BBSP Faculty

Our research group utilizes the nematode C. elegans to investigate germ cell immortality: mechanisms that allow germ cells remain eternally youthful as they are transmitted from one generation to the next. We also study how telomerase functions at chromosome termini, as well as the consequences of telomere dysfunction.

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

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

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

My research group is broadly interested in the application of sequencing technologies in medical genetics and genomics, using a combination of wet lab and computational approaches.  As a clinician, I am actively involved in the care of patients with hereditary disorders, and the research questions that my group investigates have direct relevance to patient care.  One project uses genome sequencing in families with likely hereditary cancer susceptibility in order to identify novel genes that may be involved in monogenic forms of cancer predisposition.  Another major avenue of investigation examines the use of genome-scale sequencing in clinical medicine, ranging from diagnostic testing to newborn screening, to screening in healthy adults.

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

Our long-term goal is to define the molecular mechanisms of two-component regulatory systems, which are utilized for signal transduction by bacteria, archaea, eukaryotic microorganisms, and plants. Our current focus is to identify and understand the features that control the rates of several different types of protein phosphorylation and dephosphorylation reactions. The kinetics of phosphotransfer reactions can vary dramatically between different pathways and reflect the need to synchronize biological responses (e.g. behavior, development, physiology, virulence) to environmental stimuli. Member of the Molecular & Cellular Biophysics Training Program.

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

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

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.

Experimental Evolution of Viruses. We use both computational and experimental approaches to understand how viruses adapt to their host environment. Our research attempts to determine how genome complexity constrains adaptation, and how virus ecology and genetics interact to determine whether a virus will shift to utilizing new host. In addition, we are trying to develop a framework for predicting which virus genes will contribute to adaptation in particular ecological scenarios such as frequent co-infection of hosts by multiple virus strains. For more information, and for advice on applying to graduate school at UNC, check out my lab website www.unc.edu/~cburch/lab.

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.

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 goal of our research is to understand how astrocytes develop and how they interact with neural elements during nervous system formation, function, and maintenance. Our lab uses fruit fly Drosophila and zebrafish Danio rerio to explore fundamental aspects of astrocyte biology. We leverage the powerful genetics and unparalleled molecular toolsets in flies to uncover gene function, and we exploit the advanced live-imaging techniques in zebrafish to study astrocyte-neuron interactions in vivo.

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

My lab is focused on the improvement of treatment of chronic bacterial infections. We aim to determine the mechanisms of antibiotic tolerance. Our aim is to understand the physiology of the bacterial cell, primarily Staphylococcus aureus, during infection and how this physiology allows the cell to survive lethal doses of antibiotic. We will use advanced methods such as single cell analysis and Tn-seq to determine the factors that facilitate survival in the antibiotic’s presence. Once we understand this tolerance, we will develop advanced screens to identify novel compounds that can be developed into therapeutics that can kill these drug tolerant “persister” cells and eradicate deep-seated infections.

Males and females differ in their prelevance, treatment, and survival to a diverse set of human disease states. This is exemplified cardiovascular disease, a disease that takes more lives than all forms of cancer combined. In cardiac disease, women almost uniformly fare far worse than men: as of 2007 one woman dying for cardiovascular disease in the US every minute. Our lab focuses on sex disparities in development and disease. For these studies, we use a highly integrated approach that incorporates developmental, genetic, proteomic, biochemical and molecular-based studies in mouse and stem cells. Recent advances by our past students (presently at Harvard, John Hopkins and NIH) include studies that define the cellular and molecular events that lead to cardiac septation, those that explore cardiac interaction networks as determinants of transcriptional specificity, the mechanism and function of cardiac transcriptional repression networks, and the regulatory networks of cardiac sexual dimorphism. Our lab has opening for rotation and PhDs to study these rapidly emerging topics.

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.

The primary research area my lab is the regulation of meiotic recombination at the genomic level in higher eukaryotes. Genomic instability and disease states, including cancer, can occur if the cell fails to properly regulate recombination. We have created novel tools that give our lab an unparalleled ability to find mutants in genes that control recombination. We use a combination of genetics, bioinformatics, computational biology, cell biology and genomics in our investigations. A second research area in the lab is the role of centromere DNA in chromosome biology. We welcome undergraduates, graduate students, postdoctoral fellows and visiting scientists to join our team.

Dr. Cotter’s research is aimed at understanding molecular mechanisms of bacterial pathogenesis. Using Bordetella species as models, her group is studying the role of virulence gene regulation in respiratory pathogenesis, how virulence factors activate and suppress inflammation in the respiratory tract, and how proteins of the Two Partner Secretion pathway family are secreted to the bacterial surface and into the extracellular environment. A second major project is focused on Burkholderia pseudomallei, an emerging infectious disease and potential biothreat agent. This research is aimed at understanding the role of autotransporter proteins in the ability of this organism to cause disease via the respiratory route.

We use the premier model plant species, Arabidopsis thaliana, and real world plant pathogens like the bacteria Pseudomonas syringae and the oomycete Hyaloperonospora parasitica to understand the molecular nature of the plant immune system, the diversity of pathogen virulence systems, and the evolutionary mechanisms that influence plant-pathogen interactions. All of our study organisms are sequenced, making the tools of genomics accessible.

