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Dr. Alexander works at the interface cancer genomics, clinical trials, and global pediatric oncology with three areas of research focus

1) Investigation of new cancer therapeutics through early phase clinical trials for high risk acute leukemia

2) Exploration of the biology of minimal residual disease in acute lymphoblastic leukemia, through RNA sequencing and epigenetic studies, at both a bulk and single cell level. The ultimate goal is to develop more rational therapeutic targets for patients with persistent MRD.

3) Development of a novel genomic sequencing approach for cancer diagnostics in low and middle income counties.


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 develops new chemistry, and chemical agents as biological probes and drug discovery candidates. Current interests include the discovery of unconventional opioid agents, anti-tuberculosis drugs, and basic biochemistry of androgen biosynthesis inhibitors.


We are interested in studying diabetic vasculopathies. Patients with type 2 diabetes mellitus or metabolic syndrome have aggressive forms of vascular disease, possessing a greater likelihood of end-organ ischemia, as well as increased morbidity and mortality following vascular interventions. Our long term research aims to change the way we treat arterial disease in diabetes by:

  • Understanding why arterial disease is more aggressive in diabetic patients, with a focus in redox signaling in the vasculature.
  • Developing targeted systems using nanotechnology to locally deliver therapeutics to the diseased arteries.

My research aims to understand the pathogenesis and host immune response to emerging and re-emerging viral infections, including encephalitic alphaviruses such as chikungunya virus and respiratory coronaviruses such as SARS-CoV-2. Other areas of interest include examination of genetic and environmental factors that influence the response to infection and disease outcome, evaluation of vaccines and novel therapeutics against emerging viruses, and development and optimization of animal models of infectious disease.


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


Research in the Bowers lab focuses on investigation of structure activity relationships and mechanisms of action of natural product-derived small molecule therapeutics. We employ a variety of methods to build and modify compounds of interest, including manipulation of natural product biosynthesis, chemical synthesis, and semi-synthesis. One major area of research in the lab is the rationale engineering of biosynthetic pathways to make bacterial drug factories. Compounds targeting transcriptional regulation of cancer as well as multi-drug resistant venereal infections are currently under investigation in the lab.


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.


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.


Research in the Brouwer laboratory is focused on: (1) hepatic transport of xenobiotics, including mechanisms of uptake, translocation, and biliary excretion; (2) development/refinement of in vitro model systems to predict in vivo hepatobiliary disposition, drug interactions, and hepatotoxicity; (3) influence of disease (e.g., NASH, kidney disease) on hepatobiliary drug disposition; and (4) pharmacokinetics.


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.


The UNC Food Allergy Institute (UNCFAI) was established in 2012 to address the growing needs of children and adults with food allergy. Program investigators study the biologic basis of food allergy in the laboratory and in clinical research studies seeking to better understand the role of allergen-specific IgE and the mechanism of allergen immunotherapy. The Institute provides comprehensive, family-centered patient care for food allergy, food-related anaphylaxis, and other related disorders like atopic dermatitis and eosinophilic esophagitis.


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


Christoffel, Dan
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Publications
PHD PROGRAM
Neuroscience

Dr. Christoffel aims to understand how chronic exposure to particular stimuli (i.e. stress, food, drugs) alters the functioning of specific neural circuits and investigates the mechanisms that regulate these experience-dependent changes. Current studies focus on 1) how experience-dependent plasticity in the nucleus accumbens regulates reward processing, with a focus on the consumption of palatable foods and stress modulation of food intake, and 2) examine the regulatory role of neuromodulators in hedonic feeding.

The ultimate goal of the Christoffel Lab’s research is to understand how adaptive changes in brain function occur and how this can lead to the development of psychiatric disorders. We employ cutting-edge technologies to understand the complex interactions of multiple neural systems that allow us to adapt to our environment and regulate motivated behavior.


My lab in the UNC CEMALB uses translational in vitro and clinical in vivo approaches to investigate how inhaled xenobiotics modify respiratory innate immune responses in people with and without existing lung disease. A central component of my research is the integration of biomedical engineering, additive manufacturing, and advanced cell culture methods to evaluate the health effects of new and emerging tobacco products such as e-cigarettes. I believe the best research is achieved through collaboration across disciplines and welcome interested trainees to contact me to learn more about my lab.


