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

The Arthur lab is interested in mechanisms by which inflammation alters the functional capabilities of the microbiota, with the long-term goal of targeting resident microbes as a preventative and therapeutic strategy to lessen inflammation and reduce the risk of colorectal cancer. We utilize a unique and powerful in vivo system – germ-free and gnotobiotic mice – to causally link specific microbes, microbial genes, and microbial metabolites with health and disease in the gut.  We also employ basic immunology and molecular microbiology techniques as well as next generation sequencing and bioinformatics to evaluate these essential host-microbe interactions.

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.

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

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

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

Our lab is interested in the molecular mechanisms of adaptive stress responses. These responses to environmental or metabolic stress are essential for survival but frequently dysregulated in disease. We use an integrated approach combining biophysical, structural, and biochemical methods to investigate the roles of intrinsically disordered proteins and dynamic enzymes that orchestrate these critical stress responses, with the ultimate goal of developing new approaches for modulating the functions of dynamic molecules.

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.

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.

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

Our research group uses several biochemical and structural techniques (e.g. enzyme assays, X-ray crystallography, and cryo-EM) to understand how molecular machines drive the cell cycle. Dysregulation of these enzymes results in numerous cancer types.

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.

The overall goal of our lab is to perform research that contributes to a better understanding of pancreatic cancer biology and leads to improved treatments for this disease. One major focus of our studies is the metabolic activity, autophagy, which is a self-degradation process whereby cells can orderly clear defective organelles and recycle macromolecules as a nutrient source. Current projects are focused on further advancing autophagy inhibition as an anti-RAS therapeutic approach, as well as delineating other metabolic consequences of RAF-MEK-ERK MAPK inhibition.

Developing and applying novel mass spectrometry (MS)-based proteomics methodologies for high throughput identification, quantification, and characterization of the pathologically relevant changes in protein expression, post-translational modifications (PTMs), and protein-protein interactions. Focuses in the lab include: 1) technology development for comprehensive and quantitative proteomic analysis, 2) investigation of systems regulation in toll-like receptor-mediated pathogenesis and 3) proteomic-based mechanistic investigation of stress-induced cellular responses/effects in cancer pathogenesis.

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

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.

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.

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 work in our laboratory is focused on understanding the molecular pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV), an oncogenic human virus. KSHV is associated with several types of cancer in the human population. We study the effect of KSHV viral proteins on cell proliferation, transformation, apoptosis, angiogenesis and cell signal transduction pathways. We also study viral transcription factors, viral replication, and the interactions of KSHV with the human innate immune system. Additionally, we are developing drug therapies that curb viral replication and target tumor cells.

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

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

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

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

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).

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.

The Drewry lab is focused on designing, synthesizing, evaluating, and sharing small molecule chemical probes for protein kinases. These tools are used to build a deeper understanding of disease pathways and facilitate identification of important targets for drug discovery. Through wide ranging partnerships with academic and industrial groups, the Drewry lab is building a Kinase Chemogenomic Set (KCGS) that is available to the community for screening.

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 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.

Our research interests focus on the immunologic and genetic mechanisms of lymphomagenesis, particularly in the setting of HIV infection. While hematologic malignancies and lymphoproliferative disorders in sub-Saharan Africa (SSA) arise under intrinsic and extrinsic pressures very different from those in the United States, comprehensive analyses of these diseases have not been performed. We use advanced sequencing, immunophenotypic and cellular analyses to address gaps in our understanding of lymphomagenesis and tumor microenvironment in the context of HIV-associated immune dysregulation, with the goal of translation to clinical care and future clinical trials.

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

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

Our primary research is in the area of computational systems biology, with particular interest in the study of biological signaling networks; trying to understand their structure, evolution and dynamics. In collaboration with wet lab experimentalists, we develop and apply computational models, including probabilistic graphical and multivariate methods along with more traditional engineering approaches such as system identification and control theory, to current challenges in molecular biology and medicine. Examples of recent research projects include: prediction of protein interaction networks, multivariate modeling of signal transduction networks, and development of methods for integrating large-scale genomic data sets.

