BBSP Faculty
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 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.
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.
How do networks of cells synchronize behaviors across differing spatial and temporal scales? This fundamental aspect of cellular dynamics is broadly relevant to understanding many biological systems in which the coherence of electrical or chemical signals is required for multicellular patterning or organ function. Our group’s primary research interests are related to understanding the cellular and microenvironmental conditions that are required to support the biorhythmic behavior of the system of cells that natively control heart rate, cardiac pacemaker cells. We utilize a variety of techniques including computational modeling, next generation sequencing, in vivo genetic manipulation, super-resolution imaging, and direct physiological recording to investigate the developmental processes that assemble the hearts pacemaking complex. The ultimate goals of these studies is to determine how the pacemaker cell lineage is patterned in the embryo, build strategies towards fabricating this cell type for therapeutic purposes, and identify vulnerabilities that may lead to pacemaker cell pathologies in humans.
My research lab focuses on the molecular pathogenesis of endometrial cancer, the most common gynecologic cancer in the Western world. Current projects include developing molecular diagnostics for predicting endometrial cancer histotype, stage, and recurrence; developing clinical and lab-based algorithms for the identification of patients with hereditary endometrial cancer (Lynch Syndrome); discovering novel molecular mediators of endometrial cancer invasion and metastasis; identifying signaling pathways important in the pathogenesis of endometrial cancer; and identifying molecular determinants of health disparities in endometrial cancer.
Cross-talk between insulin like growth factor -1 and cell adhesion receptors in the regulation of cardiovascular diseases and complications associated with diabetes.
Our lab is interested in molecular mechanisms of oncogenesis, specifically as regulated by Ras and Rho family small GTPases. We are particularly interested in understanding how membrane targeting sequences of these proteins mediate both their subcellular localization and their interactions with regulators and effectors. Both Ras and Rho proteins are targeted to membranes by characteristic combinations of basic residues and lipids that may include the fatty acid palmitate as well as farnesyl and geranylgeranyl isoprenoids. The latter are targets for anticancer drugs; we are also investigating their unexpectedly complex mechanism of action. Finally, we are also studying how these small GTPases mediate cellular responses to ionizing radiation – how do cells choose whether to arrest, die or proliferate?
The Cyr laboratory studies cellular mechanisms for cystic fibrosis and prion disease. We seek to determine how protein misfolding leads to the lung pathology associated with Cystic Fibrosis and the neurodegeneration associated with prion disease.
A major focus of the Diekman lab is to develop new strategies to limit age-related osteoarthritis (OA). The lab uses genetically-engineered mouse models to investigate the development of cellular senescence in joint tissues with physiologic aging. One goal of this work is to determine whether “senolytic” compounds that induce selective apoptosis in senescent cells will mitigate OA development. Our group has also developed genome-editing protocols for primary human chondrocytes to produce single-cell derived colonies with homozygous knockout of target genes. We are using engineered tissues from these cells to dissect the mechanism of genes implicated in OA development by genome-wide association studies, as well as coupling these technologies to high throughput screening approaches for OA drug discovery.
We study host defense mechanisms in the lungs, particularly the inflammatory and innate immune processes important in the pathogenesis and course of bacterial pneumonia, acute lung injury/acute respiratory distress syndrome, and cigarette smoke-associated lung disease. Basic and translational studies address mechanisms of host defense, including recruitment and function of leukocytes, vascular permeability leading to edema, bacterial clearance and resolution. Cell signaling pathways initiated by binding of leukocyte-endothelial cell adhesion molecules and molecular mechanisms underlying the functions of neutrophils are two particular areas.
The research in my lab is divided into two main areas – 1) Atomic force microscopy and fluorescence studies of protein-protein and protein-nucleic acid interactions, and 2) Mechanistic studies of transcription elongation. My research spans the biochemical, biophysical, and analytical regimes.
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.
The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has significantly elevated in the last years and continues to increase; however, despite the continuous rise of HPV-related OPSCC, molecular mechanisms of how HPV promotes OPSCC are not well defined. Our ongoing research projects focus on understanding the role of HPV in the development, maintenance, and progression of head and neck squamous cell carcinoma (HNSCC). These discoveries are leveraged to identify and test novel therapeutic strategies that exploit susceptibilities of HPV-associated HNSCC.
The Jarstfer lab uses an interdisciplinary approach to solve biological problems that are germane to human health. Currently we are investigating the structure of the enzyme telomerase, we are developing small-molecules that target the telomere for drug discovery and chemical biology purposes, and we are investigating the signals that communicate the telomere state to the cell in order to control cellular immortality. We are also engaged in a drug/chemical tool discovery project to identify small molecules that control complex social behavior in mammals. Techniques include standard molecular biology and biochemistry of DNA, RNA, and proteins, occasional organic synthesis, and high throughput screening.
Antiretroviral therapy (ART) is effective in suppressing HIV-1 replication in the periphery, however, it fails to eradicate HIV-1 reservoirs in patients. The main barrier for HIV cure is the latent HIV-1, hiding inside the immune cells where no or very low level of viral particles are made. This prevents our immune system to recognize the latent reservoirs to clear the infection. The main goal of my laboratory is to discover the molecular mechanisms how HIV-1 achieves its latent state and to translate our understanding of HIV latency into therapeutic intervention.