With a particular interest in pediatric solid tumors, our lab aims to develop a mechanistic understanding of the role of aberrant or dysregulated transcription factors in oncogenesis.

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.

The work focuses on how air pollutants affect human health, the role of genetics and epigenetic factors in determining susceptibility and clinical/dietary strategies to mitigate these effects. There is a strong emphasis on translational research projects using a multi-disciplinary approach. Thus, by using human in vivo models (such as clinical studies) we validate in vitro, epidemiology, and animal findings.

Sleep is an essential and evolutionarily conserved process that modifies synapses in the brain to support cognitive functions such as learning and memory. We are interested in understanding the molecular mechanisms of synaptic plasticity with a particular interest in sleep. Using mouse models of human disease as well as primary cultured neurons, we are applying this work to understanding and treating neurodevelopmental disorders including autism and intellectual disability. The lab focuses on biochemistry, pharmacology, animal behavior and genetics.

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

The research in my lab is divided into two main areas – 1) Atomic force microscopy and fluorescence studies of protein-protein and protein-nucleic acid interactions, and 2) Mechanistic studies of transcription elongation. My research spans the biochemical, biophysical, and analytical regimes.

Yeast molecular genetics; MAP-Kinease activation pathways; regulation of cell differentiation.

In the Ferris lab, we use genetically diverse mouse strains to better understand the role of genetic variation in immune responses to a variety of insults. We then study these variants mechanistically. We also develop genetic and genomic datasets and resources to better identify genetic features associated with these immunological differences.

Our laboratory studies the role of the blood coagulation system in inflammatory, infectious, and malignant disease. Specifically, we are interested in better defining the roles of factors such as prothrombin, fibrinogen and plasminogen in driving disease processes in the contexts of pancreatic ductal adenocarcinoma (PDAC), Staphylococcus aureus infection, and obesity/metabolic syndrome. Current studies suggest that coagulation factors drive mechanisms of disease both dependent and independent of their traditional roles in hemostasis and thrombosis. Our overall goal is to translate this knowledge into novel approaches for treating these common yet deadly diseases.

The lab focuses on understanding how environmental exposures are associated with human disease with a particular focus on genomic and epigenomic perturbations. Using environmental toxicogenomics and systems biology approaches, we aim to identify key molecular pathways that associate environmental exposure with diseases. A current focus in the lab is to study prenatal exposure to various types of metals including arsenic, cadmium, and lead. We aim to understand molecular mechanisms by which such early exposures are associated with long-term health effects in humans. For example, we are examining DNA methylation (epigenetic) profiles in humans exposed to metals during the prenatal period. This research will enable the identification of gene and epigenetic biomarkers of metal exposure. The identified genes can serve as targets for study to unravel potential molecular bases for metal-induced disease. Ultimately, we aim to identify mechanisms of metal -induced disease and the basis for inter-individual disease susceptibility.

Dr. Gilmore’s research group is applying state-of–the-art magnetic resonance imaging and image analysis techniques to study human brain development in 0-6 year olds.  Approaches include structural, diffusion tensor, and resting state functional imaging, with a focus on cortical gray and white matter development and its relationship to cognitive development.  Studies include normally developing children, twins, and children at high risk for schizophrenia and bipolar illness.  We also study the contributions of genetic and environmental risk factors to early brain development in humans.  A developing collaborative project with Flavio Frohlich, PhD will use imaging to study white and gray matter development in ferrets and its relationship with cortical oscillatory network 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.

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

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

The Gordon lab is brand new to UNC, and studies stem cell and stem cell niche biology in the model organism C. elegans. The germ line stem cells make the gametes, which make the next generation of worms. These cells are therefore at the nexus of development, genetics, and evolution. We will be getting started with projects pertaining to evolutionary comparative gene expression in the stem cells and stem cell niche and niche development. The techniques we use include molecular biology, CRISPR/Cas9-mediated genome editing, worm genetics, and microscopy.

Gordon-Larsen’s work integrates biology, behavior, and environment to understand, prevent and treat obesity, cardiovascular and cardiometabolic diseases. She works with biomarker, microbiome, metabolome, genetic, weight, diet, and environment data using multilevel modeling and pathway-based analyses. She works with several longitudinal cohorts that span more than 30 years. Most of her work uses data from the US and China. Her research teams include a wide variety of scientists working in areas such as genetics, medicine, bioinformatics, biostatistics, microbiology, nutrition, and epidemiology.

Our lab studies pathways that regulate genome instability in cancer, which is a cancer hallmark associated with clinically aggressive disease. We utilize CRISPR-enhanced murine models of breast cancer to interrogate the impact of DNA damage response gene mutations on cancer pathogenesis and therapeutic susceptibility. We have identified an alternative DNA double strand break repair pathway as a driver of genome instability in a subset of breast cancers, and are investigating its potential as a therapeutic target.  We also study how deficiencies in DNA repair can impact responsiveness to immunotherapy. Finally, we have developed sensitive assays for detecting circulating tumor DNA (i.e., “liquid biopsy”) in cancer patients, with an interest in validating predictive biomarkers for personalized cancer therapy.  These translational studies are currently being performed in patients with breast cancer and cancers that arise in the head/neck.