The Cohen Lab investigates how functional brain networks in humans interact and reconfigure when confronted with changing cognitive demands, when experiencing transformations across development, and when facing disruptions in healthy functioning due to disease. We are also interested in how this neural flexibility contributes to flexibility in control and the ability to learn, as well as the consequences of dysfunction in this flexibility. We use behavioral, neuroimaging, and clinical approaches taken from neuroscience, psychology, and mathematics to address our research questions.


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 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.


Our lab studies brain network connectivity in the healthy brain and in neurological and neuropsychiatric patient populations. We focus on the organizational, dynamical, and computational properties of large-scale brain networks and determine how these properties contribute to human behavior in health and disease. We strive to advance the basic understanding of brain structure and function, while making discoveries that can be translated to clinical practice.


Our research focuses on the immunological aspects of pathogen-host interactions. The lab is actively involved in HIV pathogenesis and vaccine studies using the nonhuman primate model of SIV infection. We are particularly interested in pediatric HIV transmission by breast-feeding and the early, local host immune response. A main research focus is on developmental differences in host immune responses between infants and adults and how they alter pathogenesis. The effect of co-infections (e.g. malaria and Tb) on HIV pathogenesis and transmission is a second research focus. The lab is developing a nonhuman primate model of SIV-Plasmodium fragile co-infection to study HIV-P. falciparum infection in humans.


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 work focuses on how air pollutants affect human health, the role of genetics and epigenetic factors in determining susceptibility and clinical/dietary strategies to mitigate these effects. There is a strong emphasis on translational research projects using a multi-disciplinary approach. Thus, by using human in vivo models (such as clinical studies) we validate in vitro, epidemiology, and animal findings.


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.


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


Air pollution exposure is associated with increased hospital visits and mortality, and is a major area of research for the United States Environmental Protection Agency.  The primary research interest of my laboratory is the examination of the effects and mechanisms of air pollutants in the environment on normal cardiopulmonary function (cardiac toxicology), particularly in models of cardiovascular disease, using state-of-the-art targeted and high throughput methods. Research findings are often used to inform environmental public health and contribute to the refinement of the US EPA’s National Ambient Air Quality Standards for specific air pollutants set to limit their health impact.


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.


The broad aim of research in the Fenton Laboratory is to develop and evaluate synthetic drug delivery platforms to treat neurodegenerative disorders in the brain using RNA therapeutics. RNA therapeutics represent a particularly promising class of therapeutics for neurodegenerative management given their ability to tune levels of specific protein expression in living systems. For example, protein downregulation can be achieved by administering short interfering RNAs (siRNAs); alternatively, proteins can be upregulated by messenger RNA (mRNA) administration. Despite this promise, fewer than 0.05% of the world’s clinically approved drugs are RNA therapeutics, and their translation to neurodegenerative disorders in the brain warrants further study at the fundamental and clinical levels.

To address these challenges, our group focuses on the discovery and development of molecular carriers and technology platforms to improve the targeting, safety, and efficacy of RNA drugs within target cells. Specifically, our group leverages an interdisciplinary approach to develop lipid nanoparticles (LNP) as well as soft matter hydrogel platforms that can serve as carrier systems and/or drug delivery models for RNA drugs. Further, our group also explores the development of technological platforms to further expand the potential of RNA drugs within resource limited settings. Lastly, given that mRNA drugs can be engineered to encode for virtually any polypeptide or protein based antigen, our group also aims to leverage our platformable LNP technologies for the study and prevention of cancers and infectious disease. In undertaking such an approach, the goal of our research is to equip students with fundamental skillsets for the development of next generation drugs while simultaneously developing clinically-relevant carrier platforms and technologies for the study, prevention, and treatment of human disease.


Ferguson, Kelly
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Publications
PHD PROGRAM
Toxicology

The Perinatal and Early Life Epidemiology Group conducts research on how maternal exposure to chemicals impacts pregnancy and the development of the fetus and child. We also investigate biological mechanisms of action — such as inflammation, oxidative stress, and endocrine disruption — that connect chemical exposures to adverse birth outcomes.


