletal rearrangements and cell motility, amongst other functions. Most of our studies are conducted in collaboration with laboratories that focus on molecular and cellular biological aspects of these problems. This allows us to direct cell-based signaling, motility and transformation analyses. Member of the Molecular & Cellular Biophysics Training Program.

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.

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.

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?

Crews, Fulton email , , , , , publications

Research in the laboratory focuses on mechanisms of neurodegeneration and regeneration, particularly stem cells in brain.

Damania, Blossom email , , , , , publications

The work in our laboratory is focused on understanding the molecular pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic human virus. KSHV is associated with several types of cancer in the human population. We study the effect of KSHV viral proteins on cell proliferation, transformation, apoptosis, angiogenesis and cell signal transduction pathways. We also study viral transcription factors, viral replication, and the interactions of KSHV with the human innate immune system. Additionally, we are developing drug therapies that curb viral replication and target tumor cells.

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.

Dohlman, Henrik email , , , , , , publications

We use an integrated approach (genomics, proteomics, computational biology) to study the molecular mechanisms of hormone and drug desensitization. Our current focus is on RGS proteins (regulators of G protein signaling) and post-translational modifications including ubiquitination and phosphorylation.

Duncan, Alex email , , , , publications

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

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.

Fessler, Michael B. email , , , publications

Fessler laboratory investigates mechanisms of the innate immune response, in particular Toll like Receptor (TLR) pathways and how they regulate inflammatory and host defense responses in the lung.  To this end, we use both in vitro (macrophage cultures) and in vivo (mouse models of acute lung injury and pneumonia) model systems, and also use translational approaches (e.g., studies using human peripheral blood leukocytes and alveolar macrophages).  An area of particular interest within the laboratory is defining how cholesterol trafficking and dyslipidemia innate immunity.

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.

Gomez, Shawn email , , , , publications

Our primary research is in the area of computational systems biology, with particular interest in the study of biological signaling networks; trying to understand their structure, evolution and dynamics. In collaboration with wet lab experimentalists, we develop and apply computational models, including probabilistic graphical and multivariate methods along with more traditional engineering approaches such as system identification and control theory, to current challenges in molecular biology and medicine. Examples of recent research projects include: prediction of protein interaction networks, multivariate modeling of signal transduction networks, and development of methods for integrating large-scale genomic data sets.

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.

Harden, Kendall email , , , , , publications

We focus on mechanistic/structural aspects of regulatory proteins (heterotrimeric and Ras family GTPases, RGS proteins, and PLC isozymes) involved in inositol lipid signaling, and on G protein-coupled receptors for extracellular nucleotides.

Hursting, Stephen D email , , , , publications

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

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.

Kieber, Joe email , , , , , publications

Hormones influence virtually every aspect of plant growth and development. My lab is examining the molecular mechanisms controlling the biosynthesis and signal transduction of the phytohormones cytokinin and ethylene, and the roles that these hormones play in various aspects of development. We employ genetic, molecular, biochemical, and genomic approaches using the model species Arabidopsis to elucidate these pathways.

Kodavanti, Urmila P email , , , , publications

Our research focuses on understanding mechanisms of cardiovascular and metabolic health effects of inhaled air pollutants. Specific emphasis is given to susceptibility variations due to underlying cardiovascular disease, obesity, and diabetes. The roles of genetic versus physiological factors are examined. We use molecular and high throughput genomics, and proteomics techniques to establish a link with disease phenotype and physiological alterations. State-of-the-art EPA inhalation facilities are used for air pollution exposures in animal models with or without genetic predisposition. The role of environment in disease burden is the focus.

Krupenko, Natalia email , , , , , publications

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

Krupenko, Sergey email , , , , publications

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

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.

LeCluyse, Edward L email , , , , publications

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

Lentz, Barry email , , , , publications

The regulatory role of platelet membrane phosphatidylserine in blood coagulation; mechanism of protein-mediated membrane fusion in secretory processes and virus infection.  Director of the Molecular & Cellular Biophysics Training Program.

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, Rihe email , , , , publications

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

Liu, Zhi email , , , , publications

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

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.

