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In my lab, we are exploring the roles that kinases play in neurodegeneration through the creation of high-quality, small molecule tools. Our team designs, synthesizes, and evaluates small molecules capable of kinase modulation, sometimes targeting kinase inhibition and sometimes kinase activation. In order to accomplish our aims, we work closely with X-ray crystallographers within the larger SGC and with biologists, including experts in using stem cells to model neurodegenerative diseases. We seek enthusiastic students with an interest in neuroscience who are willing to learn and apply techniques that span chemistry and biology to better understand and address neurodegeneration.

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

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

How do networks of cells synchronize behaviors across differing spatial and temporal scales? This fundamental aspect of cellular dynamics is broadly relevant to understanding many biological systems in which the coherence of electrical or chemical signals is required for multicellular patterning or organ function. Our group’s primary research interests are related to understanding the cellular and microenvironmental conditions that are required to support the biorhythmic behavior of the system of cells that natively control heart rate, cardiac pacemaker cells. We utilize a variety of techniques including computational modeling, next generation sequencing, in vivo genetic manipulation, super-resolution imaging, and direct physiological recording to investigate the developmental processes that assemble the hearts pacemaking complex. The ultimate goals of these studies is to determine how the pacemaker cell lineage is patterned in the embryo, build strategies towards fabricating this cell type for therapeutic purposes, and identify vulnerabilities that may lead to pacemaker cell pathologies in humans.

The overall goal of our lab is to perform research that contributes to a better understanding of pancreatic cancer biology and leads to improved treatments for this disease. One major focus of our studies is the metabolic activity, autophagy, which is a self-degradation process whereby cells can orderly clear defective organelles and recycle macromolecules as a nutrient source. Current projects are focused on further advancing autophagy inhibition as an anti-RAS therapeutic approach, as well as delineating other metabolic consequences of RAF-MEK-ERK MAPK inhibition.

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

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

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.

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.

The overriding goal of Dr. Coleman’s work is to identify novel treatments for alcohol use disorders (AUD) and associated peripheral disease pathologies. Currently, this includes: the role of neuroimmune Signaling in AUD pathology, the role of alcohol-associated immune dysfunction in associated disease states, and novel molecular and subcellular mediators of immune dysfunction such as extracellular vesicles, and regenerative medicine approaches such as microglial repopulation.

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.

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?

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.

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.

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.

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.

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.

The Dominguez lab studies how gene expression is controlled by proteins that bind RNA. RNA binding proteins control the way RNAs are transcribed, spliced, polyadenylated, exported, degraded, and translated. Areas of research include: (1) Altered RNA-protein interactions in cancer; (2) RNA binding by noncanonical domains; and (3) Cell signaling and RNA processing.

Appropriate allocation of cellular lipid stores is paramount to maintaining organismal energy homeostasis. Dysregulation of these pathways can manifest in human metabolic syndromes, including cardiovascular disease, obesity, diabetes, and cancer. The goal of my lab is to elucidate the molecular mechanisms that govern the storage, metabolism, and intercellular transport of lipids; as well as understand how these circuits interface with other cellular homeostatic pathways (e.g., growth and aging). We utilize C. elegans as a model system to interrogate these evolutionarily conserved pathways, combining genetic approaches (forward and reverse genetic screens, CRISPR) with genomic methodologies (ChIP-Seq, mRNA-Seq, DNA-Seq) to identify new components and mechanisms of metabolic regulation.

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.

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.

My lab focuses on developing bioinspired molecular constructs and material platforms that can mimic proteins and be programmed to respond to stimuli resulting from biomolecular recognition. Major efforts are directed to design peptide- and nucleic acid-based scaffolds or injectable nanostructures to create artificial extracellular matrices that can directly signal cells.

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.

The Gladden lab studies how cell adhesion and cell polarity are intertwined in normal tissue development and how these pathways are altered in diseases such as cancer. We use a combination of 3D cell culture, mouse models and protein biochemistry to study how cell polarity and adhesion regulate tissue organization. Our work focuses on the interplay between cell adhesion and cell polarity proteins at the adherens junction and how these proteins regulate tissue organization. We concentrate on the development of the endometrium epithelium in the female reproductive tract and the cell biology of endometrial cancer.

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.

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

Dynamic control of signaling networks in living cells; Rho family and MAPK networks in motility and network plasticity; new tools to study protein activity in living cells (i.e., biosensors, protein photomanipulation, microscopy). Member of the Molecular & Cellular Biophysics Training Program and the Medicinal Chemistry Program.

Imagine a naturally intelligent therapy that can seek out and destroy cancer cells like no other available treatment.  In the Hingtgen Lab, we are harnessing Nobel Prize-winning advancements to create a new type of anti-cancer treatment: personalized stem cell-based therapies.  We use a patient’s own skin sample and morph it into cells that chase down and kill cancer. We take advantage of a little-known aspect of stem cells- they can home in on cancer by picking up a signal through receptors on the cell surface. All the while, the therapeutic stem cells are pumping out potent anti-cancer drugs that selectively kill any cancer cell nearby while leaving the healthy brain unharmed. Our initial studies focused on aggressive brain cancers, however we quickly expanded our testing to a variety of cancer types. Working at the interface of basic science and human patient testing, our ultimate goal is to translate this novel approach into the clinical setting where it can re-define treatment for cancers that currently have no effective treatment options.

Our preclinical research is based on the concept that drugs of abuse gain control over behavior by hijacking molecular mechanisms of neuroplasticity within brain reward circuits. Our lab focuses on three main research questions: (1) Discover the neural circuits and molecular mechanisms that mediate the reinforcing and pleasurable subjective effects of alcohol and other drugs, (2) Identify the long-term effects of cocaine and alcohol abuse during adolescence, (3) Identify novel neural targets and validate pharmacological compounds that may be used to treat problems associated with alcohol and drug abuse. The lab culture is collaborative and dynamic, innovative, and team-based. We are looking for colleagues who share an interest in understanding how alcohol hijacks reward pathways to produce addiction.