Fessler laboratory investigates mechanisms of the innate immune response, in particular Toll like Receptor (TLR) pathways and how they regulate inflammatory and host defense responses in the lung.  To this end, we use both in vitro (macrophage cultures) and in vivo (mouse models of acute lung injury and pneumonia) model systems, and also use translational approaches (e.g., studies using human peripheral blood leukocytes and alveolar macrophages).  An area of particular interest within the laboratory is defining how cholesterol trafficking and dyslipidemia innate immunity.


We are inspired by the diversity and complexity found in natural products and use their architecture as both a platform for developing chemical methods and as scaffolds for new molecular tools in chemical biology. We have employed our chemical synthesis skill set to solve emerging challenges facing modern medicine. This has led to ongoing collaborative projects in metastatic cancer, hepatitis C antivirals, dopamine signaling and sigma receptor ligands. Of particular interest is the development of next generation anti-metastasis agents to our recent phase I clinical candidate, metarrestin.


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.


Our goal is to revolutionize the treatment of psychiatric and neurological illness by developing novel brain stimulation paradigms. We identify and target network dynamics of physiological and pathological brain function. We combine computational modeling, optogenetics, in vitro and in vivo electrophysiology in animal models and humans, control engineering, and clinical trials. We strive to make our laboratory a productive, collaborative, and happy workplace.


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.


Over millions of years of coexistence humans and pathogens have develop intricate and very intimate relationships.  These highly specialized interactions are the basic determinants of pathogenesis and disease progression.  Our laboratory is interested in elucidating the molecular basis of disease.  Our multidisciplinary approach to molecular medicine is based on our interest in the translation of basic research observations into clinical implementation.  For this purpose we use a variety of in vitro and in vivo approaches to study AIDS, Cancer, immunological diseases, gene therapy, etc.  Of particular interest is the use of state of the art models such as humanized mice to study human specific pathogens like HIV, EBV, Kaposiâ’s sarcoma, influenza, xenotropic murine leukemia virus-related virus.  In addition, we are interested in the development and implementation of novel approaches to prevent viral transmission using pre-expossure prophylaxis and vaccines.


Dr. Gilmore’s research group is applying state-of–the-art magnetic resonance imaging and image analysis techniques to study human brain development in 0-6 year olds.  Approaches include structural, diffusion tensor, and resting state functional imaging, with a focus on cortical gray and white matter development and its relationship to cognitive development.  Studies include normally developing children, twins, and children at high risk for schizophrenia and bipolar illness.  We also study the contributions of genetic and environmental risk factors to early brain development in humans.  A developing collaborative project with Flavio Frohlich, PhD will use imaging to study white and gray matter development in ferrets and its relationship with cortical oscillatory network development.


Dr M Ian Gilmour is a Principal Investigator at the National Health and Environmental Effects Research Laboratory (NHEERL), U.S Environmental Protection Agency in RTP.    He received an Honors degree in microbiology from the University of Glasgow, and a doctorate in aerosol science and mucosal immunology from the University of Bristol in 1988.  After post-doctoral work at the John Hopkins School of Public Health and the U.S. EPA, he became a Research Associate in the Center for Environmental Medicine at the University of North Carolina. In 1998 he joined the EPA fellowship program and in 2000 became a permanent staff member.  He holds adjunct faculty positions with the UNC School of Public Health and the Curriculum in Toxicology, and at NC State Veterinary School.  He has published over 80 research articles in the field of pulmonary immunobiology where his research focuses on the interaction between air pollutant exposure and the development of infectious and allergic lung disease.


Giovanello, Kelly S.
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Publications
PHD PROGRAM
Neuroscience

My research combines behavioral, patient-based, and functional neuroimaging approaches to investigate the cognitive neuroscience of human learning and memory. My primary research focus is in elucidating the cognitive processes and neural mechanisms mediating relational memory – the form of memory which represents relationships among items or informational elements. In everyday life, relational memory processes play a critical role in linking or binding together the various cognitive, affective, and contextual components of a learning event into an integrated memory trace. I am interested in exploring the cognitive and neural processes mediating relational memory in young adults and examining how these processes change with healthy aging and neurodegenerative disease (particularly Alzheimer’s disease).


