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.
Dr. Alexander works at the interface cancer genomics, clinical trials, and global pediatric oncology with three areas of research focus
1) Development and implementation of a novel genomic sequencing approaches for cancer diagnostics in low- and middle-income countries
2) Development, implementation, and de-implementation of diagnostic testing for genomic classification of pediatric cancer.
3) Investigation of new cancer therapeutics through early phase clinical trials for high-risk acute leukemia
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.
My research group is broadly interested in the application of sequencing technologies in medical genetics and genomics, using a combination of wet lab and computational approaches. As a clinician, I am actively involved in the care of patients with hereditary disorders, and the research questions that my group investigates have direct relevance to patient care. One project uses genome sequencing in families with likely hereditary cancer susceptibility in order to identify novel genes that may be involved in monogenic forms of cancer predisposition. Another major avenue of investigation examines the use of genome-scale sequencing in clinical medicine, ranging from diagnostic testing to newborn screening, to screening in healthy adults.
A growing body of work in the biomedical sciences generates and analyzes omics data; our lab’s work contributes to these efforts by focusing on the integration of different omics data types to bring mechanistic insights to the multi-scale nature of cellular processes. The focus of our research is on developing systems genomics approaches to study the impact of genomic variation on genome function. We have used this focus to study genetic and molecular variation in both natural and engineered cellular systems and approach these topics through the lens of computational biology, machine learning and advanced omics data integration. More specifically, we create methods to reveal functional relationships across genomics, transcriptomics, ribosome profiling, proteomics, structural genomics, metabolomics and phenotype variability data. Our integrative omics methods improve understanding of how cells achieve regulation at multiple scales of complexity and link to genetic and molecular variants that influence these processes. Ultimately, the goal of our research is advancing the analysis of high-throughput omics technologies to empower patient care and clinical trial selections. To this end, we are developing integrative methods to improve mutation panels by selecting more informative genetic and molecular biomarkers that match disease relevance.
Experimental Evolution of Viruses. We use both computational and experimental approaches to understand how viruses adapt to their host environment. Our research attempts to determine how genome complexity constrains adaptation, and how virus ecology and genetics interact to determine whether a virus will shift to utilizing new host. In addition, we are trying to develop a framework for predicting which virus genes will contribute to adaptation in particular ecological scenarios such as frequent co-infection of hosts by multiple virus strains. For more information, and for advice on applying to graduate school at UNC, check out my lab website www.unc.edu/~cburch/lab.
Our lab is trying to understand the mechanisms by which long noncoding RNAs orchestrate the epigenetic control of gene expression. Relevant examples of this type of gene regulation occur in the case of X-chromosome inactivation and autosomal imprinting. We specialize in genomics, but rely a combination of techniques — including genetics, proteomics, and molecular, cell and computational biology — to study these processes in both mouse and human stem and somatic cell systems.
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.
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 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.
We use the premier model plant species, Arabidopsis thaliana, and real world plant pathogens like the bacteria Pseudomonas syringae and the oomycete Hyaloperonospora parasitica to understand the molecular nature of the plant immune system, the diversity of pathogen virulence systems, and the evolutionary mechanisms that influence plant-pathogen interactions. All of our study organisms are sequenced, making the tools of genomics accessible.
With a particular interest in pediatric solid tumors, our lab aims to develop a mechanistic understanding of the role of aberrant or dysregulated transcription factors in oncogenesis.
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.
Our lab tries to understand viral pathogenesis. To do so, we work with two very different viruses – West Nile Virus (WNV) and Kaposi¹s sarcoma-associated herpesvirus (KSHV/HHV-8).
Dr. Divaris has diverse research interests and a portfolio interrogating both proximal and distal determinants of oral health and disease, ranging from genomics of oral health traits and behavioral sciences to health disparities and dental education. The core data-generating work is carried our via NIH grants U01-DE025046 (ZOE 2.0 study, “Genome-wide association study of early childhood caries”) and P01HD103133-02S2 (Pediatric HIV/AIDS Cohort Study (PHACS); Biofilm multi-omics in the AMPU UP cohort-research supplement). I am a pediatric dentist with doctoral and postdoctoral training in oral and genetic epidemiology and interests in biological determinants of oral health and disease.
We use an integrated approach (genomics, proteomics, computational biology) to study the molecular mechanisms of hormone and drug desensitization. Our current focus is on RGS proteins (regulators of G protein signaling) and post-translational modifications including ubiquitination and phosphorylation.
