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[ Phd Program: Pharmacology ]

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NameEmailPhd ProgramResearch InterestsPublications
Allbritton, Nancy email , , , , publications

The overall focus of the laboratory is to quantitatively measure the activity of proteins in cellular signaling networks to understand the relationships of these intracellular pathways in regulating cell health and disease. These networks are composed of interacting proteins and small molecules that work together in a concerted manner to regulate the cell in response to its environment. Despite the importance of these key signaling molecules in controlling the behavior of cells, most of these proteins and metabolites can not be quantified in single cells. There is a need throughout biology for new technologies to identify and understand the molecular circuits within single cells. A research goal is to develop new methods that will broaden the range of measurements possible at the single-cell level and then to utilize these methods to address fundamental biologic questions. We are pursuing this task by bringing to bear diverse techniques from chemistry, physics, biology and engineering to develop new analytical tools to track signal transduction within individual cells. Our research is a multidisciplinary program for the development and application of new analytical methods with two main focus areas: 1) techniques to monitor cellular signaling, and 2) microfabricated cellular analysis systems.

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

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

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

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.

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

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

Church, Frank C. email , , , , , , publications

Our research is concerned with proteases and their inhibitors in various disease processes (thrombosis and cancer); our science tools are structure-activity, cell biology and signaling, pathobiology, immunohistochemistry, and in vivo models.

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.

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.

DeSimone, Joseph M. email , , , , publications

The direct fabrication and harvesting of monodisperse, shape-specific nano-biomaterials are presently being designed to reach new understandings and therapies in cancer prevention, diagnosis and treatment.  Students interested in a rotation in the DeSimone group should not contact Dr. DeSimone directly.  Instead please contact Chris Luft at jluft@email.unc.edu.

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.

Earp, H. Shelton email , , , publications

Our lab is interested in how signals from membrane receptors are transduced to the nucleus altering gene expression, cell shape, proliferation and differentiation. We are particularly interested in tyrosine-specific protein kinases in breast and prostate cancer, as well as lymphoma/leukemia. Particular focus of the lab include the roles of :1) the EGF receptor family and related molecules e.g. HER4/ErbB4 in growth inhibition and differentiation, 2) the intracellular tyrosine kinase Ack which tyrosine phosphorylates the androgen receptor in androgen-independent prostate cancer and 3) a receptor tyrosine kinase that we cloned, Mer, that is expressed ectopically in childhood leukemias conferring a chemoresistant signal.  Mer also function in tumor-associated macrophages in a manner that appears to enhance tumor growth and immune system evasion.

Elston, Timothy email , , , , publications

The Elston lab is interested in understanding the dynamics of complex biological systems, and developing reliable mathematical models that capture the essential components of these systems. The projects in the lab encompass a wide variety of biological phenomena including signaling through MAPK pathways, noise in gene regulatory networks, airway surface volume regulation, and understanding energy transduction in motor proteins. A major focus of our research is understanding the role of molecular level noise in cellular and molecular processes. We have developed the software tool BioNetS to accurately and efficiently simulate stochastic models of biochemical networks

Emanuele, Michael email , , , , , publications

Our lab applies cutting edge genetic and proteomic technologies to unravel dynamic signaling networks involved in cell proliferation, genome stability and cancer. These powerful technologies are used to systematically interrogate the ubiquitin proteasome system (UPS), and allow us to gain a systems level understanding of the cell at unparalleled depth. We are focused on UPS signaling in cell cycle progression and genome stability, since these pathways are universally perturbed in cancer.

Graves, Lee M. email , , , , publications

Our lab is studying the role of mitogen and stress-activated protein kinases to regulate key aspects of cell metabolism. We are also studying signalling by tyrosine kinases in response to toxicological agents or cell stress.

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.

Herman, Melissa email , , , , publications

My research interests involve the structure of inhibitory neuronal networks and how these networks change to produce adverse behavioral outcomes. My main interest is how the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) regulates neuronal networks via both synaptic and extrasynaptic forms of inhibition and how alterations in inhibitory networks contribute to clinical conditions such as alcohol use disorder, nicotine, addiction, or stress. My work has focused primarily on three brain regions: the nucleus tractus solitaries (NTS), central and basolateral amygdala, and ventral tegmental area. In each of these areas I have identified local inhibitory networks that control overall excitability and that are dysregulated by exposure to acute and or chronic exposure to alcohol or nicotine.