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.


My group develops and deploys computational tools to predict physiological function and dysfunction. We are interested in a range of applications in medicine and biology, but our primary focus is the cardiovascular system. My group is actively developing fluid-structure interaction (FSI) models of the heart, arteries, and veins, and of cardiovascular medical devices, including bioprosthetic heart valves, ventricular assist devices, and inferior vena cava filters. We are also validating these models using in vitro and in vivo approaches. We also model cardiac electrophysiology and electro-mechanical coupling, with a focus on atrial fibrillation (AF), and aim to develop mechanistically detailed descriptions of thrombosis in AF. This work is carried out in collaboration with clinicians, engineers, computer and computational scientists, and mathematical scientists in academia, industry, and regulatory agencies.


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


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

Possible Rotation Projects:

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


Imagine a naturally intelligent therapy that can seek out and destroy cancer cells like no other available treatment.  In the Hingtgen Lab, we are harnessing Nobel Prize-winning advancements to create a new type of anti-cancer treatment: personalized stem cell-based therapies.  We use a patient’s own skin sample and morph it into cells that chase down and kill cancer. We take advantage of a little-known aspect of stem cells- they can home in on cancer by picking up a signal through receptors on the cell surface. All the while, the therapeutic stem cells are pumping out potent anti-cancer drugs that selectively kill any cancer cell nearby while leaving the healthy brain unharmed. Our initial studies focused on aggressive brain cancers, however we quickly expanded our testing to a variety of cancer types. Working at the interface of basic science and human patient testing, our ultimate goal is to translate this novel approach into the clinical setting where it can re-define treatment for cancers that currently have no effective treatment options.


Our lab works with adeno-associated viral vectors for both the characterization of vector and host responses upon transduction and as therapeutic agents for the treatment of genetic diseases.  In particular, we tend to focus on the 145 nucleotide viral inverted terminal repeats of the transgenic genome and their multiple functions including the replication initiation, inherent promoter activity, and stimulation of intra/inter molecular DNA repair pathways.  The modification of the AAV ITRs by synthetic sequences imparts unique functions/activities rendering these synthetic vectors perhaps better suited for therapeutic applications.


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


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


Individuals with alpha-gal syndrome, characterized by delayed anaphylaxis (severe allergic reactions) to mammalian meat, have been reported across the globe, yet we have limited understanding of the mechanisms underlying this condition. My lab explores the role of glycolipids interacting with different cells within our innate and adaptive immune systems in the pathogenesis of this allergy. Our vision is to broaden understanding of glycolipids and their role in hypersensitivity disorders. We also want to understand why tick exposure, which is associated with the development of alpha-gal meat allergy, can promote allergic immune responses and how epigenetic dysregulation may influence allergic immune responses. PhD Program: Pathobiology and Translational Science.


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

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

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

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


Research in my lab focuses on the mechanisms by which exposure to air pollutants alters respiratory immune responses and modifies susceptibility to and the severity of respiratory virus infections. Specifically, we are examining the effects of air pollutants such as ozone, woodsmoke and tobacco product exposures on host defense responses and influenza virus infections, using several in vitro models of the respiratory epithelium. In collaboration with physician scientists, we are also translating these studies into humans in vivo.


My research interests and diagnostic responsibilities center around nephropathology and immunopathology. My laboratory carries out basic, translational and clinicopathologic research on kidney diseases. I am most interested in pathogenic mechanisms and pathologic manifestations of glomerular diseases and vasculitis. A major current research focus is on elucidating the pathogenesis of vascular inflammation caused by anti-neutrophil cytoplasmic autoantibodies (ANCA).