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.

We study alphavirus infection to model virus-induced disease.  Projects include 1) mapping viral determinants involved in encephalitis, and 2) using a mouse model of virus-induced arthritis to identify viral and host factors associated with disease.

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

Our lab works with adeno-associated viral vectors for both the characterization of vector and host responses upon transduction and as therapeutic agents for the treatment of genetic diseases.  In particular, we tend to focus on the 145 nucleotide viral inverted terminal repeats of the transgenic genome and their multiple functions including the replication initiation, inherent promoter activity, and stimulation of intra/inter molecular DNA repair pathways.  The modification of the AAV ITRs by synthetic sequences imparts unique functions/activities rendering these synthetic vectors perhaps better suited for therapeutic applications.

My research interest is in genomic characterization and integrative genomic approaches to better understand cancer. My group is part of the NCI Genome Data Analysis Center focused on RNA expression analysis. We have a number of ongoing projects including developing molecular classifications for potential clinical utility, developing methods for deconvolution to understand bulk tissue heterogeneity, analysis of driver negative cancers, and analysis of ancestry markers with cancer features.

The lab focus is to understand the mechanism of gene-environment interactions by examining the genetic basis of epigenetic response to nutrition and environmental toxicants. The long-term goal is to identify and characterize genetic (naturally occurring and induced) and environmental (toxicant and nutritional) causes of disruption of DNA methylation patterns during development and to determine their role in disease. The primary focus is on DNA methylation patterns during germ cell and early embryonic development during critical windows of epigenetic reprogramming.

The goal of my research is to identify, clone, and characterize the evolution of genes underlying natural adaptations in order to determine the types of genes involved, how many and what types of genetic changes occurred, and the evolutionary history of these changes. Specific areas of research include: 1) Genetic analyses of adaptations and interspecific differences in Drosophila, 2) Molecular evolution and population genetics of new genes and 3) Evolutionary analysis of QTL and genomic data.

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.

We use studies of HIV/SIV evolution to reveal information about viral dynamics in vivo. This typically involves genetic and/or phenotypic analyses of viral populations in samples from HIV-infected humans or SIV-infected nonhuman primates (NHPs). We are currently exploring the mechanisms that contribute to neurocognitive impairment in HIV-infected people by sequencing viral populations in the CNS of humans and NHPs not on antiretroviral therapy. We are also using these approaches to examine viral populations that persist during long-term antiretroviral therapy in an effort to better understand the viral reservoirs that must be targeted in order to cure HIV-infected people.

Despite recent success in reducing malaria transmission, the estimated annual numbers of malaria infections (~225 million) and deaths (~781,000) remain high. Despite this immense burden, our understanding of the genetic diversity of malaria and the factors that promote this diversity is limited.  This diversity among plasmodial parasites has a critical impact on many factors involved in the control of infections, including: 1) development of drug resistance, 2) development of naturally acquired immunity, and 3) vaccine design.  My laboratory’s primary interests are: 1) describing the genetic diversity of P. falciparum using molecular biological and next generation sequencing tools, and 2) using these data to understand the evolutionary and ecological factors that drive this diversity, promote the emergence of drug resistance and affect our ability to effectively develop immunity.

Our lab is focused on the development of HIV-1 vectors for gene therapy of genetic disease.  In addition, we are using the vector system to study HIV-1 biology.  We are also interested in utilizing the HIV-1 vector system for functional genomics.

My research aims at prevention and treatment of cardiovascular diseases and focuses on the identification of genes that confer susceptibility or resistance to the diseases with the use of genetically engineered mice. In collaboration with Dr.Oliver Smithies, I very recently developed a new method for altering gene expression by modifying 3’ untranslated regions in mice which enables fine-tuned modification of gene expression. I am now analyzing the phenotypes of several mouse models generated with this method.

While both genes and environment are thought to influence human health, most investigations of complex disease only examine one of these risk factors in isolation.  Accounting for both types of risk factors and their complex interactions allows for a more holistic view of complex disease causation.  The Kelada lab is focused on the identification and characterization of these gene-environment interactions in airway diseases, particularly asthma, a disorder of major public health importance.   /  / Additionally, to gain insight into how the airway responds to relevant exposures (e.g., allergens or pathogens), we study gene expression in the lung (particularly airway epithelia). Our goal is identify the genetic determinants of gene expression by measuring gene expression across many individuals (genotypes). / This “systems genetics” approach allows us to identify master regulators of gene expression that may underlie disease susceptibility or represent novel therapeutic targets. /

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

Craig Lee, Pharm.D, Ph.D. is a professor in the UNC Eshelman School of Pharmacy’s Division of Pharmacotherapy and Experimental Therapeutics (DPET). A key aspect of DPET’s mission is to optimize drug therapy through translating experimental and clinical pharmacology discoveries into precision medicine and accelerating application of these discoveries to improve patient care.

