Basic Science Track
The Gastroenterology Basic Science Research Training Program at the University of North Carolina at Chapel Hill is designed to promote the development of promising MD and PhD postdoctoral fellows as independent investigators and future university faculty members who will investigate the pathogenesis of gastrointestinal and hepatic diseases. Training of the postdoctoral fellow is individualized, and the most important component is conducted by the trainee in the faculty mentor’s laboratory. Additional training includes didactic courses, seminars and conferences, and seminars on responsible conduct of research.
The training faculty consists of 23 funded investigators from 11 basic science and clinical departments at the University of North Carolina, who are all full-time members of the NIDDK-funded Center for Gastrointestinal Biology and Disease (CGIBD). These broadly based faculty members have a documented history of close interactions promoting multidisciplinary research. The postdoctoral fellows benefit from the unique strengths of digestive disease research at the University of North Carolina, which include the CGIBD with its research cores, a research-oriented Pediatric Gastroenterology Division, a coordinated research training program, animal models of digestive diseases, outstanding programs in gastrointestinal epidemiology and biostatistics, a Gene Therapy Center, and a Center for Alcohol Studies.
The program is funded by an NIH T32 Training Grant on which R Balfour Sartor, MD serves as Program Director and Susan J. Henning, PhD serves as Associate Program Director. The program recruits 1 to 2 new fellows each year from a pool of MD adult gastroenterology fellows, MD pediatric gastroenterology fellows, PhD postdoctoral fellows, and individuals holding DVM degrees.
For those individuals who wish to apply to our basic science program and who are not pursuing our basic science fellowship program as part of our general MD fellowship program through the Match, please provide CV, one page description of prior research experience, half page explanation of career goals, and three letters of reference including one from your prospective mentor to Dr. Balfour Sartor at firstname.lastname@example.org and Ann Zakaria at email@example.com. This information will be reviewed by our Training Program Advisory Committee. Candidates offered a position will be assigned a primary research mentor. To ensure safe arrival of all application materials, we strongly urge interested individuals to send information electronically.
Minorities are encouraged to apply. To be eligible for Training Grant support, applicants must be U.S. citizens or permanent residents.
Nancy Allbritton, MD, PhD Kenan Professor, Joint Department of Biomedical Engineering and Department of Chemistry. The ability to monitor and control the environment at the cellular and tissue level is one of the most promising applications for microengineered systems. “Organ-on-a-Chip” platforms to provide exquisite control of experimental variables, yet recapitulate much of the physiology of an intact large or small intestine. The lab is pursuing development and application of intestine-on-chip microdevices to recapitulate the microenvironments of the intestine. The group is taking a two-pronged approach in this work. Intestinal stem cells are being grown and their progeny differentiated on a unique scaffold to create a self-renewing 2D surface that re-creates the cellular milieu and function of the intestinal epithelium. This technology is the basis for high-throughput analysis platforms for microbiome studies as well as screening drugs, probiotics and toxins affecting the small and large intestines. We are also developing a 3D scaffold on which isolated stem cells are grown in such a way as to recapitulate the in vivo stem cell environment. Methods to create gradients across the tissues are being developed to mimic the gradients of growth and differentiation factors as well as the other chemical and gaseous gradients thought to exist in the in vivo intestines. These intestinal fluidic chips make it feasible to investigate and control the environment of the intestinal physiology using tissue from genetically engineered mice or from humans for mechanistic studies of the stem cell niche, cancer, immune diseases and other intestinal pathologies.
Janelle C. Arthur, Ph.D., Assistant Professor, Microbiology & Immunology. Our group seeks to understand how inflammation alters the pro-carcinogenic capabilities of the microbiota, with the long-term goal of targeting resident microbes as a preventive and therapeutic strategy to lessen inflammation and reduce the risk of colorectal cancer. Our general approach combines genomics, bioinformatics, immunology, bacterial cultivation techniques and gnotobiotic mouse models to identify inflammatory and pro-carcinogenic bacteria from human patients and uncover mechanisms by which these bacteria promote inflammation and neoplasia. One current project focuses upon clinical strains of intestinal E. coli isolated directly from human inflammatory bowel disease (IBD) patients, who are known to experience a high risk of colorectal cancer. We are evaluating the ability of these resident microorganisms to induce inflammation and tumorigenesis in mouse models and defining functional capabilities, microbial genes and pathways that are causally and mechanistically linked to carcinogenesis. Ultimately this research will uncover novel microbial targets and enable us to manipulate the intestinal microbiota as a therapeutic target for human digestive diseases and cancer.