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


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

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


Despite recent success in reducing malaria transmission, the estimated annual numbers of malaria infections (~225 million) and deaths (~781,000) remain high. Despite this immense burden, our understanding of the genetic diversity of malaria and the factors that promote this diversity is limited.  This diversity among plasmodial parasites has a critical impact on many factors involved in the control of infections, including: 1) development of drug resistance, 2) development of naturally acquired immunity, and 3) vaccine design.  My laboratory’s primary interests are: 1) describing the genetic diversity of P. falciparum using molecular biological and next generation sequencing tools, and 2) using these data to understand the evolutionary and ecological factors that drive this diversity, promote the emergence of drug resistance and affect our ability to effectively develop immunity.


Kabanov, Alexander (Sasha)
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Publications

In our lab we develop novel polymer based drug delivery systems and nanomedicines incorporating small molecules, DNA and polyptides to treat cancer, neurodegenerative and other CNS-related disorders.


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


Our research explores the role of hypoxia-inducible factor (HIF) in tumorigenesis. HIF is a transcription factor that plays a key role in oxygen sensing, the adaptation to hypoxia and the tumor microenvironment. It is expressed in the majority of solid tumors and correlates with poor clinical outcome. Therefore, HIF is a likely promoter of solid tumor growth and angiogenesis.  Our lab uses mouse models to ask if and how HIF cooperates with other oncogenic events in cancer.  We are currently investigating HIF’s role in the upregulation of circulating tumor cells and circulating endothelial cells.


Our research 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.


Trauma and stress are common in life. While most individuals recover following trauma/stress exposure, a substantial subset will go on to develop adverse neuropsychiatric outcomes such as chronic pain, posttraumatic stress disorder (PTSD), depression, and postconcussive symptoms. Our research is focused on understanding individual vulnerability to such outcomes and to identify novel biomarkers and targets for therapeutic intervention. We use translational research approaches, including bioinformatics analysis of large prospective human cohort data, animal model research, and systems and molecular biology to better understand pathogenic mechanisms. We are particularly interested in the genetic and psychiatric/social factors influencing adverse outcome development, as well as biological sex differences that contribute to higher rates of these outcomes in women vs men.


The Livraghi-Butrico lab is focused on exploring the key determinants of effective airway mucus clearance in health, as well as the consequences of its derangement in muco-obstructive lung diseases. Our lab leverages the unparalleled functional integration offered by in vivo animal models to test mechanistic hypotheses and vet therapeutic options for pre-clinical development.


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 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.


Madden, Michael C.
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Publications
PHD PROGRAM
Toxicology

Exposure to ambient air particulate matter  has been associated with increased human deaths and cardiopulmonary morbidity, such as lung infections and increased asthma symptoms.  I am investigating some types of PM and associated gases  that may be associated with those health effects so  to better regulate or manage the sources of the airborne particles which are identified as playing a role in the adverse health outcomes. I am currently focusing on the effects of diesel exhaust using a variety of approaches ranging from exposing cultured human lung and vascular cells to the exhaust, to studying responses of humans exposed out in traffic.  I am currently designing and implementing testing strategies to assess the toxicity of the future types of vehicular emissions. Additionally some of my research effort attempts to identify what populations are more sensitive to the effects of air pollutants, and the genetic, diet, and environmental reasons behind the increased sensitivity.


Overall goal of our research is to gain better knowledge of gene-gene and gene-environment interactions in common cardiovascular conditions in humans. We have been modifying mouse genome in such a way that resulting mice can model quantitative variations of a specific gene product that occur in human population. With these mice, we explore causes, mechanisms, and nutritional treatments of cardiovascular complications resulted from common conditions such as diabetes, lung infections, and pregnancy-associated hypertension. Current focus is on the oxidative stress and effects of vitamin B12 as antioxidant and beyond.


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


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


Dr. McCullough’s lab takes a translational research approach that incorporates primary cell and organotypic in vitromodels with clinical research (controlled human exposures) to study the role of cellular and molecular mechanisms in mediating the local and systemic effects of exposure to inhaled chemicals.  His laboratory utilizes primary cell/organotypic in vitro models, live cell imaging of fluorescent biosensors, and both traditional and advanced molecular biology/biochemistry methods to characterize the relationship between redox dysfunction/oxidative stress, inflammation, cell signaling pathway activation, epigenetic changes, gene expression, and cell-specific functional outcomes.  In addition to identifying the mechanisms involved in the effects of toxic exposures, Dr. McCullough’s research also aims to identify biomarkers of toxic exposure effects, predicting susceptible populations, and identifying factors that can be used to mitigate adverse exposure outcomes.