Dr. Lee is trained as a clinical/translational pharmaceutical scientist with expertise in cytochrome P450 metabolism, cardiovascular experimental therapeutics, and precision medicine/pharmacogenomics. He is an active member of the UNC McAllister Heart Institute and UNC Program for Precision Medicine in Healthcare, and has an adjunct faculty appointment in the UNC School of Medicine’s Division of Cardiology.

The overall objective of Dr. Lee’s research program is to improve the understanding of the central mechanisms underlying inter-individual variability in drug response as a means to develop novel therapeutic strategies that will improve public health. A major scientific focus of the Lee laboratory is the metabolism of drugs and eicosanoids by the cytochromes P450 enzyme system. The major therapeutic area of application of their research is cardiovascular and metabolic disease.

The Lee laboratory seeks to identify and elucidate the key factors that exacerbate inter-individual variability in the metabolism of and response to drugs currently on the market, and determine whether implementation of genomic and biomarker-guided drug selection and dosing strategies can reduce this variability in metabolism and response and improve patient outcomes. The Lee laboratory also seeks to develop a thorough understanding of how cytochrome P450-derived eicosanoids (bioactive lipid mediators of arachidonic acid) regulate hepatic and extra-hepatic inflammatory responses, and determine whether modulation of this pathway will serve as an effective anti-inflammatory and end-organ protective therapeutic strategy for cardiovascular and metabolic disease. Using genomics and biomarkers, the lab seeks to translate their preclinical discoveries into humans and determine which subsets of the population may be most likely to respond to the therapeutic strategies under evaluation in the laboratory.

The Lee laboratory is a highly collaborative and translational research program that integrates mechanistically-driven rodent and cell-based preclinical models with observational and interventional clinical studies. They have received funding from the National Institutes of Health and American Heart Association, authored over 100 manuscripts and over 100 abstracts in the areas of cytochromes P450, eicosanoid and drug metabolism, pharmacogenomics, and experimental therapeutics. Dr. Lee has served as the major research advisor for over 40 graduate students, post-doctoral fellows, and professional students.

The Yun Li group develops statistical methods and computational tools for modern genetic, genomic, and epigenomic data. We do both method development and real data applications. The actual projects in the lab vary from year to year because I am motivated by real data problems, and genomics is arguably (few people argue with me though) THE most fascinating field with new types and huge amount of data generated at a pace more than what we can currently deal with. For current projects, please see: https://yunliweb.its.unc.edu/JobPostings.html

Dr. Lin is an infectious disease physician-scientist whose research lies at the interface of clinical and molecular studies on malaria. My current projects focus on 1) determinants of malaria transmission from human hosts to mosquitos and 2) the epidemiology and relapse patterns of Plasmodium ovale in East Africa. Work in my lab involves applying molecular tools (real-time PCR, amplicon deep sequencing, whole genome sequencing, and to a lesser extent antigen and antibody assays) to samples collected in clinical field studies to learn about malaria epidemiology, transmission, and pathogenesis.

Trauma and stress are common in life. While most individuals recover following trauma/stress exposure, a substantial subset will go on to develop adverse neuropsychiatric outcomes such as chronic pain, posttraumatic stress disorder (PTSD), depression, and postconcussive symptoms. Our research is focused on understanding individual vulnerability to such outcomes and to identify novel biomarkers and targets for therapeutic intervention. We use translational research approaches, including bioinformatics analysis of large prospective human cohort data, animal model research, and systems and molecular biology to better understand pathogenic mechanisms. We are particularly interested in the genetic and psychiatric/social factors influencing adverse outcome development, as well as biological sex differences that contribute to higher rates of these outcomes in women vs men.

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.

Traditionally, basic science has sought to enter the translational pipeline through what can be referred to as “Bottom-Up” science, that is, studies that start with a hypothesis in the lab and aim to develop clinical relevance of the findings. In some cases, notably in conventional antibiotic development, this has worked well – but it assumes one-size fits all solutions that are only as good as our assumptions about the biology of many infectious diseases such as tuberculosis. By contrast, my research focuses on a “Top-Down” approach, leveraging the power of bacterial population genomics to identify bacterial processes important for Mtb success in people and to then employ cutting-edge experimental techniques to mechanistically dissect these processes with the goal of leveraging them using new translational tools.

In my work to date, I have applied this “Top-Down” strategy to define bacterial determinants of treatment outcomes and transmission success, as evident in first-author/corresponding author publications in prestigious journals such as Science, Nature Ecology Evolution, Cell Host Microbe, Science Advances, Genome Biology, PNAS, etc. My work combines expertise in evolutionary biology and bacterial genomics, cutting-edge bacterial genetics and high-throughput experimental phenotyping.

In my own lab, I will use these tools to (1) define the biological mechanisms that enable Mtb to survive antibiotic treatment; (2) identify bacterial determinants of TB transmission success; and (3) elucidate the evolutionary mechanisms underlying the emergence of new bacterial pathogens.

The Love Lab uses statistical models to infer biologically meaningful patterns in high-dimensional datasets, and develops open-source statistical software for the Bioconductor Project. At UNC-Chapel Hill, we often collaborate with groups in the Genetics Department and the Lineberger Comprehensive Cancer Center, studying how genetic variants relevant to diseases are associated with changes in molecular and cellular phenotypes.