Several research programs are undertaking in my lab with a focus of epigenetic regulation of HIV latency, including molecular mechanisms of HIV replication and latency establishment, host-virus interaction, innate immune response to viral infection, and the role of microbiome in the gut health. Extensive in vitro HIV latency models, ex vivo patient latency models, and in vivo patient and rhesus macaque models of AIDS are carried out in my lab. Multiple tools are applied in our studies, including RNA-seq, proteomics, metabolomics, highly sensitive digital droplet PCR and tissue RNA/DNAscope, digital ELISA, and modern and traditional molecular biological and biochemical techniques. We are also very interested in how non-CD4 expression cells in the Central Nervous System (CNS) get infected by HIV-1, how the unique interaction among HIV-1, immune cells, vascular cells, and neuron cells contributes to the initial seeding of latent reservoirs in the CNS, and whether we can target the unique viral infection and latency signaling pathways to attack HIV reservoirs in CNS for a cure/remission of HIV-1 and HIV-associated neurocognitive disorders (HAND). We have developed multiple tools to attack HIV latency, including latency reversal agents for “Shock and Kill” strategy, such as histone deacetylase inhibitors and ingenol family compounds of protein kinase C agonists, and latency enforcing agents for deep silencing of latent HIV-1. Several clinical and pre-clinical studies are being tested to evaluate their potential to eradicate latent HIV reservoirs in vivo. We are actively recruiting postdocs, visiting scholars, and technicians. Rotation graduate students and undergraduate students are welcome to join my lab, located in the UNC HIV Cure Center, for these exciting HIV cure research projects.
Our lab is focused on the development of HIV-1 vectors for gene therapy of genetic disease. In addition, we are using the vector system to study HIV-1 biology. We are also interested in utilizing the HIV-1 vector system for functional genomics.
We focus on a variety of design goals including the creation of novel protein-protein interactions, protein structures, vaccine antigens and light activatable protein switches. Central to all of our projects is the Rosetta program for protein modeling. In collaboration with developers from a variety of universities, we are continually adding new features to Rosetta as well as testing it on new problems.
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.
Our research is focused on the genetics and molecular pathology of complex multi-factorial conditions in humans –hypertension especially pregnancy related hypertension such as preeclampsia. We have identified that endothelin-1 plays a causative role in developing preeclampsia. Now we are focusing on elucidating the mechanisms underlying this phenomenon, particularly on how the endothelin system affects the embryonic implantation on the early stage of pregnancy.
My research has focused on developing new radio-chemistry, imaging probes, and therapeutic approaches including nanomedicine for various diseases. Most importantly, we have the culture of forming an active collaboration with people in different field. With a cGMP lab located within our facility, we are also experienced on developing lead agents and translate it to clinic.
Dr. Lin is an infectious disease physician-scientist whose research lies at the interface of clinical and molecular studies on malaria. My current projects focus on 1) determinants of malaria transmission from human hosts to mosquitos and 2) the epidemiology and relapse patterns of Plasmodium ovale in East Africa. Work in my lab involves applying molecular tools (real-time PCR, amplicon deep sequencing, whole genome sequencing, and to a lesser extent antigen and antibody assays) to samples collected in clinical field studies to learn about malaria epidemiology, transmission, and pathogenesis.
The Loeser lab uses a combination of in vitro studies in articular chondrocytes and in vivo studies in mice to examine molecular mechanisms of joint tissue destruction in aging and osteoarthritis. A major focus of this work is examining how reactive oxygen species regulate cell signaling through oxidation of Cys residues in specific kinases and phosphatases. Pathways of interest include integrin mediated signaling that stimulates matrix metalloproteinase (MMP) expression and IGF-I signaling that stimulates matrix production. Oxidative stress disrupts the balance in the activity of these pathways to favor matrix destruction over repair contributing to the development of osteoarthritis.
The overall goal of our laboratory is to obtain new insights into the host-virus interaction, particularly in HIV infection, and translate discoveries in molecular biology and virology to the clinic to aid in the treatment of HIV infection. A subpopulation of HIV-infected lymphocytes is able to avoid viral or immune cytolysis and return to the resting state. Current work focuses on the molecular mechanisms that control the latent reservoir of HIV infection within resting T cells. We have found that cellular transcription factors widely distributed in lymphocytes can remodel chromatin and maintain quiescence of the HIV genome in resting CD4+ lymphocytes. These studies give insight into the basic molecular mechanisms of eukaryotic gene expression, as well as new therapeutic approaches for HIV infection.
We 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.
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 major area of our research is Biomolecular Informatics, which implies understanding relationships between molecular structures (organic or macromolecular) and their properties (activity or function). We are interested in building validated and predictive quantitative models that relate molecular structure and its biological function using statistical and machine learning approaches. We exploit these models to make verifiable predictions about putative function of untested molecules.
Our lab uses human genetics to identify new mechanisms driving coronary artery disease (CAD). Starting with findings from genome-wide association studies (GWAS) of CAD, we identify the causal gene at a given locus, study the effect of this gene on cellular and vessel wall biology, and finally determine the molecular pathways by which this gene influences CAD risk. Within this framework, we use complex genetic mouse models and human vascular samples, single-cell transcriptomics/epigenomics and high-throughput CRISPR perturbations, as well as traditional molecular biology techniques.
We investigate mechanisms in blood coagulation and diseases that intersect with abnormal blood biomarkers and function, including cardiovascular disease (heart attack, stroke, deep vein thrombosis, pulmonary embolism), bleeding (hemophilia), inflammation, obesity, and cancer. We also investigate established drugs and new drugs in preclinical development to understand their role in reducing and preventing disease. Our studies use interdisciplinary techniques, including in vitro, ex vivo, and in vivo mouse models and samples from humans in translational studies that span clinic to bench. Our lab emphasizes a culture of diversity, responsibility, independence and collaboration, and shared excitement for scientific discovery. We are located in the UNC Blood Research Center in the newly-renovated Mary Ellen Jones building.
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.