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


Our 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 research interests focus on investigating the reparative processes critical to the resolution of acute lung injury. Acute events such as pneumonia, inhalational injury, trauma, or sepsis often damage the lung, impeding its primary function, gas exchange. The clinical syndrome these events can lead to is termed Acute Respiratory Distress Syndrome (ARDS). ARDS is a common pulmonary disease often seen and treated in intensive care units. Despite decades of research into the pathogenesis underlying the development of ARDS, mortality remains high. Our laboratory has built upon exciting observations by our group and others on the importance of how the lung repairs after injury. One type of white blood cell, the Foxp3+ regulatory T cell (Treg), appears essential in resolving ARDS in experimental models of lung injury–through modulating immune responses and enhancing alveolar epithelial proliferation and tissue repair. Importantly, Tregs are present in patients with ARDS, and our lab has found that subsets of Tregs may play a role in recovery from ARDS.


Our research focuses on how environmental exposures impact the development of allergic diseases including asthma and food allergy. We are specifically interested in how exposure to environmental pollutants and immunostimulatory molecules (adjuvants) influence allergic sensitization. The goals of our laboratory are to: (1) define the key environmental adjuvants within the indoor exposome that promote allergic sensitization; (2) characterize the molecular mechanisms by which environmental adjuvants and pollutants condition lung antigen presenting cells to induce allergic immune responses; and (3) identify biomarkers of environmental adjuvant exposure that are associated with increased risk for allergic sensitization in children. Through these research endeavors, we hope to identify potential therapeutic targets for environment-mediated allergic diseases, as well as environmental interventions to mitigate the risk for allergic disease development.


The main goal of the Nagarajan lab research program focuses on how the innate branch of the immune system regulates adaptive immunity, as it relates to the pathogenesis of autoimmune disease such as lupus or rheumatoid arthritis (RA)-induced cardiovascular disease.   IgG-Fcgamma receptor (FcgR)-mediated signaling is critical for mediating host defense against infectious disease, but they also mediate disease pathology in autoimmunity and atherosclerosis. Specifically, we are studying the role of IgG-Fcgamma receptor (FcgR) signaling network in innate immune cells activation that contributes to autoantibody production and T cell subset activation associated with autoimmune, and cardiovascular diseases.  We are using a repertoire of relevant knockout mouse and humanized FcgR mouse models to address the questions of how FcgR-mediated signaling promotes autoimmune disease-induced atherosclerosis. As a translational component, we are collaborating with rheumatologists and cardiologists to analyze changes in innate and T cell subsets in patients with lupus or RA, who has premature atherosclerosis.


The Nguyen lab develops the next generation of effective and safe biotherapeutics for life-threatening diseases such as cancer and myocardial infarction. We engineer novel immunomodulatory carriers based on genetically encoded materials and lipids that home to the site of disease, respond to changes in the microenvironment, and effectively deliver nucleic acids and drugs.


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.


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.


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.


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


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.


Our lab is broadly interested in utilizing high resolution 3D printing to develop novel drug delivery carriers for the treatment of cancer and infectious diseases. Current research interests lay in manufacturing biodegradable porous hydrogel scaffold implants for cell/drug delivery for the treatment of recurrent brain cancer. We are actively investigating biomaterial properties for passive cell/drug loading into scaffolds as well as developing materials and methods to support conjugation strategies for actuated release mechanisms.


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


Many diseases of the kidney remain poorly understood. My research program spans a range of disciplines (e.g., genetics, cell biology, immunology) and experimental approaches (e.g., microscopy, molecular biology, biochemistry, and model organisms—Drosophila and zebrafish) to answer fundamental questions regarding the genetic and cellular basis of kidney function and disease. We are also developing novel assays to study autoimmune diseases of the kidney, with the goal of facilitating patient diagnosis and treatment. By applying modern tools to long-standing problems, we hope to translate our research findings to improved patient outcomes.


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

We have three particular goals:

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

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.


