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.

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?

We are interested in determining the mechanisms involved in the beneficial modulation of the gut microbiota by prebiotics (functional foods that stimulate growth of gut native beneficial bacteria) and probiotics (live bacteria that benefit their host). Specifically, we aim to develop prebiotic and probiotic interventions as alternatives to traditional treatments for microbiota-health related conditions, and to advance microbiota-based health surveillance methods.

Our lab is interested in the mechanisms of membrane trafficking in eukaryotic cells. Using a combination of biochemistry, in vitro reconstitution, and structural biology, we seek to understand how protein complexes assemble to bend and perturb membranes during vesicle budding (endocytosis) and vesicle fusion (exocytosis). Our group also specializes in cryo-electron microscopy (cryo-EM) and we use semi-native substrates (nanodiscs, liposomes) to visualize complexes engaged with the membrane.

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.

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 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.

The immune system of severely burned patients becomes extremely suppressed after injury. An overwhelming number of patients die from wound infection and sepsis. However, we are unable to graft these patients with skin from other donors as their immune system is still able to reject the graft efficiently. Our inability to cover the wound site leaves the patients further open to bacterial and fungal infections. Our laboratory investigates the translational immune mechanisms for these devastating consequences of burn within mouse models and burn patients. Focuses in the lab include 1) investigation of innate molecule control of both the innate and adaptive immune systems after burn injury, 2) Role of innate signaling to Damage Associated Molecular Patterns in Immune Dysfunction after burn / inhalational injury,focusing on mTOR-mediated Immunomodulation 3) Using NRF2/KEAP1-Targeted Therapy to Prevent Pneumonitis and Immune Dysfunction After Radiation or Combined Burn-Radiation Injury and 4) Investigating sex-specific disparities in Immune Dysfunction after trauma / transplantation. ​

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.

Molecular evolution and mechanistic enzymology find powerful synergy in our study of aminoacyl-tRNA synthetases, which translate the genetic code. Class I Tryptophanyl-tRNA Synthetase stores free energy as conformational strain imposed by long-range, interactions on the minimal catalytic domain (MCD) when it binds ATP. We study how this allostery works using X-ray crystallography, bioinformatics, molecular dynamics, enzyme kinetics, and thermodynamics. As coding sequences for class I and II MCDs have significant complementarity, we also pursuing their sense/antisense ancestry. 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 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.

The Chung lab is engineering immune cells, particularly T cells, to achieve maximum therapeutic efficacy at the right place and timing. We explore the crossroads of synthetic biology, immunology, and cancer biology. Particularly, we are employing protein engineering, next-gen sequencing, CRISPR screening, and bioinformatics to achieve our objectives:

(1) Combinatorial recipes of transcription factors for T cell programming.

(2) Technologies for temporal regulation and/or rewiring of tumor and immune signal activation (chemokine, nuclear, inhibitor receptors).

(3) Synthetic oncolytic virus for engineering tumor-T cell crosstalk.

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

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.

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.

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.

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.

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.

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.

My lab studies how genes function within the three-dimensional context of the nucleus to control development and prevent disease. We combine genomic approaches (ChIP-Seq, ChIA-PET) and genome editing tools (CRISPR) to study the epigenetic mechanisms by which transcriptional regulatory elements control gene expression in embryonic stem cells.  Our current research efforts are divided into 3 areas: 1) Mapping the folding pattern of the genome 2) Dynamics of three-dimensional genome organization as cells differentiate and 3) Functional analysis of altered chromosome structure in cancer and other diseases.

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.

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.

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

The Furey Lab is interested in understanding gene regulation processes in specific cell types, especially with respect to complex phenotypes, and the effect of genetic and environmental variation on gene regulation. We have explored these computationally by concentrating on the analysis of genome-wide open chromatin data generated from high-throughput sequencing experiments; and the development of statistical methods and computational tools to investigate underlying genetic and biological mechanisms of complex phenotypes. Our current projects include determining the molecular effects of exposure to ozone on chromatin, gene regulation, and gene expression in alveolar (lung) macrophages of genetically diverse mouse strains. We are also exploring genetics, chromatin, transcriptional, and microbial changes in inflammatory bowel diseases to identify biomarkers of disease onset, severity, and progression.

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.

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.

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 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.

We are interested in basic DNA-protein interactions as related to – DNA replication, DNA repair and telomere function.  We utilize a combination of state of the art molecular and biochemical methods together with high resolution electron microscopes.