Overall goal of our research is to gain better knowledge of gene-gene and gene-environment interactions in common cardiovascular conditions in humans. We have been modifying mouse genome in such a way that resulting mice can model quantitative variations of a specific gene product that occur in human population. With these mice, we explore causes, mechanisms, and nutritional treatments of cardiovascular complications resulted from common conditions such as diabetes, lung infections, and pregnancy-associated hypertension. Current focus is on the oxidative stress and effects of vitamin B12 as antioxidant and beyond.

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

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

We are interested in the mechanisms by which histone protein synthesis is coupled to DNA replication, both in mammalian cell cycle and during early embryogenesis in Drosophila, Xenopus and sea urchins.

The research in our laboratory focuses on epigenetics and RNA processing. In particular, we are interested in the roles of small ribonucleoproteins (RNPs) and histone post-translational modifications in the regulation of eukaryotic gene expression.  There are two main projects in the lab. (1) We have created a comprehensive genetic platform for histone gene replacement that — for the first time in any multicellular eukaryote — allows us to directly determine the extent to which histone post-translational modifications contribute to cell growth and development. (2) We study an RNP assembly factor (called Survival Motor Neuron, SMN) and its role in neuromuscular development and a genetic disease called Spinal Muscular Atrophy (SMA). Current work is aimed at a molecular understanding of SMN’s function in spliceosomal snRNP assembly and its dysfunction in SMA pathophysiology.

My research program studies how species form. We use a combination of approaches that range from field biology, behavior, and computational biology.

Research in the lab focuses on how a single genome gives rise to a variety of cell types and body parts during development. We use Drosophila as an experimental system to investigate (1) how transcription factors access DNA to regulate complex patterns of gene expression, and (2) how post-translational modification of histones contributes to maintenance of gene expression programs over time. We combine genomic approaches (e.g. CUT&RUN/ChIP, FAIRE/ATAC followed by high-throughput sequencing) with Drosophila genetics and transgenesis to address both of these questions.

Molecular genetic analysis of virulence of Yersinia and Klebsiella: My laboratory uses Yersinia enterocolitica, Y. pestis, and Klebsiella as model systems to study bacterial pathogenesis. The long-term goals of our work are to understand the bacteria-host interaction at the molecular level to learn how this interaction affects the pathogenesis of infections and to understand how these pathogens co-ordinate the expression of virulence determinants during an infection. To do this we use genetic, molecular and immunological approaches in conjunction with the mouse model of infection.

The Miller lab is working to improve the efficacy of immunotherapy to treat cancer. We aim to develop personalized immunotherapy approaches based on a patient’s unique cancer mutations. We have a particular interest in myeloid cells, a poorly understood group of innate immune cells that regulate nearly all aspects of the immune response. Using patient samples, mouse models, single-cell profiling, and functional genomics approaches, we are working to identify novel myeloid-directed therapies that allow us to overcome resistance and successfully treat more patients.

We identify genetic variants that influence common human traits with complex inheritance patterns, and we examine the molecular and biological mechanisms of the identified variants and the genes they affect. Currently we are investigating susceptibility to type 2 diabetes and obesity, and variation in cholesterol levels, body size, body shape, and metabolic traits. We detect allelic differences in chromatin structure and gene expression and examine gene function in human cell lines and tissues. In addition to examining the primary effects of genes, the lab is exploring the interaction of genes with environmental risk factors in disease pathogenesis. Approaches include genome-wide association studies, molecular biology, cell biology, genetic epidemiology, sequencing, and bioinformatic analysis of genome-wide data sets.

The Morris lab leverages flexible mouse models of hard to treat cancers of the pancreas and liver to identify how cancer drivers perturb evolutionarily selected developmental programs and how such programs may be re-normalized. We focus on (1) the relationship between tumor suppressor pathways and the epigenetic determinants of cell plasticity, (2) evolutionary routes unleashed by specific tumor suppressor loss, and (3) how diversification at both the epigenetic and genomic level contribute to cancer development and therapeutic response.

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.

My research focuses on understanding the relationship between dermal and inhalation exposure and the effect of individual genetic differences on the function of enzymes that detoxify hazardous agents and that affect the development of disease. My research group has pioneered approaches to quantitatively measure skin and inhalation exposures to toxicants; additionally, my group has developed sophisticated exposure modeling tools using mathematical and statistical principles in an effort to standardize and improve exposure and risk assessment.

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

Non-Mendelian genetics including, meiotic drive, parent-of-orifin effects and allelic exclusion.

Our research focuses on the genetic and cellular mechanisms that underlie how prenatal exposure to alcohol and other drugs, such as cannabinoids, disrupt normal brain development. We use a wide variety of molecular and cell biology tools including RNA-seq (whole transcriptomic profiling), mouse transgenics, and confocal imaging to understand how drugs alter cell signaling pathways and transcriptional regulation in development. Our work also studies key regulatory pathways, such as Sonic hedgehog (Shh) and other primary cilia-mediated signals, during normal and aberrant embryonic development.