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.
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.
In the Ferris lab, we use genetically diverse mouse strains to better understand the role of genetic variation in immune responses to a variety of insults. We then study these variants mechanistically. We also develop genetic and genomic datasets and resources to better identify genetic features associated with these immunological differences.
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.
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.
My research interest is in genomic characterization and integrative genomic approaches to better understand cancer. My group is part of the NCI Genome Data Analysis Center focused on RNA expression analysis. We have a number of ongoing projects including developing molecular classifications for potential clinical utility, developing methods for deconvolution to understand bulk tissue heterogeneity, analysis of driver negative cancers, and analysis of ancestry markers with cancer features.
The lab focus is to understand the mechanism of gene-environment interactions by examining the genetic basis of epigenetic response to nutrition and environmental toxicants. The long-term goal is to identify and characterize genetic (naturally occurring and induced) and environmental (toxicant and nutritional) causes of disruption of DNA methylation patterns during development and to determine their role in disease. The primary focus is on DNA methylation patterns during germ cell and early embryonic development during critical windows of epigenetic reprogramming.
Our research interests broadly span population genetics, statistical inference, and evolutionary genomics. We are interested in how evolutionary processes like changes in population size, recombination, mutation, selection and factors such as genome architecture shape patterns of genomic variation. Work in the lab involves employing computational and theoretical approaches, statistical method development, or using an empirical approach to perform evolutionary inference and ask fundamental questions in population genetics.
The goal of my research is to identify, clone, and characterize the evolution of genes underlying natural adaptations in order to determine the types of genes involved, how many and what types of genetic changes occurred, and the evolutionary history of these changes. Specific areas of research include: 1) Genetic analyses of adaptations and interspecific differences in Drosophila, 2) Molecular evolution and population genetics of new genes and 3) Evolutionary analysis of QTL and genomic data.
While both genes and environment are thought to influence human health, most investigations of complex disease only examine one of these risk factors in isolation. Accounting for both types of risk factors and their complex interactions allows for a more holistic view of complex disease causation. The Kelada lab is focused on the identification and characterization of these gene-environment interactions in airway diseases, particularly asthma, a disorder of major public health importance. / / Additionally, to gain insight into how the airway responds to relevant exposures (e.g., allergens or pathogens), we study gene expression in the lung (particularly airway epithelia). Our goal is identify the genetic determinants of gene expression by measuring gene expression across many individuals (genotypes). / This “systems genetics” approach allows us to identify master regulators of gene expression that may underlie disease susceptibility or represent novel therapeutic targets. /
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.
The Yun Li group develops statistical methods and computational tools for modern genetic, genomic, and epigenomic data. We do both method development and real data applications. The actual projects in the lab vary from year to year because I am motivated by real data problems, and genomics is arguably (few people argue with me though) THE most fascinating field with new types and huge amount of data generated at a pace more than what we can currently deal with. For current projects, please see: https://yunliweb.its.unc.edu/JobPostings.html
Dr. Lin is an infectious disease physician-scientist whose research lies at the interface of clinical and molecular studies on malaria. My current projects focus on 1) determinants of malaria transmission from human hosts to mosquitos and 2) the epidemiology and relapse patterns of Plasmodium ovale in East Africa. Work in my lab involves applying molecular tools (real-time PCR, amplicon deep sequencing, whole genome sequencing, and to a lesser extent antigen and antibody assays) to samples collected in clinical field studies to learn about malaria epidemiology, transmission, and pathogenesis.
Traditionally, basic science has sought to enter the translational pipeline through what can be referred to as “Bottom-Up” science, that is, studies that start with a hypothesis in the lab and aim to develop clinical relevance of the findings. In some cases, notably in conventional antibiotic development, this has worked well – but it assumes one-size fits all solutions that are only as good as our assumptions about the biology of many infectious diseases such as tuberculosis. By contrast, my research focuses on a “Top-Down” approach, leveraging the power of bacterial population genomics to identify bacterial processes important for Mtb success in people and to then employ cutting-edge experimental techniques to mechanistically dissect these processes with the goal of leveraging them using new translational tools.
In my work to date, I have applied this “Top-Down” strategy to define bacterial determinants of treatment outcomes and transmission success, as evident in first-author/corresponding author publications in prestigious journals such as Science, Nature Ecology Evolution, Cell Host Microbe, Science Advances, Genome Biology, PNAS, etc. My work combines expertise in evolutionary biology and bacterial genomics, cutting-edge bacterial genetics and high-throughput experimental phenotyping.
