BBSP Faculty

The broad goal of our research is to understand basic mechanisms regulating erythropoiesis (red blood cell differentiation and maturation). Our current work focuses on a family of dual functional proteins (poly C binding proteins) which both regulate RNA processing and chaperone iron within cells. Using biochemical, cellular, and in vivo models we explore the cross talk between iron trafficking and RNA regulation mediated by poly C binding proteins and how these activities are modulated by disease.

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?

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

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.

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.

Building a functioning brain requires an elaborate network of interactions between neurons and glia. We use mouse genetics, primary cell culture, quantitative proteomics, molecular biology, and super resolution microscopy to study glial cells during brain development. We are particularly interested in how astrocytes acquire their complex morphology and communicate with neighboring astrocytes, neurons, and oligodendrocytes. Furthermore, we are investigating how glial dysfunction drives the pathogenesis of brain disorders such as autism, schizophrenia, and leukodystrophy.

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.

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

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

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.

We are studying tissue integrity and repair to develop innovative approaches for regenerative medicine and cancer prevention. We concentrate on highly regenerative (endometrial and intestinal) tissues and are particularly interested in how persistent inflammation influences the breakdown of biochemical pathways that oversee genome stability, stem cell plasticity, and cell adhesions and how these events influence future tissue repair and onset of disease, such as cancer. Projects employ a variety of molecular, cellular, biochemical, genetic, and machine learning techniques that span across cell culture systems, genetically engineered mouse models, and human tissues to understand the impact of acute and chronic inflammation on cell division, cytoskeletal dynamics, and DNA repair in regenerating epithelial cells.

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.

My research lab focuses on the molecular pathogenesis of endometrial cancer, the most common gynecologic cancer in the Western world. Current projects include developing molecular diagnostics for predicting endometrial cancer histotype, stage, and recurrence; developing clinical and lab-based algorithms for the identification of patients with hereditary endometrial cancer (Lynch Syndrome); discovering novel molecular mediators of endometrial cancer invasion and metastasis; identifying signaling pathways important in the pathogenesis of endometrial cancer; and identifying molecular determinants of health disparities in endometrial cancer.

We study the molecular mechanisms of HIV latency. Transcriptional silencing of HIV is a key mechanism of persistence in patients, and is a barrier to viral eradication, but little is known about the latent reservoir or the molecular mechanisms that regulate it. As such, our repertoire of drugs for targeting latently infected cells is limited. Some latency reversing agents (LRAs) have been developed, but these are typically reactivate only a minor subset of proviruses. This inefficiency is in part due to the reservoir not constituting a uniform target, but instead being a heterogeneous set of cells with diverse characteristics and restrictions to HIV expression. However, most analyses of latency use bulk cell cultures assays in which crucial information about the behavior of individual cells is lost. Also, latently infected cells in patient samples are exceedingly rare, making them very difficult to study directly. New technological breakthroughs in the field of single cell analysis as well as the development of primary cell models for HIV latency now open the possibility of observing how latently infected cells form and are maintained at single cell resolution. Our lab has developed tools to study the establishment, maintenance and reversal of HIV latency at single cell resolution using multi-omics methods. Furthermore, we combine these approaches with genetic perturbation, time-lapse microscopy and novel bioengineering tools to gain insight into how the host cell regulates HIV latency. We have recently discovered using single cell RNAseq (scRNAseq) that latency in primary CD4 T cells is associated with expression of a distinct transcriptional signature (Bradley et al 2018). Our hypothesis is that this signature represents part of a cellular program that regulates latency, and that this program is an exciting novel target for the development of LRAs. Ongoing projects in the lab involve the application of new technologies to our model systems, and testing/validation of the roles of host cell pathways we have identified in HIV latency. Our overall goal is to identify new targets for the development of drugs to clear the HIV reservoir.

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

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.

Our laboratory now studies mechanisms of genome replication and pathogenesis of respiratory enteroviruses and evolution of neurovirulence using the tools of mechanistic enzymology, cell biology, stem-cell engineering, and virology. Our laboratory is also pioneering the development of tools to monitor viral infection dynamics on the single-cell level, aka “single-cell virology.”

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

We use cutting edge technology to study pathogenesis of human pulmonary diseases including cystic fibrosis, Job’s syndrome, idiopathic pulmonary fibrosis by both human specimens, mouse genetic models, with a goal of finding the therapies. Recently, we developed a serial of lung epithelial-lineage tracing systems, providing the powerful tools for identify mechanisms of lung disease involved in post-acute sequelae SARS-CoV-2 infection, also known as “long COVID”, in collaboration with Dr. Ralph Baric’s Lab at UNC-CH.