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: https://proxy.qualtrics.com/proxy/?url=http%3A%2F%2Fpeiferlab.web.unc.edu%2F&token=1rPNJvHEEfhAAiwkSviuOG0Fg8%2ByN3Q3GMob1A2GJwM%3D

The focus of my lab is to characterize the biological diversity of human tumors using genomics, genetics, and cell biology, and then to use this information to develop improved treatments that are specific for each tumor subtype and for each patient. A significant contribution of ours towards the goal of personalized medicine has been in the genomic characterization of human breast tumors, which identified the Intrinsic Subtypes of Breast Cancer. We study many human solid tumor disease types using multiple experimental approaches including RNA-sequencing (RNA-seq), DNA exome sequencing, Whole Genome Sequencing, cell/tissue culturing, and Proteomics, with a particular focus on the Basal-like/Triple Negative Breast Cancer subtype. In addition, we are mimicking these human tumor alterations in Genetically Engineered Mouse Models, and using primary tumor Patient-Derived Xenografts, to investigate the efficacy of new drugs and new drug combinations. All of these genomic and genetic studies generate large volumes of data; thus, a significant portion of my lab is devoted to using genomic data and a systems biology approach to create computational predictors of complex cancer phenotypes.

Many diseases of the kidney remain poorly understood. My research program spans a range of disciplines (e.g., genetics, cell biology, immunology) and experimental approaches (e.g., microscopy, molecular biology, biochemistry, and model organisms—Drosophila and zebrafish) to answer fundamental questions regarding the genetic and cellular basis of kidney function and disease. We are also developing novel assays to study autoimmune diseases of the kidney, with the goal of facilitating patient diagnosis and treatment. By applying modern tools to long-standing problems, we hope to translate our research findings to improved patient outcomes.

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

We are interested in the links between epigenetics and gene regulation. Our primary focus is on understanding how changes to the composition of chromatin remodeling complexes are regulated, how their disruption affects their function, and contributes to disease. We focus on the SWI/SNF complex, which is mutated in 20% of all human tumors. This complex contains many variable subunits that can be assembled in combination to yield thousands of biochemically distinct complexes. We use a variety of computational and wet-lab techniques in cell culture and animal models to address these questions.

Keywords: genetic epidemiology, human genetics, genome-wide association studies, precision medicine, multi-omics, cardiovascular disease, inflammation, hematological traits

In my research program, I use human genomics and multi-omics to understand inherited and environmental risk factors for cardiometabolic diseases and related quantitative traits. I work to link genetic variants to function through integration with multi-omics data, including transcriptomic, methylation, proteomic, and metabolomic measures. This work has important implications for cardiometabolic risk prediction across diverse populations and improved understanding of disease biology. A focus on understudied African American and Hispanic/Latino populations is a central theme of my research; human genetics research is dramatically unrepresentative of global populations, with ~95% of genome-wide association study participants of European or East Asian ancestry. As complex trait genetics moves into the clinic, increasing diversity is essential to ensure that all populations benefit from the promise of precision medicine.

I play a leadership role in collaborative efforts in human genetics, for example serving as a Genetics Working Group co-chair for the Jackson Heart Study (JHS), one of the largest population based studies of African Americans, and an Inflammation/Hematology working group co-chair for the Population Architecture Using Genomics and Epidemiology (PAGE) consortium. I am also a co-convener of the Multi-Omics working group for the NHLBI Trans-Omics for Precision Medicine (TOPMed) program.

The end joining pathway is a major means for repairing chromosome breaks in vertebrates.  My lab is using cellular and cell-free models to learn how end joining works, and what happens when it doesn’t.

Heart failure is an increasingly prevalent cause of death world-wide, but the genetic and epigenetic underpinnings of this disease remain poorly understood. Our laboratory is interested in combining in vitro, in vivo and computational techniques to identify novel markers and predictors of a failing heart. In particular, we leverage mouse populations to perform systems-level analyses with a focus on co-expression network modeling and DNA methylation, following up in primary cell culture and CRISPR-engineered mouse lines to validate our candidate genes and identify potential molecular mechanisms of disease progression and amelioration.

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.

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.

Our long term goals are to better define mechanisms of chronic intestinal inflammation and to identify areas for therapeutic intervention. Research in our laboratories is in the following four general areas: 1) Induction and perpetuation of chronic intestinal and extraintestinal inflammation by resident intestinal bacteria and their cell wall polymers, 2) Mechanisms of genetically determined host susceptibility to bacterial product,. 3) Regulation of immunosuppressive molecules in intestinal epithelial cells and 4) Performing clinical trials of novel therapeutic agents in inflammatory bowel disease patients.

Pain is a complex experience with sensory and emotional components. While acute pain is essential for survival, chronic pain is a debilitating disease accompanied by persistent unpleasant emotions. Efficient medications against chronic pain are lacking, and the absence of alternative to opioid analgesics has triggered the current Opioid Epidemic. Our lab studies how our nervous system generates pain perception, at the genetic, molecular, cellular, neural circuit, and behavioral levels. We also seek to understand how opioids alter activity in neural circuits to produce analgesia, but also side effects such as tolerance, addiction and respiratory depression. To this aim, we investigate the localization, trafficking and signaling properties of opioid receptors in neurons. These studies clarify pain and opioid mechanisms for identifying novel non-addictive drug targets to treat pain and strategies to dissociate opioid analgesia from deleterious effects.