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

During cell shape change and motility, a dynamic cytoskeleton produces the force to initiate plasma membrane protrusion, while vesicle trafficking supplies phospholipids and membrane proteins to the expanding plasma membrane. Extracellular cues activate intracellular signaling pathways to elicit specific cell shape changes and motility responses through coordinated cytoskeletal dynamics and vesicle trafficking. In my lab we are investigating the role of two ubiquitin ligases, TRIM9 and TRIM67, in the cell shape changes that occur during neuronal development. We utilize a variety techniques including high resolution live cell microscopy, gene disruption, mouse models, and biochemistry to understand the complex coordination of cytoskeletal dynamics and membrane trafficking driving neuronal shape change and growth cone motility in primary neurons.

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

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.

Dr. Hursting’s lab focuses on the molecular and metabolic mechanisms underlying nutrition and  cancer associations, particularly the impact of obesity and energy balance modulation (eg, calorie restriction, exercise) on cancer development or responses to chemotherapy. Primarily using genetically engineered mouse models of pancreatic, colon and breast cancer, Dr. Hursting has identified the IGF-1/Akt/mTOR and NF-kB signaling pathways as key targets for breaking the obesity- cancer link.  He has also established in several preclinical models of pancreatic and breast cancer that obesity impacts the response to various forms of chemotherapy.  In addition, the Hursting lab is involved in several translational research collaborations linking mouse model studies with clinical trials, and his group has expertise in measuring metabolic hormones, growth factors, inflammatory cytokines and chemokines in serum and tissue from rodents and humans.

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.

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.

Dr. Krupenko’s research is focused on the role of folate metabolism in cellular homeostasis and cancer disease. He is especially interested in the function of a major folate enzyme and a putative tumor suppressor ALDH1L1 as metabolic regulator and a guardian of non-malignant phenotype. At present he studies function of this enzyme and related proteins using mouse knockout models. Recently his research team has also demonstrated that dietary folate regulates cancer metastasis. He now pursues studies of specific signaling pathways involved in metastatic response to dietary folate status.

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.

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

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

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

Research in the Lockett group focuses on the development of analytical model systems to: i) chemically modify the surface of thin films, and study chemical and biochemical reactions occurring on those surfaces; ii) study drug metabolism in an environment that closely mimics the human liver; iii) measure tumor invasion in an environment that closely mimics human tissue. /  / While these problems require techniques found in analytical chemistry, biochemistry, molecular biology, bioengineering, and surface science we are particularly interested in the technologies that allow us to quantitatively measure reactions and analytes.

The major focus of Mackman lab is the procoagulant protein tissue factor. This is the primary cellular initiator of blood coagulation. We study its role in hemostasis, thrombosis, inflammation, ischemia-reperfusion injury and tumor growth.  We have generated a number of mouse models expressing different levels of both mouse and human tissue factor. These mice have been used to provide new insights into the role of tissue factor in hemostasis and thrombosis. In 2007, we developed a new assay to measure levels of microparticle tissue factor in plasma. We found that elevated levels of microparticle tissue factor are associated with venous thromboembolism in cancer patients.

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

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

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

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

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:

1. Correlative genomic testing to support clinical trials
2. Expanded clinical applications of RNA sequencing
3. Development and application of cell-free circulating tumor nucleic acid assays

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

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.

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.

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.

The Palmer lab investigates combination cancer therapy: understanding the mechanisms of successful drug combinations to inform the development of combinations with new cancer therapies. Our approach is a synthesis of experiments, analysis of clinical data, and modeling. Students can pursue projects that are experimental, computational, or a mixture of both. Our goals are to improve the design of drug combinations, the interpretation of clinical trials, and patient stratification to increase rates of response and cure through more precise use of cancer medicines in combinations.

Pecot Lab: Therapeutic RNAi to Teach Cancer how to “Heal” and Block Metastatic Biology

Synopsis: The Pecot lab is looking for eager, self-motivated students to join us in tackling the biggest problem in oncology, metastases. An estimated 90% of cancer patients die because of metastases. However, the fundamental underpinnings of what enables metastases to occur are poorly understood. The Pecot lab takes a 3-pronged approach to tackling this problem: 1) By studying the tumor microenvironment (TME), several projects are studying how cancers can be taught to “heal” themselves, 2) By studying how cancers manipulate non-coding RNAs (micro-RNAs, circle RNAs, snoRNAs, etc) to promote their metastatic spread, and 3) We are investigating several ways to develop and implement therapeutic RNA interference (RNAi) to tackle cancer-relevant pathways that are traditionally regarded as “undruggable”. Students joining the lab will be immersed in the development of novel metastatic models, modeling and studying the TME both in vitro and in vivo, using bioinformatic approaches to uncover mechanistic “roots”, and implementation of therapeutic approaches