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.

Our goal is to understand the fundamental cell biology underlying processes such as neurodevelopment, angiogenesis, and the metastasis of cancer cells. Most of our experiments focus on molecular motors such as myosin-X and on the finger-like structures known as filopodia. We generally utilize advanced imaging techniques such as TIRF and single-molecule imaging in conjunction with mammalian cell culture. We also use molecular biology and biochemistry and are in the process of developing a mouse model to investigate the functions of myosin-X and filopodia. We are looking for experimentally driven students who have strong interests in understanding the molecular basis of dynamic cellular processes such as filopodial extension, mechanosensing, and cell migration.

We study proteases that induce rapid changes in cell morphology, behavior, and identity. We are particularly interested in ones that play a role in myotube formation, muscular dystrophies, rhabdomyosarcoma, and cachexia. Our model systems include C2C12 cells, primary myoblasts, patient-derived iPSCs, and zebrafish. In addition to standard cell biology approaches, we make use of chemical biology and advanced microscopy techniques. Ultimately, we seek to identify a combination of protease inhibitors/activators that can cure musculoskeletal diseases.

The long-term goal of my research is to incorporate ‘omic (genomic, epigenomic, proteomic, etc.) measurements into environmental human health hazard identification, prioritization and risk assessment using a quantitative and interpretable biological systems framework. Thus, short-term goals have been to develop the molecular tools to investigate key biological events, and measurable biomarkers linked to those events, related to important disease processes that are impacted by environmental chemical exposures, such as liver and lung toxicity.  We have focused recent efforts on early-in-life genomic and epigenetic alterations and linkages to latent adverse outcome susceptibility due to commons exposures, genetics, and pre-existing conditions. Our laboratory uses cutting edge techniques such as gene editing tools including CRISPR-based methods; next generation nucleic acid-based sequencing to probe the genome and epigenome; advance, high-throughput microscopy; targeted RNA, DNA, and non-coding RNA measurements such as digital drop PCR and Fireplex; and advanced in vitro models.

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

My research aims to uncover the molecular aspects of protein aggregation diseases (also called PAD) which include neurodegenerative diseases (such as Alzheimer’s disease and Amyotrophic Lateral Sclerosis), myofibrillar myopathies (such as muscular dystrophies), as well as the formation of age-related cataracts.  Although very distinct, these disorders share a common underlying pathogenic mechanism.  Using a combination of biochemistry and in vitro approaches, cell biology, and primary cells / transgenic mouse models, we will investigate the post-translational modifications (PTMs) that drive these disease processes. Ultimately, this research will provide a platform for future drug discovery efforts against these devastating diseases.

Lipids are crucial molecules for life. They play important roles in building membranes, storing energy, and cell signaling. We are interested in how lipids move around both within cells and between cells, for example from astrocytes to neurons. The lab uses cutting-edge microscopy techniques including live-cell imaging, superresolution microscopy, and multispectral imaging. We use these approaches to understand how defects in lipid trafficking contribute to metabolic and neurodegenerative diseases.

Dr. Corteselli’s research aims to uncover the mechanisms by which exposure to air pollutants causes lung injury. Her lab uses advanced in vitro models, including lung organoids and precision cut lung slices, to investigate the effects of inhaled toxicants on airway epithelial cell function, with a focus on redox homeostasis and signaling.

Our lab is interested in molecular mechanisms of oncogenesis, specifically as regulated by Ras and Rho family small GTPases. We are particularly interested in understanding how membrane targeting sequences of these proteins mediate both their subcellular localization and their interactions with regulators and effectors. Both Ras and Rho proteins are targeted to membranes by characteristic combinations of basic residues and lipids that may include the fatty acid palmitate as well as farnesyl and geranylgeranyl isoprenoids. The latter are targets for anticancer drugs; we are also investigating their unexpectedly complex mechanism of action. Finally, we are also studying how these small GTPases mediate cellular responses to ionizing radiation – how do cells choose whether to arrest, die or proliferate?

The Cyr laboratory studies cellular mechanisms for cystic fibrosis and prion disease. We seek to determine how protein misfolding leads to the lung pathology associated with Cystic Fibrosis and the neurodegeneration associated with prion disease.

Research in the Darville lab is focused on increasing our understanding of immune signaling pathways active in development of genital tract disease due to Chlamydia trachomatis and determination of chlamydial antigen-specific T cell responses that lead to protection from infection and disease. In vitro, murine model, and human studies are being performed with the ultimate goal to develop a vaccine against this prevalent sexually transmitted bacterial pathogen. Genetic and transcriptional microarray studies are being performed to explore pathogenic mechanisms and determine biomarkers of pelvic inflammatory disease due to Chlamydia as well as other sexually transmitted pathogens.