In my own lab, I will use these tools to (1) define the biological mechanisms that enable Mtb to survive antibiotic treatment; (2) identify bacterial determinants of TB transmission success; and (3) elucidate the evolutionary mechanisms underlying the emergence of new bacterial pathogens.
The Love Lab uses statistical models to infer biologically meaningful patterns in high-dimensional datasets, and develops open-source statistical software for the Bioconductor Project. At UNC-Chapel Hill, we often collaborate with groups in the Genetics Department and the Lineberger Comprehensive Cancer Center, studying how genetic variants relevant to diseases are associated with changes in molecular and cellular phenotypes.
The Magnuson Lab works in three areas – (i) Novel approaches to allelic series of genomic modifications in mammals, (ii)Mammalian polycomb-group complexes and development, (iii) Mammalian Swi/Snf chromatin remodeling complexes
We are a biological oceanography lab that performs inquiry-based science by combining physiological and molecular approaches in laboratory isolates and natural communities to investigate how marine microorganisms are affected by their environment and in turn, influence ocean biogeochemistry and ecosystem dynamics. Particular interests include studying trace metals, such as iron, that are essential for the nutrition of phytoplankton and predicting the effects of future climate changes on phytoplankton distribution and abundance. We implement the use of environmental genomic approaches (e.g. RNA-seq) to ascertain the ways in which marine microbes have adapted and acclimate to varying environmental conditions.
We are interested in the mechanisms by which histone protein synthesis is coupled to DNA replication, both in mammalian cell cycle and during early embryogenesis in Drosophila, Xenopus and sea urchins.
The research in our laboratory focuses on epigenetics and RNA processing. In particular, we are interested in the roles of small ribonucleoproteins (RNPs) and histone post-translational modifications in the regulation of eukaryotic gene expression. There are two main projects in the lab. (1) We have created a comprehensive genetic platform for histone gene replacement that — for the first time in any multicellular eukaryote — allows us to directly determine the extent to which histone post-translational modifications contribute to cell growth and development. (2) We study an RNP assembly factor (called Survival Motor Neuron, SMN) and its role in neuromuscular development and a genetic disease called Spinal Muscular Atrophy (SMA). Current work is aimed at a molecular understanding of SMN’s function in spliceosomal snRNP assembly and its dysfunction in SMA pathophysiology.
My research program studies how species form. We use a combination of approaches that range from field biology, behavior, and computational biology.
Research in the lab focuses on how a single genome gives rise to a variety of cell types and body parts during development. We use Drosophila as an experimental system to investigate (1) how transcription factors access DNA to regulate complex patterns of gene expression, and (2) how post-translational modification of histones contributes to maintenance of gene expression programs over time. We combine genomic approaches (e.g. CUT&RUN/ChIP, FAIRE/ATAC followed by high-throughput sequencing) with Drosophila genetics and transgenesis to address both of these questions.
Our laboratory is focused on translating novel molecular biomarkers into clinical oncology practice, with the overarching goal of improving the care and survival of patients with cancer. Our group is highly collaborative and applies genomic, genetic, bioinformatic, informatic, statistical, and molecular approaches. Current projects in the laboratory include:
- Correlative genomic testing to support clinical trials
- Expanded clinical applications of RNA sequencing
- Development and application of cell-free circulating tumor nucleic acid assays
The overall focus of our lab is to develop new and exciting approaches for enhancing the efficacy of cancer immunotherapies. We utilize cutting-edge techniques to identify transcriptional and epigenetic regulators controlling T cell differentiation and function in the tumor microenvironment, and we seek to leverage this insight to reprogram or tailor the activity of T cells in cancer. Our group is also interested in understanding how to harness or manipulate T cell function to improve vaccines and immunotherapies for acute and chronic infections.
We identify genetic variants that influence common human traits with complex inheritance patterns, and we examine the molecular and biological mechanisms of the identified variants and the genes they affect. Currently we are investigating susceptibility to type 2 diabetes and obesity, and variation in cholesterol levels, body size, body shape, and metabolic traits. We detect allelic differences in chromatin structure and gene expression and examine gene function in human cell lines and tissues. In addition to examining the primary effects of genes, the lab is exploring the interaction of genes with environmental risk factors in disease pathogenesis. Approaches include genome-wide association studies, molecular biology, cell biology, genetic epidemiology, sequencing, and bioinformatic analysis of genome-wide data sets.