Anthony Blikslager, DVM, Ph.D., Professor, Surgery and Gastroenterology, School of Veterinary Medicine, N.C. State University explores mechanisms of repair of the small intestinal inter-epithelial tight junction. As a DVM/ PhD, he exposes trainees to the most appropriate models available to answer their hypotheses. Dr. Blikslager trained as a physiologist and combines state of the art molecular and genetic techniques with time honored techniques such as the Ussing chamber. Following initial emphasis on repair of ischemic injury, he has studied other mechanisms of epithelial recovery following events such as stress and chemical injury (bile and acid). Future research plans will include microbial injury and associated inflammation, followed by studies of facilitating repair. Mentoring is augmented by graduate coursework at NC State University in gastroenterology, immunology, cell biology, genetics, and statistics.
Scott J. Bultman, Ph.D., Associate Professor, Genetics investigates the mechanism of how dietary fiber protects against colorectal cancer. Utilizing gnotobiotic mouse models, we are investigating bacterial fermentation of fiber into butyrate, which is the primary energy source of colonocytes and has potent tumor-suppressive effects. We are particularly interested in characterizing its effects as a histone deacetylase (HDAC) inhibitor to epigenetically regulate gene expression. However, butyrate is a pleiotropic molecule, and we are also evaluating the importance of other butyrate-mediated mechanisms in tumor suppression. This includes butyrate inducing Treg cells and having anti-inflammatory properties, improving barrier function, and functioning as a ligand for G protein coupled receptors.
Kathleen M. Caron, Ph.D., Professor and Chair, Cell Biology and Physiology. In the past dozen years, an expanded repertoire of genes and molecular pathways involved in the development of the lymphatic vascular system has been elucidated. However, considering the essential role of lymphatic vessels in intestinal lipid absorption and the increased prevalence of inflammatory diseases of the intestine, it is rather remarkable that there are currently more questions than answers regarding whether and/or how lymphatic vessels contribute to (or may be causative of) pathophysiological diseases in adults. Our research group directly addresses many of these questions by building upon our exciting discoveries on the essential roles of adrenomedullin (AM) signaling in lymphatics. For example, our recent studies have used an inducible knockout allele to show that loss of the adrenomedullin receptor in adult animals fully recapitulates the clinical sequelae related to lymphangiectasia, including dilated lymphatics, reduced intestinal lipid absorption, protein losing enteropathy and limb edema. Current studies build upon these exciting findings and strive to elucidate the physiological and molecular processes that lymphatics play in i) intestinal disease initiation and progression, ii) normal intestinal lipid absorption under a variety of different challenge conditions and iii) the initiation and progression of mucosal injury, inflammation and repair. The elucidation of these molecular pathways may ultimately form the basis of GPCR-targeted approaches for the therapeutic modulation of intestinal lymphatic vessels, particularly during lymphangiectasia and disease conditions associated with digestive tract inflammation.
Ian M. Carroll, Ph.D., Research Assistant Professor, Gastroenterology, School of Medicine (UNC). The goals of my research are to determine the mechanisms through which specific members of the intestinal microbiota influence gastrointestinal physiology, adiposity, and behavior. My laboratory has developed and validated techniques to collect and store biological human and murine samples for microbiological analyses. We have also developed a technique for isolating bacterial DNA from human fecal and colonic mucosal samples. Our research team characterizes the intestinal microbiota in human and murine biological samples and analyzes the resulting data using the Quantitative Insights Into Microbial Evolution (QIIME) pipeline. Our laboratory currently investigates the mechanism(s) by which enteric microbial communities lead to inflammatory bowels diseases (IBD) and adiposity and behavior dysregulation in anorexia nervosa (AN). Our experiments involve (i) collection and storage of human and murine fecal material in an appropriate manner for analyzing the intestinal microbiota; (ii) colonizing germ-free (GF) mice with enteric microbes; (iii) isolating fecal DNA and subsequent characterization of the intestinal microbiota via high-throughput sequencing of the 16S rRNA gene; and (iv) analysis of the resulting enteric microbiota data. Our investigations have the potential to direct how to test adjunct interventions in IBD and AN with pre-, pro-, anti-, or syn-biotics to enhance current approaches to improve treatment outcome in these illnesses.
Rosalind Coleman, MD Professor Nutrition Dr. Coleman’s lab focuses on energy metabolism in knockout mice and in differentiated hepatocytes, myocytes, and fat cells in culture. Her studies include glucose and fatty acid use, responses to insulin, and the effects of physiological stresses like fasting, exercise, cold exposure, and high fat diets. She is particularly interested in the activation of long-chain fatty acids and their partitioning into pathways of complex lipid synthesis versus beta-oxidation. Her laboratory has also cloned and characterized novel glycerol-3-phosphate acyltransferases, the first step in the synthesis on triacylglycerol and phospholipids. Her studies of mice that are deficient in lipid synthetic enzymes has shown the importance of specific isoforms in the development of hepatic steatosis and NASH, diet-induced obesity, and hormonally induced insulin resistance. Recent studies have demonstrated that acyl-CoAs are compartmentalized within cells and that compartmentalization may depend on specific interacting protein partners.