We study Borrelia burgdorferi (the agent of Lyme disease) as a model for understanding arthropod vector-borne disease transmission. We also study the epidemiology and pathogenesis of dengue viruses associated with hemorrhagic disease.

Our research centers on understanding the molecular basis of human carcinogenesis. In particular, a major focus of our studies is the Ras oncogene and Ras-mediated signal transduction. The goals of our studies include the delineation of the complex components of Ras signaling and the development of anti-Ras inhibitors for cancer treatment. Another major focus of our studies involves our validation of the involvement of Ras-related small GTPases (e.g., Ral, Rho) in cancer. We utilize a broad spectrum of technical approaches that include cell culture and mouse models, C. elegans, protein crystallography, microarray gene expression or proteomics analyses, and clinical trial analyses.

We study how mammalian cells regulate their survival and death (apoptosis). We have focused our work on identifying unique mechanisms by which these pathways are regulated in neurons, stem cells, and cancer cells. We utilize various techniques to examine this in primary cells as well as in transgenic and knock out mouse models in vivo. Our ultimate goal is to discover novel cell survival and death mediators that can be targeted for therapy in neurodegeneration and cancer.

A major focus of the Diekman lab is to develop new strategies to limit age-related osteoarthritis (OA).  The lab uses genetically-engineered mouse models to investigate the development of cellular senescence in joint tissues with physiologic aging.  One goal of this work is to determine whether “senolytic” compounds that induce selective apoptosis in senescent cells will mitigate OA development.  Our group has also developed genome-editing protocols for primary human chondrocytes to produce single-cell derived colonies with homozygous knockout of target genes.  We are using engineered tissues from these cells to dissect the mechanism of genes implicated in OA development by genome-wide association studies, as well as coupling these technologies to high throughput screening approaches for OA drug discovery.

We study host defense mechanisms in the lungs, particularly the inflammatory and innate immune processes important in the pathogenesis and course of bacterial pneumonia, acute lung injury/acute respiratory distress syndrome, and cigarette smoke-associated lung disease. Basic and translational studies address mechanisms of host defense, including recruitment and function of leukocytes, vascular permeability leading to edema, bacterial clearance and resolution.  Cell signaling pathways initiated by binding of leukocyte-endothelial cell adhesion molecules and molecular mechanisms underlying the functions of neutrophils are two particular areas.

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.

Our lab aims to identify the fundamental molecular mechanisms underlying heart development and congenital heart disease. Our multifaceted approach includes primary cardiac cell culture, genetic mouse models, biochemical/molecular studies, and transcriptomics. Additionally, we employ proteomics-based methods to investigate 1) protein expression dynamics, 2) protein interaction networks, and 3) post-translational modifications (PTMs) in heart development. Current research projects focus on investigating the function of two essential PTMs in cardiogenesis: protein prenylation and palmitoylation.

The Ehre laboratory studies the role of mucus in obstructive pulmonary diseases, such as asthma, and cystic fibrosis (CF), as well as in response to respiratory viruses (SARS-CoV-2 and RSV). Our research goal is to gain insights into the basic defects of airway mucus that lead to impaired mucociliary clearance and viral penetration. We use in vitro and in vivo models to study disease pathogenesis, test pharmacological agents and investigate how mucus obstruction and viral infection cause epithelial damage. In addition, we examine patient specimens to understand the role of inflammatory cytokines in disease severity. For these projects, we use integrative omics technologies (transcriptomics, digital spatial profiler, phenocycler) and high-resolution imaging (live, laser and scanning/transmission electron microscopy) to answer critical questions regarding mucus biology and airways response to inhaled pathogens and/or treatment.

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.

As the Director of the UNC Kidney Center, the scope of Dr. Falk’s research interests spans many disciplines, including molecular biology, immunology, genetics, pathology, cell biology, protein chemistry, epidemiology, pharmacokinetics and biostatistics. Dr. Falk is recognized world wide as a leader in research on kidney diseases related to autoimmune responses. He works closely with the basic research scientists within the UNC Kidney Center, including Dr. Gloria Preston, thus this research program provides an environment for Translational Research within the UNC Kidney Center.