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

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

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

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

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

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.

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.

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

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

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.

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.

Life is animate and three-dimensional.  Our lab develops tools to better understand living specimens at single molecule, cellular, and tissue level length scales.  Our current efforts comprise three synergistic research areas: 1) development and application of novel fluorescent imaging modalities including: super resolution, light sheet, and adaptive optical microscopy 2) investigation of how mechanical forces and cytoskeletal dynamics drive cancer cell migration through complex three-dimensional environments, and 3) generation of microfabricated platforms to precisely control the cellular microenvironment for tissue engineering and drug screening.

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.

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

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

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

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.

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.

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.  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.

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.

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.

Dr. McCullough’s lab takes a translational research approach that incorporates primary cell and organotypic in vitromodels with clinical research (controlled human exposures) to study the role of cellular and molecular mechanisms in mediating the local and systemic effects of exposure to inhaled chemicals.  His laboratory utilizes primary cell/organotypic in vitro models, live cell imaging of fluorescent biosensors, and both traditional and advanced molecular biology/biochemistry methods to characterize the relationship between redox dysfunction/oxidative stress, inflammation, cell signaling pathway activation, epigenetic changes, gene expression, and cell-specific functional outcomes.  In addition to identifying the mechanisms involved in the effects of toxic exposures, Dr. McCullough’s research also aims to identify biomarkers of toxic exposure effects, predicting susceptible populations, and identifying factors that can be used to mitigate adverse exposure outcomes.

We focus on the translational potential and clinical impact of biomedical research. Our general research interest is to reveal the mechanisms of eye diseases using animal and other research models. One current project is to investigate the markers of limbal stem cells using transgenic mice. The lack of limbal stem cell marker has been a long-term bottleneck in the diagnosis and treatment of limbal stem cell deficiency, which leads to a loss of corneal epithelial integrity and damaged limbal barrier functions with the symptoms of persistent corneal epithelial defects, pain, and blurred vision. The research results will directly impact on the early-stage diagnosis of the disease and the quality control of ex vivo expanded limbal stem cells for transplantation.

Our lab focuses on the life cycle of cancer-associated human papillomaviruses (HPV); small DNA viruses that exhibit a strict tropism for the epithelium. Several studies in our lab focus on the interface of HPV with cellular DNA damage response (DDR) pathways and how HPV manipulates DNA repair pathways to facilitate viral replication. We are also interested in understanding how the viral life cycle is epigenetically regulated by the DDR as well as by other chromatin modifiers. Additionally, we are investigating how HPV regulates the innate immune response throughout the viral life cycle.

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.

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.

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

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.

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.

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.

Dr. Rizvi’s expertise is in imaging and therapeutic applications of light, bioengineered 3D models and animal models for cancer, and targeted drug delivery for inhibition of molecular survival pathways in tumors. His K99/R00 (NCI) develops photodynamic therapy (PDT)-based combinations against molecular pathways that are altered by fluid stress in ovarian cancer. He has co-authored 46 peer-reviewed publications and 5 book chapters with a focus on PDT, biomedical optics, and molecular targeting in cancer.

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.

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

Our 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.

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.

By 2035, more than 500 million people worldwide will be diagnosed with diabetes. Individuals with diabetes are prone to frequent and invasive infections that commonly manifest as skin and soft tissue infections (SSTIs). Staphylococcus aureus is the most commonly isolated pathogen from diabetic SSTI. S. aureus is a problematic pathogen that is responsible for tens of thousands of invasive infections and deaths annually in the US. Most S. aureus infections manifest as skin and soft tissue infections (SSTIs) that are usually self-resolving. However, in patients with comorbidities, particularly diabetes, S. aureus SSTIs can disseminate resulting in systemic disease including osteomyelitis, endocarditis and sepsis. The goal of my research is to understand the complex interactions between bacterial pathogens and the host innate immune response with focus on S. aureus and invasive infections associated with diabetes. My research is roughly divided into two project areas in order to understand the contributions of the pathogen and the host response to invasive infections associated with diabetes. Project 1: Defining mechanisms of immune suppression in diabetic infections. Project 2: Determine the role of bacterial metabolism in virulence potential and pathogenesis.

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.

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.

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.

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).

My research interests are focused on mechanisms associated with altered innate immune functions, which lead to dysregulated adaptive immunity. Currently my research program has three major arms integrated through with a central philosophy. Specifically, our laboratory focuses on the contribution of epithelial cell biology and signaling to innate and adaptive immune homeostasis and dysfunction. We study the contribution of what I term ‘epithelial cell innate immune (dys)function’ to three major disease conditions: pancreatic cancer, type 1 diabetes (autoimmunity), and periodontal disease (autoinflammation). While appearing to be a diverse research program, we have found that many of the mechanisms and systems in play are surprisingly (or maybe not so surprisingly) similar allowing for rapid translation of our findings. Importantly, previous investigations into the role of epithelial cells in immunobiology have been hindered by a lack of robust primary cell culture techniques, which our laboratory has been able to overcome using both animal and human tissues. Thus, using our novel and unique tools we are able to evaluate our findings in the human conditions, again making translation of our findings that much more feasible. In addition to my primary research objectives, my collaborative research programs, have allowed me to be involved, at some level, in investigating the basic biology of health, multiple autoimmune conditions, autoinflammation, sepsis, and exercise induced inflammation I have been blessed with the opportunities to couple my passions and expertise with that of others to bring together multiple research communities with the goal of advancing human health and hope to be able to continue to do so for years to come.

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).

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.

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.

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.

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.