I am a surgeon-scientist specialized in head and neck cancers. My goal is to address translationalquestions with genomic data and bioinformatic methods, as well as benchtop experimentation. My clinical practice as a head and neck cancer surgeon also influences my research by helping me seek solutions to problems that will directly inform gaps in the current treatment protocols.

I have developed a strong interest in HPV genomics as well as HPV/host genome integrations, as these factors are intrinsically related to transcriptional diversity and patient outcomes in HPV-associated head and neck cancers. Our work has helped to demonstrate that a novel mechanism of HPV-mediated oncogenesis requiring NF-kB activation is present in nearly 50% of oropharyngeal tumors. In this vein, we are aggressively investigating the cellular interplay between the NF-kB pathway and persistent HPV infection, tumor radiation response, NRF2 signaling, and more.

Another outgrowth of this work has been investigating APOBEC3B and its non-canonical roles in regulating transcription. Our preliminary work has demonstrated that APOBEC3B has surprisingly strong transcriptional effects in HPV+ HNSCC cells and may promote oncogenesis and tumor maintenance by suppressing the innate immune response and influencing the HPV viral lifecycle.

Our group also have a strong interest in translational genomic studies. Our group is working to develop methods that will make gene expression-based biomarkers more successful in the clinic, as well as studying many aspects of genomic alterations that contribute to the development of squamous cell carcinomas.

The Schrider Lab develops and applies computational tools to use population genetic datasets to make inferences about evolutionary history. Our research areas include but are not limited to: characterizing the effects natural selection on genetic variation within species, identifying genes responsible for recent adaptation, detecting genomic copy number variants and other weird types of mutations, and adapting machine learning tools for application to questions in population genetics and evolution. Study organisms include humans, the fruit fly Drosophila melanogaster and its relatives, and the malaria vector mosquito Anopheles gambiae.

Genome instability is a major cause of cancer. We use the model organism Drosophila melanogaster to study maintenance of genome stability, including DNA double-strand break repair, meiotic and mitotic recombination, and characterization of fragile sites in the genome.  Our primary approaches are genetic (forward and reverse, transmission and molecular), but we are also using biochemistry to study protein complexes of interest, genomics to identify fragile sites and understand the regulation of meiotic recombination, fluorescence and electron microscopy for analysis of mutant phenotypes, and cell culture for experiments using RNA interference.

The Shiau Lab is integrating in vivo imaging, genetics, genome editing, functional genomics, bioinformatics, and cell biology to uncover and understand innate immune functions in development and disease. From single genes to individual cells to whole organism, we are using the vertebrate zebrafish model to reveal and connect mechanisms at multiple scales. Of particular interest are 1) the genetic regulation of macrophage activation to prevent inappropriate inflammatory and autoimmune conditions, and 2) how different tissue-resident macrophages impact vertebrate development and homeostasis particularly in the brain and gut, such as the role of microglia in brain development and animal behavior.

Our laboratory studies the coordination of histone-modifying enzymes in regulating chromatin structure, enhancer activation, and transcription. We utilize mouse genetics and cell culture model systems to study the mechanisms of enhancer activation in neural crest cell epigenetics, craniofacial development, and altered enhancer regulation in cancer. This is accomplished through a variety of techniques including mouse mutagenesis, fluorescent reporters to isolate primary cells of interest, low cell number genomics, and proteomic approaches.

We are interested in elucidating context-specific functions of products from single long noncoding RNA (lncRNA) loci. Since lncRNAs have been implicated in many cellular processes, it is critical to delineate specific roles for each lncRNA. Moreover, as they are increasingly associated with diseases including developmental disorders, degenerative diseases, and cancers, defining their functions will be an important precursor to their use as diagnostics and therapeutics. We specialize in adopting -omics approaches including genomics, transcriptomics and proteomics, combined with single molecule methods to study the intermolecular interactions – RNA-protein, RNA-RNA and RNA-chromatin that lncRNAs use to execute their functions in normal stem cells and cancer.

Our laboratory is examining the role of histone post-translational modifications in chromatin structure and function.  Using a combination of molecular biology, genetics and biochemistry, we are determining how a number of modifications to the histone tails (e.g. acetylation, phosphorylation, methylation and ubiquitylation) contribute to the control of gene transcription, DNA repair and replication.

I study complex traits using linkage, association, and genetic epidemiological approaches.  Disorders include schizophrenia (etiology and pharmacogenetics), smoking behavior, and chronic fatigue.

First, we study the complex HIV-1 population that exists within a person.  We use this complexity to ask questions about viral evolution, transmission, compartmentalization, and pathogenesis.  Second, we are exploring the impact of drug resistance on viral fitness and identifying new drug targets in the viral protein processing pathway.  Third, we participate in a collaborative effort to develop an HIV-1 vaccine.  Fourth, we are using mutagenesis to determine the role of RNA secondary structure in viral replication.