Our lab studies the underlying structural and functional substrates of behavior in disease using rodent models. Specifically our goal is to develop a better understanding of how cellular function in the CNS is affected by drug-related substances (opioids, cannabinoids) in the context of HIV infection. That includes the study of how drugs of abuse exacerbate the pathogenesis of neuroAIDS but also the study of targets within the endocannabinoid system for the potential treatment of HIV. We use various in vivo and in vitro techniques, including primary cell culture models, behavioral conditioning tasks, live cell imaging, and electrophysiology.

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.

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

During development transcriptional and posttranscriptional networks are coordinately regulated to drive organ maturation, tissue formation, and cell fate. Interestingly, more than 90% of the human genes undergo alternative splicing, a posttranscriptional mechanism that explains how one gene can give rise to multiple protein isoforms. Heart and skeletal muscle are two of the tissues where the most tissue specific splicing takes place raising the question of how developmental stage- and tissue-specific splicing influence protein function and how this regulation occurs. In my lab we are interested on two exciting aspects of this broad question: i) how alternative splicing of trafficking and membrane remodeling genes contributes to muscle development, structure, and function, ii) the coupling between epigenetics and alternative splicing in postnatal heart development.

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

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 Good Laboratory is focused on the cellular and molecular mechanisms involved in the pathogenesis of a devastating intestinal disease primarily affecting premature infants called necrotizing enterocolitis (NEC). The long-term goal of the Good Lab is to understand the signaling pathways regulating the uncontrolled immune response in NEC and how these responses can be prevented through dietary modifications or targeted intestinal epithelial therapies. Her basic and translational research utilizes a bench-to-bedside approach with multiple cutting-edge techniques. In her pre-clinical studies, their team utilizes a humanized neonatal mouse model of NEC to understand the signaling pathways and immune cell responses involved in NEC development. Specifically, the laboratory interrogates ways to modulate the immune response, epithelial cell and stem cell regeneration as well as early microbial colonization during NEC. In the clinical component of her research program, Dr. Good leads a large multi-center NEC biorepository for the dedicated pursuit of molecular indicators of disease and to gain greater pathophysiologic insights during NEC in humans. Dr. Good also developed a premature infant intestine-on-a-chip model to study NEC and provide a personalized medicine approach to test new therapeutics. Her laboratory is currently funded with multiple NIH R01 grants and has previously received K08 and R03 funding as well as awards from the March of Dimes, the Gerber Foundation and the NEC Society.

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.

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.

The human placenta is the first organ to develop after fertilization and is the least studied! We hope to change this by using a multidisciplinary approach. From iPSC-derived trophoblasts in culture to mouse models and human placenta tissue, the Placental Cell Biology Group at NIEHS answers fundamental questions about placenta cell and developmental biology. Our lab uses a range of microscopy (cryo-EM, fluorescence), recombinant protein production, and -omics techniques. The goal of our research is to understand how autophagy controls placenta development, differentiation, and function.

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.

I am a Pediatric Pulmonologist. My lab studies cell phenotype regulation in the context of lung fibrosis and lung development. We use in vitro and ex vivo models, mouse models, human tissue, and multi-omic approaches to explore fibroblast phenotypes in the formation of lung alveoli and in the pathologic modeling of lung fibrosis, and explore novel therapies for lung disease.

Possible Rotation Projects:

Markers of mechanotransduction in lung alveolar formation (immunofluorescence, bioinformatics)
Biological aging of the lung (DNA methylation)
Precision cut lung slice culture to model fibrosis and test therapies ex vivo
Fibroblast phenotype regulation in transgenic mice
Fibroblast-epithelial interactions in lung organoids

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.

My research focus centers on retinal gene/drug therapy using nanotechnologies. My laboratory is interested in developing gene therapies for inherited blinding diseases and eye tumors. We are particularly interested in understanding the gene expression patterns that are regulated by the cis-regulatory elements. We utilize compacted DNA nanoparticles which have the ability to transfer large genetic messages to overcome various technical challenges and to appreciate the translational potential of this technology. This multidimensional technology also facilitated targeted drug delivery. Currently, we are working on the design and development of several specific nano formulations with targeting, bioimaging and controlled release specificities.

The Hathaway lab is focused on understanding the biological events responsible for dynamically regulating the selective expression of the mammalian genome. In multicellular organisms, genes must be regulated with high precision during stem cell differentiation to achieve normal development. Pathologically, the loss of proper gene regulation caused by defects in chromatin regulatory enzymes has been found to be a driving force in cancer initiation and progression. My lab uses a combination of chemical biology and cell biology approaches to unravel the molecular mechanisms that govern gene expression. We utilize new tools wielding an unprecedented level of temporal control to visualize changes in chromatin structure and function in mammalian cells and animal models. In addition, we seek to identify small molecule inhibitors that are selective for chromatin regulatory enzymes with the potential for future human therapeutics.