Mackman, Nigel email , , , , publications

The major focus of Mackman lab is the procoagulant protein tissue factor. This is the primary cellular initiator of blood coagulation. We study its role in hemostasis, thrombosis, inflammation, ischemia-reperfusion injury and tumor growth.  LPS induction of the tissue factor gene in human monocytic cells and endothelial cells is mediated by various transcription factors, such as AP-1, NF-ĸB and Egr-1. More recently, we found that the phosphatidylinositol-3-kinase protein kinase B intracellular signaling pathway suppresses LPS activation of monocytes and endothelial cells.  We found that inhibition of either tissue factor or the downstream coagulation protease thrombin reduced infarct size in a rabbit model of cardiac ischemia-reperfusion injury. We showed that the tissue factor-thrombin pathway increased inflammation during myocardial ischemia-reperfusion injury by inducing chemokine expression and enhancing the recruitment of neutrophils. We have generated a number of mouse models expressing different levels of both mouse and human tissue factor. These mice have been used to provide new insights into the role of tissue factor in hemostasis and thrombosis. In 2007, we developed a new assay to measure levels of microparticle tissue factor in plasma. We found that elevated levels of microparticle tissue factor are associated with venous thromboembolism in cancer patients.

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

Markovic-Plese, Silva email , , , , , publications

My long-term goal is to understand and therapeutically target the key mechanisms of disease development in patients with multiple sclerosis (MS).  Our research has been focused on the molecular events involved in the initiation of the autoimmune response in MS, and on the mechanisms of action of immunomodulatory therapies for this disabling disease.  Current projects in the laboratory include transcriptional and proteomic profiling of the peripheral blood cells and cerebrospinal fluid obtained from patients in the early phase of the disease, which lead to the discovery of the high levels of IL-11 in the CSF and its high up-regulation in the blood-derived CD4+ T-cells in patients with clinically isolated syndrome (CIS) suggestive of MS. Our center is uniquely positioned to perform the proposed research, having an access to the clinical samples through the integrated clinical and cellular/molecular biology research.

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.

Matsushima, Glenn K email , , , , , , publications

Our laboratory is interested in innate immune responses during injury to the central nervous system and during inflammation during microbial infections.  Our laboratory has a special interest in autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus.  We also are pursuing drug discovery projects targeting receptors that may modulate demyelinating disease and immune responses.  We use molecular, cellular and biochemical approaches both in vitro and in vivo to identify the function of key mediators during pathogenesis.

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.

Moody, Cary email , , , , publications

The work in my laboratory focuses on the molecular biology of human papillomaviruses (HPV), small DNA viruses that exhibit epithelial tropism. Certain types of HPV are considered the causative agents of cervical cancer and are also associated with cancers of the anus, oropharynx and esophagus.  My lab is interested in defining mechanisms that regulate the productive phase of the HPV life cycle, which is restricted to differentiating epithelia and includes viral genome amplification, late gene expression and virion production. Using various methods of epithelial differentiation, we are studying how HPV proteins modulate cell signaling pathways, including the DNA damage response and apoptosis, to facilitate viral replication, which in turn contributes to viral pathogenesis and possibly transformation. I will be accepting rotation students beginning in the winter of 2010.

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.

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.

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.

Purvis, Jeremy email , , , , , publications

We study the behavior of individual cells with a specific focus on “irreversible” cell fate decisions such as apoptosis, senescence, and differentiation. Why do genetically identical cells choose different fates? How much are these decisions controlled by the cell itself and how much is influenced by its environment? We address these questions using a variety of experimental and computational approaches including time-lapse microscopy, single-molecule imaging, computational modeling, and machine learning. Our ultimate goal is to not only understand how cells make decisions under physiological conditions—but to discover how to manipulate these decisions to treat disease.

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.

Reed, Jason email , , , , , publications

Regulation of plant development:  We use techniques of genetics, molecular biology, microscopy, physiology, and biochemistry to study how endogenous developmental programs and exogenous signals cooperate to determine plant form.  The model plant Arabidopsis thaliana has numerous technical advantages that allow rapid experimental progress.  We focus on how the plant hormone auxin acts in several different developmental contexts.  Among questions of current interest are i) how auxin regulates patterning in embryos and ovules, ii) how light modifies auxin response, iii) how feedback loops affect kinetics or patterning of auxin response, iv) how flower opening and pollination are regulated, and v) whether natural variation in flower development affects rates of self-pollination vs. outcrossing.