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.

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

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.

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.

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.

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

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 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.

The Jacox Lab aims to improve patient care and outcomes in oral health. This goal takes shape via several tracks of interdisciplinary human studies:

-A primary focus of the lab has been on outcomes of jaw surgery patients, who suffer from Dentofacial Disharmonies (DFD). Patients with DFD have severe skeletal disproportions with underbites or open bites, necessitating orthodontics and jaw surgery for full correction. Roughly 80% of our patients with DFD exhibit speech distortions, compared to 5% of the general population, which negatively impact their self-confidence and quality of life. Despite patients pursuing invasive surgery, it is unknown whether jaw surgery is palliative for articulation errors. We are using ultrasound, audio and video imaging to explore the mechanism of articulation errors among patients with DFD. Furthermore, our lab is conducting a longitudinal study of DFD patients to determine if jaw surgery improves speech distortions, in collaboration with oral surgeons, linguistics and speech pathology.

-An additional focus of our lab has been studying use of Animal Assisted Therapy for management of anxiety and pain in dentistry. Dental anxiety effects 21-50% of patients and is associated with poor long-term oral health outcomes and need for urgent care due to dental avoidance. Non-pharmacological behavior interventions like dog therapy holds promise for reducing pain and anxiety perception for patients, and therefore improving dental experiences and promoting improved health outcomes. The lab is conducting a randomized controlled trial to evaluate best practices for canine therapy in pediatric dentistry, in collaboration with pediatric dentists, a psychology professor whose expertise is anxiety, and the UNC Biobehavioral Lab.

-As part of the COVID-19 research response, we are studying FDA-approved antiseptic mouth rinses for their ability to limit salivary viral infectivity to reduce risk of SARS-CoV-2 transmission. If an oral rinse is found to be efficacious at inactivating the SARS-CoV-2 virus, it could be a valuable preventative measure in settings where masks are removed, such as dental care, social settings, eating out, or work presentations. This study is conducted in collaboration with leading virologists and infectious disease experts at UNC.

Our lab uses cell culture and animal models to define the mechanisms that lead to heart failure and to identify novel approaches to its treatment.  We are particularly interested in the roles of inflammation and cardiomyocyte metabolism in the pathobiology of the failing heart. Ongoing projects focus on (1) the cardioprotective role of the alpha-1A adrenergic receptor; (2) transcriptional regulation by the nuclear receptor ROR-alpha; (3) cardiotoxicity of antineoplastic kinase inhibitors.

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.

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.

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.

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.

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

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.

The Laederach Lab is interested in better understanding the relationship between RNA structure and folding and human disease. We use a combination of computational and experimental approaches to study the process of RNA folding and in the cells. In particular, we develop novel approaches to analyze and interpret chemical and enzymatic mapping data on a genomic scale. We aim to fundamentally understand the role of RNA structure in controlling post-transcriptional regulatory mechanisms, and to interpret structure as a secondary layer of information (http://www.nature.com/nature/journal/v505/n7485/full/505621a.html).  We are particularly interested in how human genetic variation affects RNA regulatory structure. We investigate the relationship between disease-associated Single Nucleotide Polymorphisms occurring in Human UTRs and their effect on RNA structure to determine if they form a RiboSNitch.

We use molecular virology approaches and mouse models of infection to understand innate immune mechanisms that control arbovirus pathogenesis (e.g. West Nile, Zika, and La Crosse viruses). Bat flaviviruses have unusual vector/host relationships; understanding the viral and host factors that determine flavivirus host range is important for recognizing potential emerging infections. We are studying the antiviral effects of interferon lambda (IFN-λ) at barrier surfaces, including the blood-brain barrier and the skin. We also use mouse models of atopic dermatitis and herpes simplex virus infection to understand the effects of IFN- λ in the skin.

Our research focuses on the discovery and design of new gene-encoded bioactive small molecules from bacteria.  We are interested in understanding enzymes involved in their biosynthesis, their therapeutic mechanisms of action, and implications in health and diseases, in particular with respect to the human microbiome.  This work is driven by intensive development of new metabolomics and genomics technologies.  We subsequently manipulate and engineer these biosynthetic pathways to make new and improved molecules as potential therapeutics such as antibiotics.

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.