Our research focuses on understanding the molecular and cellular mechanisms of leukocyte (white blood cell) trafficking and homing in vascular inflammation and immune responses. We are interested in the glycobiology of the Selectin leukocyte adhesion molecules and their ligands, and understanding the roles for these glycoproteins in the pathogenesis of inflammatory/immune cardiovascular diseases such as atherosclerosis and vasculitis. We are also interested in the mechanisms whereby the selectins and their ligands link the inflammatory response and coagulation cascade and thereby modulate thrombosis and hemostasis.

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

The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has significantly elevated in the last years and continues to increase; however, despite the continuous rise of HPV-related OPSCC, molecular mechanisms of how HPV promotes OPSCC are not well defined. Our ongoing research projects focus on understanding the role of HPV in the development, maintenance, and progression of head and neck squamous cell carcinoma (HNSCC). These discoveries are leveraged to identify and test novel therapeutic strategies that exploit susceptibilities of HPV-associated HNSCC.

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

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

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

One of the main focuses of my work is the characterization of the large mucin gene products (Mr 2-3 million) and the complexes they make (Mr 10-100 million) essential for the formation of the mucus gels vital for epithelial protection and function. My current work is focused around the human lung, where there are many hypersecretory human diseases, including asthma, cystic fibrosis, and chronic bronchitis, in which these glycoconjugates are centrally implicated. Basic understanding of the qualitative and quantitative changes of mucin macromolecules in lung health and diseases is our main task.

Maintaining health and reducing disease-risk requires the brain to properly transduce signals across specialized regions and cell types. My lab studies neural signaling at the primary cilium, an antenna-like organelle that helps cells sense and respond to environmental cues. The function of primary cilia in the adult brain remains enigmatic. To probe cilia function, the lab will utilize mouse models, neural cultures, human brain samples, single-cell transcriptomics, proteomics, and microscopy. Ultimately, we aim to identify therapeutic targets for diseases like Alzheimer’s and Parkinson’s.

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.

Endothelial cells, which comprise the innermost wall of all blood vessels, are involved in a broad range of metabolic and cardiovascular diseases that represent a global challenge with high morbidity. Endothelial cell metabolism is an active process, and altered endothelial metabolism drive disease progression. The research in my lab focuses on the molecular mechanisms of endothelial cell metabolism and how they affect cardiovascular and metabolic diseases.

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

Living cells have been referred to as the test tubes of the 21st century. New bioactive reagents developed in our lab are designed to function in cells and living organisms. We have prepared enzyme inhibitors, sensors of biochemical pathways, chemically-altered proteins, and activators of gene expression. In addition, many of these agents possess the unique attribute of remaining under our control even after they enter the biological system. In particular, our compounds are designed to be inert until activated by light, thereby allowing us to control their activity at any point in time.

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

Congenital heart diseases are one of the most common birth defects in humans, and these arise from developmental defects during embryogenesis.  Many of these diseases have a genetic component, but they might also be affected by environmental factors such as mechanical forces. The Liu Lab combines genetics, molecular and cell biology to study cardiac development and function, focusing on the molecular mechanisms that link mechanical forces and genetic factors to the morphogenesis of the heart.  Our studies using zebrafish as a model system serve as the basic foundation to address the key questions in cardiac development and function, and could provide novel therapeutic interventions for cardiac diseases.

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

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

The Loeser lab uses a combination of in vitro studies in articular chondrocytes and in vivo studies in mice to examine molecular mechanisms of joint tissue destruction in aging and osteoarthritis. A major focus of this work is examining how reactive oxygen species regulate cell signaling through oxidation of Cys residues in specific kinases and phosphatases. Pathways of interest include integrin mediated signaling that stimulates matrix metalloproteinase (MMP) expression and IGF-I signaling that stimulates matrix production. Oxidative stress disrupts the balance in the activity of these pathways to favor matrix destruction over repair contributing to the development of osteoarthritis.

My research program is centered on understanding fundamental aspects of cell division. During cell division, complex DNA-protein interactions transform diffuse interphase chromatin into discrete mitotic chromosomes, condensing them several thousand fold to facilitate spatial segregation of sister chromatids. Concomitantly, kinetochores form specifically at centromere regions of chromosomes and regulate force-producing interactions with microtubules. While these processes are absolutely required for genomic stability, the in vivo mechanisms of chromosome and kinetochore assembly remain unsolved problems in biology. I investigate 1) the spatiotemporal regulation of mitotic chromosome assembly, and 2) the molecular basis of centromere specification. To do so, I will combine biochemical approaches with high-resolution light microscopy of live cells, whole organisms, and in vitro systems.