The Morris lab leverages flexible mouse models of hard to treat cancers of the pancreas and liver to identify how cancer drivers perturb evolutionarily selected developmental programs and how such programs may be re-normalized. We focus on (1) the relationship between tumor suppressor pathways and the epigenetic determinants of cell plasticity, (2) evolutionary routes unleashed by specific tumor suppressor loss, and (3) how diversification at both the epigenetic and genomic level contribute to cancer development and therapeutic response.
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.
Non-Mendelian genetics including, meiotic drive, parent-of-orifin effects and allelic exclusion.
Dr. Parr’s research focuses on the infectious diseases of poverty, with translational projects in the Democratic Republic of the Congo (DRC) and other sites. His research concentrates on the molecular epidemiology of malaria and the evolution of “diagnostic-resistant” strains of Plasmodium falciparum, in particular. As a founding member of a World Health Organization laboratory network, he collaborates with malaria control programs and ministries of health to support surveillance of these parasites across Africa. His recent work in Ethiopia uncovered genetic signatures of strong positive selection favoring parasites with pfhrp2 gene deletion and influenced malaria diagnostic and surveillance policy in the Horn of Africa.
Dr. Parr has recently expanded his research program to include studies of other diseases that disproportionately impact marginalized populations worldwide, including viral hepatitis and syphilis, and serves as the director of the genomics core for a large NIH-funded syphilis vaccine development project that spans sites in Malawi, Columbia, China, North Carolina, and the Czech Republic.
Rotating students can expect to undertake translational projects that apply cutting-edge methodologies to real-world problems. Examples include application of novel enrichment methods that enable pathogen genomic sequencing from challenging field samples, development of CRISPR-based diagnostic assays, and evaluation of how infectious disease interventions affect pathogen population structure. Trainees will interact with diverse investigators and benefit from a highly collegial training environment in the Infectious Disease Epidemiology and Ecology Lab.
Dr. Parr continues to attend on the infectious disease inpatient services at UNC Medical Center and, in response to the pandemic, co-directed the UNC division of infectious diseases’ inpatient COVID-19 services. He also serves as Associate Editor for global health for Healthcare: The Journal of Delivery Science and Innovation. Dr. Parr and his work have been featured in the New York Times, Washington Post, CNN, and other media outlets.
The focus of my lab is to characterize the biological diversity of human tumors using genomics, genetics, and cell biology, and then to use this information to develop improved treatments that are specific for each tumor subtype and for each patient. A significant contribution of ours towards the goal of personalized medicine has been in the genomic characterization of human breast tumors, which identified the Intrinsic Subtypes of Breast Cancer. We study many human solid tumor disease types using multiple experimental approaches including RNA-sequencing (RNA-seq), DNA exome sequencing, Whole Genome Sequencing, cell/tissue culturing, and Proteomics, with a particular focus on the Basal-like/Triple Negative Breast Cancer subtype. In addition, we are mimicking these human tumor alterations in Genetically Engineered Mouse Models, and using primary tumor Patient-Derived Xenografts, to investigate the efficacy of new drugs and new drug combinations. All of these genomic and genetic studies generate large volumes of data; thus, a significant portion of my lab is devoted to using genomic data and a systems biology approach to create computational predictors of complex cancer phenotypes.
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.
We are interested in the links between epigenetics and gene regulation. Our primary focus is on understanding how changes to the composition of chromatin remodeling complexes are regulated, how their disruption affects their function, and contributes to disease. We focus on the SWI/SNF complex, which is mutated in 20% of all human tumors. This complex contains many variable subunits that can be assembled in combination to yield thousands of biochemically distinct complexes. We use a variety of computational and wet-lab techniques in cell culture and animal models to address these questions.
Keywords: genetic epidemiology, human genetics, genome-wide association studies, precision medicine, multi-omics, cardiovascular disease, inflammation, hematological traits
In my research program, I use human genomics and multi-omics to understand inherited and environmental risk factors for cardiometabolic diseases and related quantitative traits. I work to link genetic variants to function through integration with multi-omics data, including transcriptomic, methylation, proteomic, and metabolomic measures. This work has important implications for cardiometabolic risk prediction across diverse populations and improved understanding of disease biology. A focus on understudied African American and Hispanic/Latino populations is a central theme of my research; human genetics research is dramatically unrepresentative of global populations, with ~95% of genome-wide association study participants of European or East Asian ancestry. As complex trait genetics moves into the clinic, increasing diversity is essential to ensure that all populations benefit from the promise of precision medicine.