Hodge, Clyde email , , , , , publications

The primary goal of our research is to elucidate the neurobiological systems that mediate the behavioral effects of alcohol and drugs of abuse.

Johnson, Gary L. email , , , , publications

Spatio-temporal regulation of signal relay systems in cells using live cell fluorescence imaging and targeted gene disruption of signaling proteins to define their role in development, physiology and pathophysiology.

Jones, Alan email , , , , , , , publications

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

Kash, Thomas email , , , , , , publications

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

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.

Maixner, William email , , , publications

Dr. Maixner’s research program focuses on identifying the pathophysiological processes that underlie pain perception, persistent pain conditions, and related disorders. His current research focuses on genetic, environmental, biological, and psychological risk factors that contribute to the onset and maintenance of chronic pain conditions. A long term goal of his program is to translate new discoveries into clinical practices that improve the ability to diagnose and treat patients experiencing chronic pain.

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.

McCarthy, Ken email , , , , , publications

Investigating the role of astrocyte signaling in brain function.

Morrow, Leslie email , , , , , , publications

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

Nicholas, Robert A. email , , , , , , publications

My laboratory has two main interests: 1) Regulation of P2Y receptor signaling and trafficking in epithelial cells and platelets. Our laboratory investigates the cellular and molecular mechanisms by which P2Y receptors are differentially targeted to distinct membrane surfaces of polarized epithelial cells and the regulation of P2Y receptor signaling during ADP-promoted platelet aggregation. 2) Antibiotic resistance mechanisms. We investigate the mechanisms of antibiotic resistance in the pathogenic bacterium, Neisseria gonorrhoeae. Our laboratory investigates how acquisition of mutant alleles of existing genes confers resistance to penicillin and cephalosporins. We also study the biosynthesis of the gonococcal Type IV pilus and its contribution to antibiotic resistance.

Parise, Leslie email , , , , , , , , publications

The overall goal of our laboratory is to understand the molecular interface between cell signaling and adhesion receptors in blood diseases and cancer in order to develop novel therapeutic targets and approaches. One area of study is platelets because they become activated by cellular signals and adhere to each other and the blood vessel wall via specific adhesion receptors. These events can block blood flow, causing heart attacks and stroke, the leading causes of death in the US. Another area of research is sickle cell disease, since red blood cells in these patients are abnormally adhesive and also cause blood vessel blockages. A third area is cancer since cancer cells use similar cellular signals and adhesion receptors in tumorigenesis and metastasis. Our work involves a wide array  of technologies that include molecular, structural and cellular approaches as well as clinical/translational studies with human patients.

Roth, Bryan email , , , publications

The ultimate goal of our studies is to discover novel ways to treat human disease using G-protein coupled receptors.

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.

Samulski, Jude email , , , , , publications

We are engaged in studying the molecular biology of the human parvovirus adeno-associated virus (AAV) with the intent to using this virus for developing a novel, safe, and efficient delivery system for human gene therapy.

Schisler, Jonathan C. email , , , , publications

The Schisler Lab is geared towards understanding and designing therapies for diseases involving proteinopathies- pathologies stemming from protein misfolding, aggregation, and disruption of protein quality control pathways. We focus on cardiovascular diseases including the now more appreciated overlap with neurological diseases such as CHIPopathy (or SCAR16, discovered here in our lab) and polyQ diseases. We use molecular, cellular, and animal-based models often in combination with clinical datasets to help drive our understanding of disease in translation to new therapies.

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.

Song, Juan email , , , , publications

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

Wang, Andrew Z. email , , , , publications

My laboratory has two research directions. One is to utilize nanotechnology to develop novel diagnostics and therapeutics to improve cancer treatment. The other is to use techniques developed in tissue engineering to develop in vitro 3D models of cancer metastasis.

Yeh, Jen Jen email , , , , publications

We are a translational research lab. The overall goal of our research is to find therapeutic targets and biomarkers for patients with pancreatic and colorectal cancer and to translate this to the clinic. In order to accomplish this, we analyze patient tumors using microarray analysis, identify and validate targets using forward and reverse genetic approaches in both cell lines and mouse models. At the same time, we evaluate novel therapeutics for promising targets in mouse models in order to better predict clinical response in humans. We also collaborate with the DeSimone and Huang labs to apply nanotechnology to drug delivery and therapeutics. Keywords: genomics, biomarkers, translational research, microarray, signaling, pancreatic cancer, colon cancer, mouse models, GEMM, drug discovery, nanoparticles.

Zhang, Yanping email , , , , , publications

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