The overall goal of our research is to develop an enzyme-based approach to synthesize heparin- and heparan sulfate-like therapeutics.  The lab is currently focusing on improving the anticoagulant efficacy of heparin drug as well as synthesizing heparin-like compounds that inhibit herpes simplex virus infections.  We are also interested in using protein and metabolic engineering approaches for preparing polysaccharides with unique biological functions.

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.

My research goals are to identify the mechanisms by which environmental factors regulate smooth muscle cell phenotype and to define the transcriptional pathways that regulate SMC-specific gene expression.

The 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 overall goal of our laboratory is to obtain new insights into the host-virus interaction, particularly in HIV infection, and translate discoveries in molecular biology and virology to the clinic to aid in the treatment of HIV infection. A subpopulation of HIV-infected lymphocytes is able to avoid viral or immune cytolysis and return to the resting state. Current work focuses on the molecular mechanisms that control the latent reservoir of HIV infection within resting T cells. We have found that cellular transcription factors widely distributed in lymphocytes can remodel chromatin and maintain quiescence of the HIV genome in resting CD4+ lymphocytes. These studies give insight into the basic molecular mechanisms of eukaryotic gene expression, as well as new therapeutic approaches for HIV infection.

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 McGinty lab uses structural biology, protein chemistry, biochemistry, and proteomics to study epigenetic signaling through chromatin in health and disease. Chromatin displays an extraordinary diversity of chemical modifications that choreograph gene expression, DNA replication, and DNA repair – misregeulation of which leads to human diseases, especially cancer. We prepare designer chromatin containing specific combinations of histone post-translational modifications. When paired with X-ray crystallography and cryo-electron microscopy, this allows us to interrogate mechanisms underlying epigenetic signaling at atomic resolution.

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.

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.

Our lab seeks to better understand the maturation and regulation of a group of human lipases.  We aim to uncover how these lipases properly fold and exit the ER, and how their activity is subsequently regulated.  We study the membrane-bound and secreted proteins that play a role in lipase regulation.  Our research can potentially impact human health as biochemical deficiencies in lipase activity can cause hypertriglyceridemia and associated disorders, such as diabetes and atherosclerosis.  We are an interdisciplinary lab and aim to address these questions using a variety of techniques, including membrane protein biochemistry, enzymology, and structural and molecular biology.

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

My research interests include the role of von Willebrand factor in thrombosis and atherosclerosis. Our current lab work focuses on the molecular biology of porcine von Willebrand factor.

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.

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 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.

It is estimated that less than 2% of the human genome codes for a functional protein.  Scattered throughout the rest of the genome are regulatory regions that can exert control over genes hundreds of thousands of base pairs away through the formation of DNA loops.  These loops regulate virtually all biological functions but play an especially critical role in cellular differentiation and human development. While this phenomenon has been known for thirty years or more, only a handful of such loops have been functionally characterized.  In our lab we use a combination of cutting edge genomics (in situ Hi-C, ATAC-seq, ChIP-seq), proteomics, genome editing (CRISPR/Cas), and bioinformatics to characterize and functionally interrogate dynamic DNA looping during monocyte differentiation.  We study this process both in both healthy cells and in the context of rheumatoid arthritis and our findings have broad implications for both cell biology as well as the diagnosis and treatment of human disease.

My lab is driven to understand the neuronal pathologies underlying neurodevelopmental disorders, and to use this information to identify novel therapeutics.  We focus our research on monogenic autism spectrum disorders, including Angelman, Rett, and Pitt-Hopkins syndromes.  We employ a diverse number of techniques including: electrophysiology, molecular biology, biochemistry, mouse engineering, and in vivo imaging.

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

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.

Our research is focused on RNA-binding proteins and their physiopathological roles. An understudied aspect of human disease is gene regulation by modulation of mRNA function. In our research lab we investigate functional connections between the RNA-binding protein Zinc Finger Protein 36 Like-2 (ZFP36L2 or L2) and human diseases. L2 is a member of the Tris-Tetra-Proline or Zinc Finger Protein 36 (TTP/ZFP36) family of RNA-binding proteins that bind Adenine-uridine-Rich Elements (AREs) in the 3’ untranslated regions of target mRNAs. Upon binding, L2 accelerates mRNA target degradation and/or inhibits mRNA translation, ultimately decreasing the protein encoded by the L2-target mRNA.

We have three particular goals:

• Determine new specific L2-mRNA targets involved in human diseases.
• Determine the mechanism(s) by which L2 modulates these novel RNA targets.
• Determine the physiological consequences of L2 ablation in specific cells types using mouse models and CRISPR/Cas9-mediated knockout system.