I play a leadership role in collaborative efforts in human genetics, for example serving as a Genetics Working Group co-chair for the Jackson Heart Study (JHS), one of the largest population based studies of African Americans, and an Inflammation/Hematology working group co-chair for the Population Architecture Using Genomics and Epidemiology (PAGE) consortium. I am also a co-convener of the Multi-Omics working group for the NHLBI Trans-Omics for Precision Medicine (TOPMed) program.
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.
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.
I work on predicting the determinants of adaptive immune responses. Most of my work has focused on T-cell epitope prediction for mutant antigens derived from cancer. I have collaborated closely with clinical groups to translate this work in personalized cancer vaccine trials. More recently I have also been working on joint T-cell and B-cell prediction for viral pathogens. The technologies and techniques applied across all of my projects are at the intersection of computational immunology, genomics, and machine learning.
The Schisler Lab is geared towards understanding and designing therapies for diseases involving proteinopathies- pathologies stemming from protein misfolding, aggregation, and disruption of protein quality control pathways. We focus on cardiovascular diseases including the now more appreciated overlap with neurological diseases such as CHIPopathy (or SCAR16, discovered here in our lab) and polyQ diseases. We use molecular, cellular, and animal-based models often in combination with clinical datasets to help drive our understanding of disease in translation to new therapies.
I am a surgeon-scientist specialized in head and neck cancers. My goal is to address translationalquestions with genomic data and bioinformatic methods, as well as benchtop experimentation. My clinical practice as a head and neck cancer surgeon also influences my research by helping me seek solutions to problems that will directly inform gaps in the current treatment protocols.
I have developed a strong interest in HPV genomics as well as HPV/host genome integrations, as these factors are intrinsically related to transcriptional diversity and patient outcomes in HPV-associated head and neck cancers. Our work has helped to demonstrate that a novel mechanism of HPV-mediated oncogenesis requiring NF-kB activation is present in nearly 50% of oropharyngeal tumors. In this vein, we are aggressively investigating the cellular interplay between the NF-kB pathway and persistent HPV infection, tumor radiation response, NRF2 signaling, and more.
Another outgrowth of this work has been investigating APOBEC3B and its non-canonical roles in regulating transcription. Our preliminary work has demonstrated that APOBEC3B has surprisingly strong transcriptional effects in HPV+ HNSCC cells and may promote oncogenesis and tumor maintenance by suppressing the innate immune response and influencing the HPV viral lifecycle.
Our group also have a strong interest in translational genomic studies. Our group is working to develop methods that will make gene expression-based biomarkers more successful in the clinic, as well as studying many aspects of genomic alterations that contribute to the development of squamous cell carcinomas.
The Schrider Lab develops and applies computational tools to use population genetic datasets to make inferences about evolutionary history. Our research areas include but are not limited to: characterizing the effects natural selection on genetic variation within species, identifying genes responsible for recent adaptation, detecting genomic copy number variants and other weird types of mutations, and adapting machine learning tools for application to questions in population genetics and evolution. Study organisms include humans, the fruit fly Drosophila melanogaster and its relatives, and the malaria vector mosquito Anopheles gambiae.
Genome instability is a major cause of cancer. We use the model organism Drosophila melanogaster to study maintenance of genome stability, including DNA double-strand break repair, meiotic and mitotic recombination, and characterization of fragile sites in the genome. Our primary approaches are genetic (forward and reverse, transmission and molecular), but we are also using biochemistry to study protein complexes of interest, genomics to identify fragile sites and understand the regulation of meiotic recombination, fluorescence and electron microscopy for analysis of mutant phenotypes, and cell culture for experiments using RNA interference.