Cell adhesion, cytoskeletal regulation and Wnt signaling in development and cancer
The Peifer lab works at the interface between cell, developmental, and cancer biology, focusing on the epithelial tissues that form the basic architectural unit of our bodies and of those of other animals. We explore how the machinery mediating cell adhesion, cytoskeletal regulation and Wnt signaling regulates cell fate and tissue architecture in development and disease. We take a multidisciplinary approach, spanning genetics, cutting edge cell biology including super-resolution microscopy, biochemistry and computational approaches. We use the fruit fly Drosophila as an animal model and combine that with work in cultured normal and colorectal cancer cells. Possible thesis projects include exploring how connections between cell junctions and the cytoskeleton are remodeled to allow cells to change shape and move without tearing tissues apart or exploring how the tumor suppressor protein APC assembles a multi-protein machine that negatively regulates Wnt signaling and how this goes wrong in colorectal tumors. I am a hands on-mentor with an open-door policy and my office is in the lab. I value and advocate for diversity. Our lab has a strong record of training PhD students and postdocs who move on to success in diverse science-related careers. Our lab is funded by a long-standing NIH grant that extends to July 2021, and just received a good score for renewal. To learn more about or research, our recent publications, our team and our alumni check out the lab website at: https://proxy.qualtrics.com/proxy/?url=http%3A%2F%2Fpeiferlab.web.unc.edu%2F&token=1rPNJvHEEfhAAiwkSviuOG0Fg8%2ByN3Q3GMob1A2GJwM%3D

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

My graduate students and I use the formalism of equilibrium thermodynamics and the tools of molecular biology and biophysics to understand how nature designs proteins.

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

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.

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

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.

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.

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

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

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.

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.

The Serody laboratory focuses on tumor and transplant immunology studies using both animal models and translational work with clinical samples. We have performed pioneering work in both of these areas. Our laboratory was the first to describe a role for migratory proteins in the biology of acute GVHD. We were the first group to use eGFP transgenic mice generated in part by our group to track the migration of donor cells after transplant. This work showed a critical role for lymphoid tissue in the activation of donor T cells. Most recently we have been the first group to demonstrate the absence of ILC2 cells in the GI tract after all types of transplant and we have generated novel studies into the ILC2 niche in the bone marrow. For our tumor work we were one of the first groups to use genomic evaluations of the tumor microenvironment to characterize the immune response in cancer models. We were the first group to demonstrate how to enhance checkpoint inhibitor therapy in triple negative breast cancer models and have been one of the leading groups in performing genomic evaluations using TCGA data. Finally, we are one of the leading groups in the world characterizing the role of B cells in the anti-tumor immune response.

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.

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 studies signal transduction systems controlled by heterotrimeric G proteins as well as Ras-related GTPases using a variety of biophysical, biochemical and cellular techniques. Member of the Molecular & Cellular Biophysics Training Program.

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.

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

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.

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.

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.

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.

The overall objective of our research is to understand the connection between structure of protein-DNA complexes, protein dynamics and function.  We currently focus on the methyl-cytosine binding domain (MBD) family of DNA binding proteins.  The MBD proteins selectively recognize methylated CpG dinucleotides and regulate gene expression critical for both normal development and carcinogenesis.  We use a combination of NMR spectroscopy and biophysical analyses to study protein-DNA and protein-protein complexes involving the MBD proteins.  Building on these studies, we are developing inhibitors of complex formation as potential molecular therapeutics for b-hemoglobinopathies and cancer.

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

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

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

Our 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.

Our translational research lab is focused on the earliest changes that occur in the uterus (endometrium) during cancer development related to obesity and hereditary DNA repair defects. We use preclinical tools (rodents, organoids, and cell lines) to probe mechanisms of endometrial cancer pathogenesis, in parallel with human tissue studies. Our overall goal is to understand how environmental factors, including obesity, hormones, and other exposures, influence endometrial cancer development and disparities so that we can use pharmacologic agents to prevent or reverse cancer development.

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.

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

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