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.

Shank, Elizabeth email , , , , , , publications

My laboratory studies chemically mediated interactions between microbes, particularly those that lead to alterations in bacterial development. In the natural world, interspecies chemical communication contributes to the stability and function of complex microbial communities. We explore the mechanisms and molecules that microbes use to influence their microbial neighbors both in the laboratory and in natural environments using genetics, microscopy, chemical imaging, and next generation sequencing. Our goal is to gain insights into microbial ecology, identify compounds with novel bioactivities, and obtain chemical tools to manipulate bacterial behavior to our benefit.

Sondek, John email , , , , , , publications

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

Tamayo, Rita email , , , , publications

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

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.

Tisch, Roland email , , , publications

Projects involve the study of cellular and molecular events involved in autoimmunity, and development and application of genetic vaccines to prevent and treat autoimmunity and cancer.

Tong, Haiyan email , , , , publications

Research in my laboratory focuses on the cardiovascular effects of air pollution and other environmental pollutants in human, animal, and in vitro models, as well as the dietary interventional strategies to mitigate the adverse health effects of air pollution exposure. We are currently conducting two clinical studies to investigate the cardiopulmonary effects of air pollution exposure, and to determine whether dietary omega-3 fatty acids can mitigate the air pollution-induced health effects in human volunteers. These studies provide good training opportunities for students who are interested in training in clinical and translational toxicology research.

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.

Vilen, Barbara email , , , , , publications

We are interested in understanding how autoreactive B cells become re-activated to secrete autoantibodies that lead to autoimmune disease.  Our research is focused on understanding how signal transduction through the B cell antigen receptor (BCR) and Toll Like Receptors (TLR) lead to secretion of autoantibodies in Systemic Lupus Erythematosus (SLE).

Wan, Yisong email , , , , publications

We are a molecular genetics laboratory studying immune functions by using mouse models. The focus of our research is to investigate the molecular mechanisms of immune responses under normal and pathological conditions. Our goal is to find therapies for various human immune disorders, such as autoimmunity (type 1 diabetes and multiple sclerosis), tumor and cancer, and inflammatory diseases (inflammatory bowel disease, asthma and arthritis).

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.

Whang, Young E. email , , , , publications

My laboratory is interested in characterizing the role of cytoplasmic signal transduction pathways in regulation of androgen receptor activity and progression of prostate cancer.  Our studies have focused on HER-2 receptor tyrosine kinase and we have demonstrated that HER-2 activation stimulates androgen receptor activity and HER-2 inhibition inhibits androgen receptor transcriptional function at the level of recruitment to the androgen responsive enhancers.  These findings have led to the design and initiation of the protocol involving lapatinib, a clinical HER-2 inhibitor, in treatment of patients with prostate cancer.  More recently, we have demonstrated that activated Cdc42-associated kinase Ack1 promotes progression of prostate cancer via tyrosine phosphorylation of androgen receptor at Tyr-267 and Tyr-363 residues.  We are interested in further characterizing the role of tyrosine phosphorylation of androgen receptor in prostate cancer and development of Ack1 targeted therapy for clinical use.

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.

Wilson, Elizabeth M email , , , , , publications

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

Wolfgang, Matthew C. email , , , , , publications

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen responsible for a variety of diseases in individuals with compromised immune function. Dr. Wolfgang’s research focuses on the pathogenesis of Pseudomonas aeruginosa infection.  The goal of his research is to understand how this opportunistic pathogen coordinates the expression of virulence factors in response to the host environment. Projects in his laboratory focus on the regulation of intracellular cyclic AMP, a second messenger signaling molecule that regulates P. aeruginosa virulence. Dr. Wolfgang’s laboratory uses a combination of molecular genetics and biochemical approaches to understand how P. aeruginosa controls the synthesis, degradation and transport of cAMP in response to extracellular cues. Other related projects focus on the regulation and function of P. aeruginosa Type IV pili (TFP). TFP are cAMP regulated surface organelles that are critical for bacterial colonization of human mucosal tissue. In addition, the Wolfgang lab is actively involved in characterizing the lung microbiome of patients with chronic airway diseases and studying the interactions between P. aeruginosa and other bacterial species during mixed infections.

Zhang, Qing email , , , , , publications

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

Zhang, Qisheng email , , , , publications

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