We seek to understand how information is encoded and dynamically utilized in immune cells from healthy and disease prone intestines (The Inflammatory Bowel Diseases: Crohn’s disease and Ulcerative Colitis). Our lab is multi-disciplinary and combines high-throughput genomics with innate immunity and microbiology. We focus specifically on genes that regulate response to the bacteria that normally reside in our intestines. Many of these genes make products that regulate the immune system in the intestine. These products defend the intestine against the attack of foreign materials; such as bacteria that live in the intestine. We use genome-sequencing technology to precisely identify regions throughout the genome that are potential ‘on’ or ‘off’ switches for these genes. There is a fine balance between the genes that produce inflammatory substances that are necessary to kill bacteria and genes that produce anti-inflammatory substances that are important to prevent damage to the intestine. If this balance between inflammatory and anti-inflammatory substance production in the intestine is disrupted, IBD may result. Our lab focuses on understanding how these important controllers of inflammation are turned on and off in IBD. We also study how inflammatory and anti-inflammatory signals impact disease severity, progression and response to therapy in individuals with IBD. This information has the potential to increase our understanding of causes of IBD (personalized medicine) and to contribute to the development of new treatments.
Our laboratory studies the coordination of histone-modifying enzymes in regulating chromatin structure, enhancer activation, and transcription. We utilize mouse genetics and cell culture model systems to study the mechanisms of enhancer activation in neural crest cell epigenetics, craniofacial development, and altered enhancer regulation in cancer. This is accomplished through a variety of techniques including mouse mutagenesis, fluorescent reporters to isolate primary cells of interest, low cell number genomics, and proteomic approaches.
We are interested in elucidating context-specific functions of products from single long noncoding RNA (lncRNA) loci. Since lncRNAs have been implicated in many cellular processes, it is critical to delineate specific roles for each lncRNA. Moreover, as they are increasingly associated with diseases including developmental disorders, degenerative diseases, and cancers, defining their functions will be an important precursor to their use as diagnostics and therapeutics. We specialize in adopting -omics approaches including genomics, transcriptomics and proteomics, combined with single molecule methods to study the intermolecular interactions – RNA-protein, RNA-RNA and RNA-chromatin that lncRNAs use to execute their functions in normal stem cells and cancer.
We are a lab exploring how variations in the genome change the structure and development of the brain, and in doing so, create risk for neuropsychiatric illness. We study genetic effects on multiple aspects of the human brain, from macroscale phenotypes like gross human brain structure measured with MRI to molecular phenotypes like gene expression and chromatin accessibility measured with genome-sequencing technologies. We also use neural progenitor cells as a modifiable and high fidelity model system to understand how disease-associated variants affect brain development.
I study complex traits using linkage, association, and genetic epidemiological approaches. Disorders include schizophrenia (etiology and pharmacogenetics), smoking behavior, and chronic fatigue.
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.
Dr. Troester’s research focuses on stromal-epithelial interactions, genomics of normal breast tissue, breast cancer microenvironment, and molecular pathology of breast cancer progression. She is a Co-Investigator on the Carolina Breast Cancer Study (CBCS), a resource including breast tumors from thousands of African American women, and she is PI of the Normal Breast Study (NBS), a unique biospecimen resource of normal tissue from women undergoing breast surgery at UNC Hospitals. Dr. Troester has extensive experience in integrating multiple high dimensional data types. She is chair of the Normal Breast Committee for the Cancer Genome Atlas Project where she is leading coordination of histology, copy number, mutation, methylation, mRNA and microRNA expression data. She has more than a decade of experience working with genomic data and molecular biology of breast cancer progression and has published many papers in the area of breast cancer subtypes, breast microenvironment, and stromal-epithelial interactions. She has trained four postdocs, 12 predoctoral students and several undergraduates.
We aim to dissect the epigenetic and transcriptional mechanisms that shape T cell lineage specification during development in the thymus and in the periphery upon antigen (microbial, viral) encounter. Aberrant expression of transcription and epigenetic factors can result in inflammation, autoimmunity or cancer. We are using gene deficient mouse models, multiparameter Flow Cytometry, molecular biology assays and next generation sequencing technologies to elucidate the regulatory information in cells of interest (transcriptome, epigenome, transcription factor occupancy).
We are a quantitative genetics lab interested the relationship between genes and complex disease. Most of our work focuses on developing statistical and computational techniques for the design and analysis of genetic experiments in animal models. This includes, for example: Bayesian hierarchical modeling of gene by drug effects in crosses of inbred mouse strains; statistical methods for identifying quantitative trait loci (QTL) in a variety of experimental mouse populations (including the Collaborative Cross); computational methods for optimal design of studies on parent of origin effects; modeling of diet by gene by parentage interactions that affecting psychiatric disease; detection and estimation of genetic effects on phenotypic variability. For more information, visit the lab website.