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.

We are interested in unraveling the molecular basis for human disease and discover new treatments focused on human and microbial targets. Our work extends from atomic-level studies using structural biology, through chemical biology efforts to identify new drugs, and into cellular, animal and clinical investigations. While we are currently focused on the gut microbiome, past work has examined how drugs are detected and degraded in humans, proteins designed to protect soldiers from chemical weapons, how antibiotic resistance spreads, and novel approaches to treat bacterial infections. The Redinbo Laboratory actively works to increase equity and inclusion in our lab, in science, and in the world. Our lab is centered around collaboration, open communication, and trust. We welcome and support anyone regardless of race, disability, gender identification, sexual orientation, age, financial background, or religion. We aim to: 1) Provide an inclusive, equitable, and encouraging work environment 2) Actively broaden representation in STEM to correct historical opportunity imbalances 3) Respect and support each individual’s needs, decisions, and career goals 4) Celebrate our differences and use them to discover new ways of thinking and to better our science and our community

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.

Our lab uses a systems biology approach to study phenotypic heterogeneity in bacteria. We develop tools that quantify single cell bacterial transcription. We then compare dynamic measurements during vegetative growth and infection to identify regulators of gene expression and mechanisms that bacteria use to coordinate community organization. With this data we want to understand the role of heterogeneity and noise in infectious disease.

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.

We have three main areas of research focus: (1) Nucleotide excision repair: The only known mechanism for the removal of bulky DNA adducts in humans. (2) DNA damage checkpoints:  Biochemical pathways that transiently block cell cycle progression while DNA contains damage.  (3) Circadian rhythm:  The oscillations in biochemical, physiological and behavioral processes that occur with the periodicity of about 24 hours.

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.

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.

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 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.

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.

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

The 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.

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).

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

We want to understand why common pediatric respiratory virus infections cause severe disease in some people. Currently we focus on enterovirus D68, which typically causes colds but rarely causes acute flaccid myelitis, a polio-like paralyzing illness in children. We study both the pathogen and the host immune response, as both can contribute to pathogenesis. Projects focus on use of reverse genetic systems to create reporter viruses to infect both human respiratory epithelial cultures and small animal models such as mice. Human monoclonal antibody effects on pathogenesis are also of interest.

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).

With an emphasis on chromatin biology and cancer epigenetics, our group focuses on mechanistic understandings of how chemical modifications of chromatin define distinct patterns of human genome, control gene expression, and regulate cell proliferation versus differentiation during development, and how their deregulations lead to oncogenesis. Multiple on-going projects employ modern biological technologies to: 1) biochemically isolate and characterize novel factors that bind to histone methylation on chromatin, 2) examine the role of epigenetic factors (chromatin-modifying enzymes and chromatin-associated factors) during development and tumorigenesis using mouse knockout models, 3) analyze epigenomic and transcriptome alternation in cancer versus normal cells utilizing next-generation sequencing technologies, 4) identify novel oncogenic or tumor suppressor genes associated with leukemia and lymphoma using shRNA library-based screening. We are also working together with UNC Center of Drug Discovery to develop small-molecule inhibitors for chromatin-associated factors as novel targeted cancer therapies.

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.

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.

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.

We are a translational cancer research lab. The overall goal of our research is to find therapeutic targets and biomarkers for patients with pancreatic cancer and to translate our results to the clinic. In order to accomplish this, we analyze patient tumors using a combination of genomics and proteomics to study the patient tumor and tumor microenvironment, identify and validate targets using forward and reverse genetic approaches in both patient-derived cell lines and mouse models. At the same time, we evaluate novel therapeutics for promising targets in mouse models in order to better predict clinical response in humans.

Psychosocial stress is abundant in modern societies and, when chronic or excessive, can have detrimental effects on our bodies. But how exactly does stress “get under the skin?” Our lab examines how stress shapes the human epigenome as age advances. Epigenetic changes are a set of chemical modifications that regulate gene transcription without altering the genetic code itself. We examine how lasting epigenetic patterns result from stressful experiences, accrue throughout life, and can in turn shape health or disease trajectories. We address these questions through a translational approach that combines large-scale analyses in human cohorts with mechanistic work in cellular models. We use both bioinformatics and wet lab tools. Our passion is to promote creative team work, offer strong mentorship, and foster scientific growth.

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.