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.
Our research focuses on understanding the biology and pathogenic mechanisms of mycobacterial pathogens, including Mycobacterium tuberculosis, the bacterium responsible for tuberculosis (TB) disease. TB remains a significant world health problem that is responsible for 1.5 million deaths annually and drug resistant TB is an increasing problem. We additionally study nontuberculous mycobacteria (NTM), which are emerging pathogens responsible for chronic pulmonary infections in individuals with underlying lung diseases such as cystic fibrosis or chronic obstructive pulmonary disease. We also investigate novel strategies to treat mycobacterial infections that include anti-mycobacterial drugs delivered as aerosols and bacteriophage therapy.
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.
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.
The immune system of severely burned patients becomes extremely suppressed after injury. An overwhelming number of patients die from wound infection and sepsis. However, we are unable to graft these patients with skin from other donors as their immune system is still able to reject the graft efficiently. Our inability to cover the wound site leaves the patients further open to bacterial and fungal infections. Our laboratory investigates the translational immune mechanisms for these devastating consequences of burn within mouse models and burn patients. Focuses in the lab include 1) investigation of innate molecule control of both the innate and adaptive immune systems after burn injury, 2) Role of innate signaling to Damage Associated Molecular Patterns in Immune Dysfunction after burn / inhalational injury,focusing on mTOR-mediated Immunomodulation 3) Using NRF2/KEAP1-Targeted Therapy to Prevent Pneumonitis and Immune Dysfunction After Radiation or Combined Burn-Radiation Injury and 4) Investigating sex-specific disparities in Immune Dysfunction after trauma / transplantation.
Developing and applying novel mass spectrometry (MS)-based proteomics methodologies for high throughput identification, quantification, and characterization of the pathologically relevant changes in protein expression, post-translational modifications (PTMs), and protein-protein interactions. Focuses in the lab include: 1) technology development for comprehensive and quantitative proteomic analysis, 2) investigation of systems regulation in toll-like receptor-mediated pathogenesis and 3) proteomic-based mechanistic investigation of stress-induced cellular responses/effects in cancer pathogenesis.
Cross-talk between insulin like growth factor -1 and cell adhesion receptors in the regulation of cardiovascular diseases and complications associated with diabetes.
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.
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.
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.
Our research focuses on understanding the molecular and cellular mechanisms of leukocyte (white blood cell) trafficking and homing in vascular inflammation and immune responses. We are interested in the glycobiology of the Selectin leukocyte adhesion molecules and their ligands, and understanding the roles for these glycoproteins in the pathogenesis of inflammatory/immune cardiovascular diseases such as atherosclerosis and vasculitis. We are also interested in the mechanisms whereby the selectins and their ligands link the inflammatory response and coagulation cascade and thereby modulate thrombosis and hemostasis.
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.
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).
My research aims at prevention and treatment of cardiovascular diseases and focuses on the identification of genes that confer susceptibility or resistance to the diseases with the use of genetically engineered mice. In collaboration with Dr.Oliver Smithies, I very recently developed a new method for altering gene expression by modifying 3’ untranslated regions in mice which enables fine-tuned modification of gene expression. I am now analyzing the phenotypes of several mouse models generated with this method.
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.
My research goals are to identify the mechanisms by which environmental factors regulate smooth muscle cell phenotype and to define the transcriptional pathways that regulate SMC-specific gene expression.
The 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.
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 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.
My research interests include the role of von Willebrand factor in thrombosis and atherosclerosis. Our current lab work focuses on the molecular biology of porcine von Willebrand factor.
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
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.
Our long term goals are to better define mechanisms of chronic intestinal inflammation and to identify areas for therapeutic intervention. Research in our laboratories is in the following four general areas: 1) Induction and perpetuation of chronic intestinal and extraintestinal inflammation by resident intestinal bacteria and their cell wall polymers, 2) Mechanisms of genetically determined host susceptibility to bacterial product,. 3) Regulation of immunosuppressive molecules in intestinal epithelial cells and 4) Performing clinical trials of novel therapeutic agents in inflammatory bowel disease patients.
The Serody laboratory focuses on tumor and transplant immunology studies using both animal models and translational work with clinical samples. We have performed pioneering work in both of these areas. Our laboratory was the first to describe a role for migratory proteins in the biology of acute GVHD. We were the first group to use eGFP transgenic mice generated in part by our group to track the migration of donor cells after transplant. This work showed a critical role for lymphoid tissue in the activation of donor T cells. Most recently we have been the first group to demonstrate the absence of ILC2 cells in the GI tract after all types of transplant and we have generated novel studies into the ILC2 niche in the bone marrow. For our tumor work we were one of the first groups to use genomic evaluations of the tumor microenvironment to characterize the immune response in cancer models. We were the first group to demonstrate how to enhance checkpoint inhibitor therapy in triple negative breast cancer models and have been one of the leading groups in performing genomic evaluations using TCGA data. Finally, we are one of the leading groups in the world characterizing the role of B cells in the anti-tumor immune response.
Cell Biology & Physiology
Our lab has two areas of interest: the molecular basis of liver diseases and the biochemical mechanisms of disorders linked to intermediate filament gene mutations. We use biochemical, cell-based and in vivo approaches to identify potential disease targets and to understand their function and regulation. The major goal of our work is to promote the discovery of pharmacological agents that can slow or halt the progression of these diseases.
Cell Biology & Physiology
A critical component of airways innate defense is the thin liquid layer lining airway surfaces, the periciliary liquid (PCL), that provides a low viscosity solution for ciliary beating and acts a lubricant layer for mucus transport. Normal airways appear to be able to sense the PCL volume and adjust ion channel activity accordingly. The long term goal of this laboratory is to understand how homeostasis of PCL volume occurs in airway epithelia under normal and pathophysiological conditions. Currently, research in the Tarran lab is focused on three main areas: 1) Regulation of epithelial cell function by the extracellular environment, 2) Gender differences in cystic fibrosis lung disease and 3) The effects of cigarette smoke on epithelial airway ion transport. We utilize cell biological and biochemical techniques coupled with in vivo translational approaches to address these questions.
The goal of our research is to identify signaling mechanisms that contribute to normal and pathophysiological cell growth in the cardiovascular system. We study cardiac and vascular development as well as heart failure and atherosclerosis.
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.
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.
Cell Biology & Physiology, Genetics & Molecular Biology, Oral & Craniofacial Biomedicine, Pathobiology & Translational Science
Interest areas: Developmental Biology, Cell Biology, Cancer Biology, Stem Cells, Genetics
PhD programs: Pathobiology & Translational Sciences, Genetics & Molecular Biology, Cell Biology & Physiology, Oral Biology, Biology
Tissue development and homeostasis depend on the precise coordination of self-renewal and differentiation programs. A critical point of regulation of this balance is at the level of cell division. In the Williams lab, we are interested in stratified epithelial development, stem cells, and cancer, with a particular interest in how oriented cell divisions contribute to these processes. Asymmetric cell divisions maintain a stable pool of stem cells that can be used to sustain tissue growth, or mobilized in response to injury. However, dysregulation of this machinery can lead to cancer, particularly in epithelia where tissue turnover is rapid and continuous. Using the mouse epidermis and oral epithelia as model systems, we utilize cell biological, developmental and genetic approaches to study the molecular control of oriented cell divisions and mitotic spindle positioning, and how division orientation impacts cell fate choices in development, homeostasis, injury, and disease.
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.