My research philosophy is summed up by a quote from Nobelist Albert Szent-Gyorgyi: “Discovery is to see what everybody has seen and to think what nobody has thought.” My lab studies the molecular and physical mechanisms of cell shape change during cytokinesis and tissue biogenesis during development. Specifically, we are defining how cells ensure proper alignment and sliding of cytoskeletal filaments, and determining the shape of the cell throughout division. To do so, we combine developmental biology, cell biology, biochemistry, and quantitative image analysis.

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

My research focuses on molecular mechanisms of mammalian nervous system development. We investigate mechanisms by which developing neurons migrate to the neocortex and form connections.

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.

Dr. Meeker’s research is focused on the mechanisms of HIV neuropathogenesis and the development of therapeutic strategies for the treatment of neuroinflammation. Inflammatory changes within the brain caused by the viral infection initiate a toxic cascade that disrupts normal neural function and can eventually lead to neuronal death. To explore the mechanisms responsible for this damage, we investigate changes in calcium homeostasis, glutamate receptor function and inflammatory responses in primary neuronal, microglial and macrophage cultures. New therapeutic approaches targeted to signal transduction pathways and calcium regulation that protect the neurons and reduce inflammation are under investigation.

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

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

How does a virus gain control over the host cell? My laboratory is interested in answering this question at the molecular level. By combining molecular biology and virology with new technologies (e.g. mass spectrometry, next generation sequencing), we investigate the mechanisms utilized by viruses to hijack infected cells. By understanding the specific function(s) of viral proteins during infection, we identify strategies used by viruses for deregulation of host cell processes. We use this information to characterize novel features of cell signaling pathways during infection, and to identify potential targets for anti-viral therapeutics.

We are interested in the physics of soft and squishy materials, especially the organization and mechanics of living cellular materials. We use theory and simulation in close collaboration with experiments to understand the complex structural and mechanical behavior of these systems. These questions and our approach to them are interdisciplinary and intersect several traditional fields, including cell biology, biophysics, fluid dynamics and applied mathematics.

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.

Modern Technologies from next-gen sequencing to high resolution imaging have advanced our knowledge of kidney development, function, and disease. We are among the pioneers utilizing techniques such as CHIP-seq, RNA-seq, modern genome editing, and imaging to understand how regulatory programs control progenitor populations during kidney development. Our goal is to understand how these programs contribute to progenitor specification and maintenance, and how they are altered during disease and aging. Our ultimate goal is translational applications of our research to develop new therapeutics and regenerative strategies.

We inhale about 10,000 L of air to take oxygen into our bodies every day. Along with the inhaled air, numerous pathogens, chemical pollutants, and other irritants are inhaled, which could pose potential life-threatening risks to our lungs. However, our lungs are protected by mucociliary clearance (MCC), a critical innate defense mechanism that is important for maintaining lung health. Okuda lab’s overall research interest focuses on how the MCC system is regulated to maintain homeostasis in the lung and how it fails in muco-obstructive lung diseases, including cystic fibrosis (CF), asthma, and COPD. Our previous work successfully characterized the regional expression patterns of major airway secretory mucins, MUC5AC/MUC5B, and CFTR/ionocytes in normal and CF human airways. These investigations provide insight into the small airway region (< 2 mm in diameter) as a critical site for pathogenesis of muco-obstructive lung diseases. We have developed a microdissection technique for human small airways and established in vitro and explant small airway epithelial cell cultures. We have combined these culture systems with single-cell-based omics approaches and gene editing technologies to understand cellular biology and physiology of the human small airways. In response to the emergent situation caused by SARS-CoV-2 pandemic, Okuda lab has been also actively involved in COVID-19 research.

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.

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.

We are a comprehensive, collaborative group with a primary focus on lead and early drug discovery for oncology and epigenetic targets and pathways. Our research applies reagent production, primary assay development, high-throughput screening, biophysics, and exploratory cell biology to enable small molecule drug discovery programs in solid partnership with collaborators, both within the Center for Integrative Chemical Biology and Drug Discovery and across the UNC campus. We apply small molecule hit discovery to highly validated biochemical targets as well as phenotypic cell-based assays. Our methods include various fluorescence-based readouts and high content microscopy. Examples of some of our collaborative small molecule discovery programs include, inhibition of chromatin methyl-lysine reader proteins, hit discovery for small GTPases such as K-Ras and Gaq, inhibitors of inositol phosphate kinases, inhibitors of protein-protein interactions involving CIB1 and MAGE proteins, and several cell-based efforts including a screen for compounds that enhance c-Myc degradation in pancreatic cancer cells. In addition, we are developing a DNA-encoded library approach for hit discovery to complement traditional high-throughput screening. Our ultimate goal is discovery of new chemical probes and medicines for exploratory biology and unmet medical needs, respectively.