The Tarantino lab studies addiction and anxiety-related behaviors in mouse models using forward genetic approaches. We are currently studying a chemically-induced mutation in a splice donor site that results in increased novelty- and cocaine-induced locomotor activity and prolonged stress response. We are using RNA-seq to identify splice variants in the brain that differ between mutant and wildtype animals. We are also using measures of initial sensitivity to cocaine in dozens of inbred mouse strains to understand the genetics, biology and pharmacokinetics of acute cocaine response and how initial sensitivity might be related to addiction. Finally, we have just started a project aimed at studying the effects of perinatal exposure to dietary deficiencies on anxiety, depression and stress behaviors in adult offspring. This study utilizes RNA-seq and a unique breeding design to identify parent of origin effects on behavior and gene expression in response to perinatal diet.

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.

We aim to dissect the epigenetic and transcriptional mechanisms that shape T cell lineage specification during development in the thymus and in the periphery upon antigen (microbial, viral) encounter. Aberrant expression of transcription and epigenetic factors can result in inflammation, autoimmunity or cancer. We are using gene deficient mouse models, multiparameter Flow Cytometry, molecular biology assays and next generation sequencing technologies to elucidate the regulatory information in cells of interest (transcriptome, epigenome, transcription factor occupancy).

We are a quantitative genetics lab interested the relationship between genes and complex disease. Most of our work focuses on developing statistical and computational techniques for the design and analysis of genetic experiments in animal models. This includes, for example: Bayesian hierarchical modeling of gene by drug effects in crosses of inbred mouse strains; statistical methods for identifying quantitative trait loci (QTL) in a variety of experimental mouse populations (including the Collaborative Cross); computational methods for optimal design of studies on parent of origin effects; modeling of diet by gene by parentage interactions that affecting psychiatric disease; detection and estimation of genetic effects on phenotypic variability. For more information, visit the lab website.

My research interests are focused on understanding the effects of genetic and environmental factors and their interaction on complex human diseases using a combination of statistical, molecular and bioinformatics approaches. My specific interests include understanding the influence of genetic variants on serum uric acid levels (a biomarker for renal-cardiovascular disease), effect of gene by diet interactions on serum uric acid levels and associated renal-cardiovascular disease risk factors and identification of functional variants affecting these disorders that will lead to novel treatment options.

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).

How the loss of different components of the SWI/SNF complex contributes to neoplastic transformation remains an open and important question. My laboratory concentrates on addressing this question by the combined use of biological, biochemical and mouse models for SWI/SNF complex function.

My lab concentrates on studying the molecular genetic basis of the evolutionary processes of adaptation and speciation. The questions we ask are what are the sequence changes that lead to variation between species and diversity within species, and what can these changes tell us about the processes that lead to their evolution. We use a number of different techniques to answer these questions, including molecular biology, sequence analyses (i.e. population genetics and molecular evolution techniques), physiological studies, and examinations of whole-organism fitness. Currently work in the lab has focused on a intertidal copepod species that is an excellent model for the initial stages of speciation (and also provides opportunities to study how populations of this species adapt to their physical environment).

Interest areas: Developmental Biology, Cell Biology, Cancer Biology, Stem Cells, Genetics

PhD programs: Pathobiology & Translational Sciences, Genetics & Molecular Biology, Cell Biology & Physiology, Oral Biology, Biology

Tissue development and homeostasis depend on the precise coordination of self-renewal and differentiation programs. A critical point of regulation of this balance is at the level of cell division. In the Williams lab, we are interested in stratified epithelial development, stem cells, and cancer, with a particular interest in how oriented cell divisions contribute to these processes. Asymmetric cell divisions maintain a stable pool of stem cells that can be used to sustain tissue growth, or mobilized in response to injury. However, dysregulation of this machinery can lead to cancer, particularly in epithelia where tissue turnover is rapid and continuous. Using the mouse epidermis and oral epithelia as model systems, we utilize cell biological, developmental and genetic approaches to study the molecular control of oriented cell divisions and mitotic spindle positioning, and how division orientation impacts cell fate choices in development, homeostasis, injury, and disease.

Our lab uses human genetics to identify new mechanisms driving coronary artery disease (CAD). Starting with findings from genome-wide association studies (GWAS) of CAD, we identify the causal gene at a given locus, study the effect of this gene on cellular and vessel wall biology, and finally determine the molecular pathways by which this gene influences CAD risk. Within this framework, we use complex genetic mouse models and human vascular samples, single-cell transcriptomics/epigenomics and high-throughput CRISPR perturbations, as well as traditional molecular biology techniques.

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.

We try to bridge the gap between genetic risk factors for psychiatric illnesses and neurobiological mechanisms by decoding the regulatory relationships of the non-coding genome. In particular, we implement Hi-C, a genome-wide chromosome conformation capture technique to identify the folding principle of the genome in human brain. We then leverage this information to identify the functional impacts of the common variants associated with neuropsychiatric disorders.

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

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.

My research has been concentrated on the areas of statistical genetics and genomics to investigate the role of genetic variations on complex quantitative traits and diseases. I work primarily in the development, as well as the examination of statistical properties, of theoretical methodologies appropriate for the interpretation of genetic data.

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