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.


Research in my lab focuses on investigating sex specific effects of air pollutants and new and emerging tobacco products on respiratory immune health. Specifically, the Rebuli lab is examining how the interaction of sex (genetic and hormonal) and toxicant exposure can alter respiratory health. As the majority of research has been historically conducted in men, male animals, or male-derived cell culture models, there is a paucity of information on female respiratory health and sex differences in the effects of toxicant exposure. We are working to fill this knowledge gap by better understanding the role of genetic and hormonal sex on respiratory health. This is particularly important in understanding the development of sex-biased diseases, where men or women are more susceptible to disease development after environmental exposures, such viral infection, asthma, and chronic obstructive pulmonary disease (COPD). We are interested in toxicants such as ozone, wood smoke, cigarette smoke, and e-cigarette aerosols. We investigate effects at both the individual and population level by using clinical (observational clinical studies and prospective exposure trials) and translational (in vitro and ex vivo cell culture) models of the respiratory immune system.


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


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.


Savoldo, Barbara
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Publications

My research interests are in the immunology and pathogenesis of Epstein-Barr virus (EBV) associated lymphomas developing in immunosuppressed patients. I have studied the use of EBV specific cytotoxic T-cells (CTLs) for therapy of post-transplant EBV-associated lymphoproliferative disease (PTLD). I am also interested in the preclinical development of cancer immunotherapy approaches for hematological and solid tumors, specifically by using T cells as platform for exploring genetic immune-manipulations to redirect them to tumors by transgenic expression of alpha-betaTCRs or of chimeric antigen/tumor-specific receptors (CARs). My research also focus on gene modifications aimed at improving the homing of T cells to tumor cells , improving their proliferation and persistence and finally overcoming  the inhibitory effect of the tumor environments, including effects of regulatory T (Treg) cells.


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.


The Shaikh lab aims to understand how differing dietary fatty acids regulate outcomes associated with immunity and metabolism in the context of obesity, type 2 diabetes, and cardiovascular diseases. The lab conducts studies at the human level and in mouse models.  We are currently focused on the mechanisms by which omega-3 fatty acids improve chronic inflammation and humoral immunity upon viral infection in obesity. We are also elucidating how select fatty acids disrupt the biophysical organization of the inner mitochondrial membrane of differing cell types and thereby respiratory activity.


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.


Dr. Shih is the Director of Small Animal Magnetic Resonance Imaging (MRI) at the Biomedical Research Imaging Center. His lab has implemented multi-model MRI techniques at high magnetic field to measure cerebral blood oxygenation, blood flow, blood volume, and oxygen metabolism changes in preclinical animal models. Dr. Shih’s lab is also developing simultaneous functional MRI (fMRI) and electrophysiology recording techniques at high spatial resolution to elucidate the pathophysiological mechanisms of neurovascular diseases. They will apply these techniques to (i) explore/validate functional connectivity network and neurovascular coupling in the rodent brain, (ii) study tissue characteristics after stroke, and (iii) investigate deep brain electrical stimulation, optogenetic stimulation, and pharmacogenetic stimulation in normal and Parkinsonian animal models.


Projects involve the study of cellular and molecular events involved in autoimmunity, and development and application of genetic vaccines to prevent and treat autoimmunity and cancer.


Research in my laboratory focuses on the cardiovascular effects of air pollution and other environmental pollutants in human, animal, and in vitro models, as well as the dietary interventional strategies to mitigate the adverse health effects of air pollution exposure. We are currently conducting two clinical studies to investigate the cardiopulmonary effects of air pollution exposure, and to determine whether dietary omega-3 fatty acids can mitigate the air pollution-induced health effects in human volunteers. These studies provide good training opportunities for students who are interested in training in clinical and translational toxicology research.


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 are interested in understanding how autoreactive B cells become re-activated to secrete autoantibodies that lead to autoimmune disease.  Our research is focused on understanding how signal transduction through the B cell antigen receptor (BCR) and Toll Like Receptors (TLR) lead to secretion of autoantibodies in Systemic Lupus Erythematosus (SLE).