Our lab develops computer-driven optical instrumentation for applications in biology and neurosciences, beyond traditional imaging systems. Our research is interdisciplinary and welcomes backgrounds in optical engineering, computer sciences, biology or neurosciences. Our primary goal is to develop optical brain-machine interfaces and other technologies that use advanced light sources and detectors to probe and manipulate cellular functions deep into tissue at depths where traditional microscopy tools can no longer retrieve images.

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 Polacheck Lab develops microfluidic and organ-on-chip technology for disease modeling and regenerative medicine. Our efforts are organized around three primary research thrusts: 1) Developing humanized microphysiological models for inherited and genetic disorders; 2) Defining the role of biofluid mechanics and hemodynamics on the cellular microenvironment; 3) Understanding the role of cell-cell adhesion in the generation and propagation of cellular forces during morphogenesis. We further work to translate the technology and techniques developed in our lab into tissue engineered therapies for organ replacement and regenerative medicine.

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.

The goal of my research is to define molecular mechanisms of immune cell co-option by cancer cells, with the hope of identifying novel targets for immune cell reprogramming. Central to our approach is analysis immune cell subtypes in KRas-driven models of pancreatic cancer. We use cell and animals models to study signals important for pro-tumorigenic activity of immune cells, as well as define role of physiologically relevant oncogenic mutations in driving these signals and enabling immune escape.

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.

My laboratory research is focused on basic cell biology questions as they apply to clinical lung disease problems. Our main work recently has been contributing to the Cystic Fibrosis (CF) Foundtation Stem Cell Consortium, with a focus on developing cell and gene editing therapies for CF. I contribute to UNC team science efforts on cystic fibrosis, aerodigestive cancers, emerging infectious diseases and inhalation toxicology hazards. I direct a highly respected tissue procurement and cell culture Core providing primary human lung cells and other resources locally, nationally and internationally. I co-direct the Respiratory Block in the UNC Translational Educational Curriculum for medical students and also teach in several graduate level courses.

Research in our lab is focused on understanding how cocaine abuse affects glial cell physiology, in particular neuron-astrocyte communication.  We utilize the rat cocaine self-administration/reinstatement model, which allows us to test hypotheses regarding not only how chronic cocaine use affects properties of astrocytes and the tripartite synapse, but also how compounds affecting glial cells may influence synaptic processing within the brain’s reward neurocircuitry and behavioral measures of drug seeking.

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

The research in our lab is centered on understanding the mechanisms and principles of movement at the cellular level. Cytoskeletal filaments – composed of actin and microtubules – serve as a structural scaffolding that gives cells the ability to divide, crawl, and change their shape.  Our lab uses a combination of cell biological, biochemical, functional genomic, and  high resolution imaging techniques to study cytoskeletal dynamics and how they contribute to cellular motion.

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.

Our lab examines cytoskeletal dynamics, the molecules that regulate it and the biological processes it is involved in using live cell imaging, in vitro reconstitution and x-ray crystallography.  Of particular interest are the microtubule +TIP proteins that dynamically localize to microtubule plus ends, communicate with the actin network, regulate microtubule dynamics, capture kinetochores and engage the cell cortex under polarity-based cues.

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 lab has two areas of interest: the molecular basis of liver diseases and the biochemical mechanisms of disorders linked to intermediate filament gene mutations. We use biochemical, cell-based and in vivo approaches to identify potential disease targets and to understand their function and regulation. The major goal of our work is to promote the discovery of pharmacological agents that can slow or halt the progression of these diseases.

Superfine’s group studies stimulus-responsive active and living materials from the scale of individual molecules to physiological tissues, including DNA, cells and microfluidic-based tissue models. We develop new techniques using advanced optical, scanning probe, and magnetic force microscopy. We pursue diverse physiological phenomena from cancer to immunology to mucus clearance in the lung. Our work includes developing systems that mimic biology, most recently in the form of engineered cilia arrays that mimic lung tissue while providing unique solutions in biomedical devices.