The Vincent laboratory focuses on immunogenomics and systems approaches to understanding tumor immunobiology, with the goal of developing clinically relevant insights and new cancer immunotherapies. Our mission is to make discoveries that help cancer patients live longer and better lives, focusing on research areas where we feel our work will lead to cures. Our core values are scientific integrity, continual growth, communication, resource stewardship, and mutual respect.
Our lab uses computational and molecular tools to study the evolution of genome organization, primarily in the flowering plants. Areas of
investigation include the origin and consequences of differences in gene order within populations and between species, the evolutionary and functional diversification of gene families (phytome.org), and the application of genomics to evolutionary model organisms (mimulusevolution.org). We also are involved in a number of cyberinfrastructure initiatives through the National Evolutionary Synthesis Center (nescent.org), including work on digital scientific libraries (datadryad.org), open bioinformatic software development (e.g. gmod.org) and the application of semantic web technologies to biological data integration (phenoscape.org).
My research interests are focused on understanding the effects of genetic and environmental factors and their interaction on complex human diseases using a combination of statistical, molecular and bioinformatics approaches. My specific interests include understanding the influence of genetic variants on serum uric acid levels (a biomarker for renal-cardiovascular disease), effect of gene by diet interactions on serum uric acid levels and associated renal-cardiovascular disease risk factors and identification of functional variants affecting these disorders that will lead to novel treatment options.
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.
Our research focuses on long-read (single-molecule) sequencing and informatics. We develop novel methods to enable more efficient *omic analysis and apply carefully architected high-performance computing approaches to improve the utility of genomics in studies of human diseases, including infectious disease, cancer, and GI. Ongoing work includes genomic epidemiology of SARS-CoV-2, MPXV, and antibiotic resistance; classification of pediatric leukemias and solid tumors in low-resource settings using nanopore transcriptome sequencing; and metagenomics/metataxonomics of mucosa-associated microbiota in inflammatory bowel diseases.
We are actively engaged in multiple research arenas centered around understanding the associations between environmental exposures (primarily air pollution) and health outcomes. We use large clinical cohorts and electronic health records to understand associations between air pollution and health outcomes such as cardiovascular disease, metabolic disease, and aging. We use metabolomics and epigenetic data (primarily DNA methylation) to investigate molecular mechanisms, and highlight the integration of ‘omics data in a systems biology framework to better understand dysregulated pathways. Finally, we have projects centered around methods development and causal analyses to improve our understanding of the biology central to environmental health effects.
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.
Our group develops novel statistical bioinformatics tools and applies them in biomedical research to help understanding the precision medicine for cancer (e.g., breast cancer and lung cancer) subtypes, the disease associated integrative pathways across multiple genomic regulatory levels, and the genetics based drug repurposing mechanisms. Our recent focus includes pathway analysis, microbiome data analysis, data integration and electronica medical records (EMR). Our application fields include cancer, stem cell, autoimmune disease and oral biology. In the past, we have developed gene set testing methods with high citations, in the empirical Bayesian framework, to take care of small complex design and genewise correlation structure. These have been widely used in the microarray and RNAseq based gene expression analysis. Contamination detection for data analysis for Target DNA sequencing is work in progress. Recently, we also work on single cell sequencing data for pathway analysis with the local collaborators.
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.
My research has been concentrated on the areas of statistical genetics and genomics to investigate the role of genetic variations on complex quantitative traits and diseases. I work primarily in the development, as well as the examination of statistical properties, of theoretical methodologies appropriate for the interpretation of genetic data.
Our research is focused on two general areas: 1. Autism and 2. Pain. Our autism research is focused on topoisomerases and other transcriptional regulators that were recently linked to autism. We use genome-wide approaches to better understand how these transcriptional regulators affect gene expression in developing and adult neurons (such as RNA-seq, ChIP-seq, Crispr/Cas9 for knocking out genes). We also assess how synaptic function is affected, using calcium imaging and electrophysiology. In addition, we are performing a large RNA-seq screen to identify chemicals and drugs that increase risk for autism. / / Our pain research is focused on lipid kinases that regulate pain signaling and sensitization. This includes work with cultured dorsal root ganglia (DRG) neurons, molecular biology and behavioral models of chronic pain. We also are working on drug discovery projects, with an eye towards developing new therapeutics for chronic pain.