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


My research interests are focused on mechanisms associated with altered innate immune functions, which lead to dysregulated adaptive immunity. Currently my research program has three major arms integrated through with a central philosophy. Specifically, our laboratory focuses on the contribution of epithelial cell biology and signaling to innate and adaptive immune homeostasis and dysfunction. We study the contribution of what I term ‘epithelial cell innate immune (dys)function’ to three major disease conditions: pancreatic cancer, type 1 diabetes (autoimmunity), and periodontal disease (autoinflammation). While appearing to be a diverse research program, we have found that many of the mechanisms and systems in play are surprisingly (or maybe not so surprisingly) similar allowing for rapid translation of our findings. Importantly, previous investigations into the role of epithelial cells in immunobiology have been hindered by a lack of robust primary cell culture techniques, which our laboratory has been able to overcome using both animal and human tissues. Thus, using our novel and unique tools we are able to evaluate our findings in the human conditions, again making translation of our findings that much more feasible. In addition to my primary research objectives, my collaborative research programs, have allowed me to be involved, at some level, in investigating the basic biology of health, multiple autoimmune conditions, autoinflammation, sepsis, and exercise induced inflammation I have been blessed with the opportunities to couple my passions and expertise with that of others to bring together multiple research communities with the goal of advancing human health and hope to be able to continue to do so for years to come.


Social behavior is composed of a variety of distinct forms of interactions and is fundamental to survival. Several neural circuits must act in concert to allow for such complex behavior to occur and perturbations, either genetic and/or environmental, underlie many psychiatric and neurodevelopment disorders. The Walsh lab focuses on gaining an improved understanding of the biological basis of behavior using a multi-level approach to elucidate the molecular and circuit mechanisms underlying motivated social behavior. The goal of our research is to uncover how neural systems govern social interactions and what alterations occur in disease states to inform the development of novel therapeutics or treatment strategies.

One of the major focuses of the Walsh lab is on understanding how genetic mutations, as well as experience, lead to circuit adaptations that govern impaired behavior seen in mouse models of autism spectrum disorders (ASD). Our systems level analysis includes: 1) modeling these disorders with well described genetic markers, 2) defining causal relationships between activity within discrete anatomical structures in the brain that are critical to the physiology of the symptom under investigation (e.g. sociability), 3) performing deep characterization of the physiological profiles of these circuits and using that information to target specific receptors or molecules that may not have been considered for the treatment of specific ASD symptoms.


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.


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


Early life and adult pain can have drastic effects on neurodevelopment and overall quality of life. In the Williams’ Pain, Aging, and Interdisciplinary Neurobehavioral (P.A.I.N.) Lab, our research focuses on behavioral neuroscience and the mechanisms of neurobiology and neurophysiology of pain processing, with a special emphasis on the neonatal. The ultimate research goal is to better understand, recognize, and alleviate pain in the newborn to improve the quality of life in adulthood by uncovering new assessment tools and interventional strategies. Our research interests include the mechanisms of neurobiology and neurophysiology of pain processing, neonatal pain, chronic pain, neurobehavior, osteoarthritis, translational medicine, anesthesia/analgesics, and evoked and non-evoked pain assessment tools. The P.A.I.N. Lab has both pre-clinical and clinical studies to help close the gap in translation.


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.


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.


Our lab studies lipid signaling pathways that are involved in development and diseases by developing novel chemical probes and technologies. As key components of cellular membranes, lipids also serve as signaling molecules and modify functions of proteins through either covalent or non-covalent interactions. Dys-regulation of lipid signaling has been correlated with various diseases including cancer, diabetes, and neurodegenerative diseases. Consequently, many lipid-related proteins or processes have been used as therapeutic targets. However, lipids are dynamically metabolized and transported, making it difficult to illustrate the roles of lipids in development and diseases with limited availability of probes and technologies for lipid studies. The active projects in the lab include: 1) develop novel technologies to synthesize complex lipids, particularly phosphatidylinositides, and identify their interacting proteins in live cells; 2) develop new small molecule sensors and inhibitors for lipid metabolic enzymes such as PI3K and PLC; and 3) investigate cellular functions of lipids on different processes, particularly those regulated by small GTPases.