A critical component of airways innate defense is the thin liquid layer lining airway surfaces, the periciliary liquid (PCL), that provides a low viscosity solution for ciliary beating and acts a lubricant layer for mucus transport. Normal airways appear to be able to sense the PCL volume and adjust ion channel activity accordingly. The long term goal of this laboratory is to understand how homeostasis of PCL volume occurs in airway epithelia under normal and pathophysiological conditions. Currently, research in the Tarran lab is focused on three main areas: 1) Regulation of epithelial cell function by the extracellular environment, 2) Gender differences in cystic fibrosis lung disease and 3) The effects of cigarette smoke on epithelial airway ion transport. We utilize cell biological and biochemical techniques coupled with in vivo translational approaches to address these questions.

Local mRNA translation is critical for axon regeneration, synapse formation, and synaptic plasticity. While much of research has focused on local translation in dendrites and in peripheral axons, less is known about local translation in smaller diameter central axons due to the technical difficulty of accessing them. We developed microfluidic technology to allow access to axons, as well as nascent boutons and fully functional boutons. We identified multiple transcripts that are targeted to cortical and hippocampal axons in rat (Taylor et al. J Neurosci 2009). Importantly, this work countered the prevailing view that local mRNA translation does not occur in mature axons. We are actively investigating transcripts in axons that may play a role in establishing proper synaptic connections. We are also using our technology to identify transcripts targeted to axons and boutons in human neurons. These studies are a critical step towards the identification of key genes and signaling molecules during synapse development, axonal regeneration, and proper circuit function.

The Thaxton laboratory studies the intersection of stress and metabolism in immune cells for applications in cancer immunotherapy. Our pursuits center around the biology of the endoplasmic reticulum (ER). We aim to define how stress on the ER defines changes in protein homeostasis, metabolic fate, and antitumor efficacy of immune subsets in human tumors. In order to pursue our goals we collaborate vigorously with clinicians, creating a highly translational platform to expand our discoveries. Moreover, we design unique mouse models and use innovate technologies such as metabolic tracing, RNA-sequencing, and spectral flow cytometry to study how the stress of solid tumors impacts immune function. Ultimately, we aim to discover new ways to restore immune function in solid tumors to offer unique therapies for cancer patients.

Our broad long-term goal is to understand how mammalian cells maintain ordered control of DNA replication during normal passage through an unperturbed cell cycle, and in response to genotoxins (DNA-damaging agents).  DNA synthesis is a fundamental process for normal growth and development and accurate replication of DNA is crucial for maintenance of genomic stability.  Many cancers display defects in regulation of DNA synthesis and it is important to understand the molecular basis for aberrant DNA replication in tumors.  Moreover, since many chemotherapies specifically target cells in S-phase, a more detailed understanding of DNA replication could allow the rational design of novel cancer therapeutics.  Our lab focuses on three main aspects of DNA replication control:  (1) The S-phase checkpoint, (2) Trans-Lesion Synthesis (TLS) and (3) Re-replication.

The vertebrate retina is an extension of the central nervous system that controls visual signaling and circadian rhythm.  Our laboratory is interested in how the retina adapts to changing light intensities in the natural environment.  We are presently studying the regulation of 2 G protein-coupled receptor kinases, GRK1 and GRK7, that participate in signal termination in the light-detecting cells of the retina, the rods and cones.  Signal termination helps these cells recover from light exposure and adapt to continually changing light intensities.  Recently, we determined that GRK1 and GRK7 are phosphorylated by cAMP-dependent protein kinase (PKA).  Since cAMP levels are regulated by light in the retina, phosphorylation by PKA may be important in recovery and adaptation.  Biochemical and molecular approaches are used in 2 model organisms, mouse and zebrafish, to address the role of PKA in retina function. Keywords:  cAMP, cone, G protein-coupled receptor, GPCR, GRK, kinase, neurobiology, opsin, PKA, retina, rhodopsin rod, second messenger, signal transduction, vision.

Reproductive biology of early mammalian embryogenesis including gametogenesis, fertilization, and preimplantation embryo development. Effects of environmental disrupting chemicals on female reproductive tract development and function, with a focus on epigenetic alterations.

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.

My research focuses on signal transduction, proteins posttranslational modification, and protein/protein interaction under varieties of stress/disease conditions. One of my major research areas is vascular smooth muscle signal transduction under hyperglycemic and oxidative stress conditions. Most recently, regulation of vascular smooth muscle cells phenotypic switch under hyperglycemic/uremic conditions was funded by NIH. In addition, I investigate autoantigens that are responsible for autoimmune diseases, such as MCD/FSGS, which make the precise diagnosis and individualized treatment plan possible.

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.

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.