Christopher M. Dekaney, Ph.D., Assistant Professor, Surgery (NCSU) explores mechanisms that control intestinal stem cell proliferative status following damage. Recent improved understanding of how intestinal stem cells are controlled under homeostatic conditions indicate that there is exquisite control of entry and exit of intestinal stem cells into and out of the cell cycle under normal conditions. In contrast, very little is understood about how intestinal stem cells are controlled during intestinal stress such as following surgical resection or mucosal damage. He uses a model of chemotherapy-induced mucosal damage to study the response of intestinal stem cells during epithelial repair. His primary focus is to understand how fibroblast growth factors (FGF) mediate epithelial repair, and specifically what effects these factors have on intestinal stem cells. Expression of FGFs is transiently upregulated during repair and these FGFs can signal through one or more of the four FGF receptors. He uses in vivo and in vitro approaches to delineate the function of two of the FGF receptors (receptors 1 and 2) during repair. In other systems FGF receptor 1 activation promotes increased proliferation while FGF receptor 2- activation promotes cell survival and differentiation. Understanding how these receptors and their ligands function in promoting intestinal epithelial repair has significant clinical implications as both FGF-7 and FGF-10 (palifermin and repifermin, respectively) are used as treatments for chemotherapy-induced mucositis.
Terrence (Terry) Furey, Ph.D., Associate Professor, Genetics. The Furey Lab is interested in understanding gene regulation processes, especially epigenetically controlled processes, and how alterations in the epigenetic landscape contribute to complex phenotypes such as the inflammatory bowel diseases. We have explored these computationally by concentrating on the analysis of genome-wide open chromatin, miRNA, histone modification, and gene transcription 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 work is focused on understanding genetic and epigenetic contributors to Crohn’s disease through our collaboration with Dr. Shehzad Sheikh. This work has included analysis of open chromatin, miRNA, and mRNA expression data in both the IL-10 knockout model of colitis, where we find that chromatin is aberrantly reprogrammed in the gut even in a germ-free environment, and in human colon, where we find two distinct molecular signatures of Crohn’s disease that are associated with distinct clinical phenotypes.
Victor Garcia-Martinez, Professor, Medicine (Infectious Diseases) explores lymphocyte migration into effector tissues like the gut, which is the result of a series of poorly understood but highly complex interactions between cell adhesion molecules, integrins, chemokines, and chemokine receptors. He has investigated the migration of human lymphoid cells into the gastrointestinal tract of immunodeficient mice. Specifically, he uses bone marrow/liver/thymus (BLT) humanized mice. In BLT mice, the bone marrow is reconstituted with human hematopoietic stem cells producing all human lymphoid lineages resulting in systemic repopulation. In addition, bone marrow–derived T cell progenitors are produced that repopulate an implanted human organoid consisting of a piece of autologous fetal liver and thymus resulting in human MHC-restricted functional T cells. Results demonstrate the high degree of compatibility between the mouse and human systems that results in the appropriate repopulation of the mouse gut tissue with human lymphoid cells. For the most part, the reconstituted BLT gut clearly resembles human gut descriptions in the literature. Perhaps the most telling features were the presence of human CD4CD8αα cells, a T cell subset known only to exist in GALT, and the presence of abundant Peyer’s patches in the small intestine and lymphoid follicular aggregates in the large intestine localized with human lymphocytes (T and B), macrophages, and DCs. In addition, human lymphocytes (T and B), macrophages, and DCs are found distributed throughout the effector lamina propria in humanized BLT mice suggesting that these mice have largely “normal human” GALT. Based on the remarkable similarities observed between the GALT of BLT mice and humans, we are in the process of testing humanized BLT mice as a model to study key aspects of human mucosal immunology and GALT development.
Katherine S. Garman, MD, MHS, Associate Professor, Medicine (GI), Duke University, Duke Molecular Physiology Institute – The Garman lab studies mechanisms of injury, repair, and the development of cancer in the gastrointestinal tract. We are particularly interested in the esophagus, where we study the role of the esophageal submucosal glands (ESMGs) as a progenitor cell niche. Much of our work begins with observations in human esophagus; we identified acinar ductal metaplasia (areas of proliferation with a ductal appearance) within human ESMGs in the context of esophageal injury as well as neoplasia. In order to prospectively study ESMGs, which are present in humans but not in mice or rats, we worked closely with the CGIBD large animal core at NC State to develop a porcine model of esophageal injury and repair. We also use 3D culture methods in the lab. Using these models, a current area of focus is the role of gastrin signaling in esophageal repair. We are also interested in the role of microbiota of the upper GI tract in esophageal wound-healing and carcinogenesis. https://sites.duke.edu/garman/
Ajay S. Gulati, M.D., Associate Professor, Pediatrics (GI) is focused on understanding interactions between the commensal microbiota of the gut and the host epithelium, particularly in the context of chronic inflammatory conditions such as IBD. Specifically, he is interested in determining how various susceptibility genes for IBD affect the structure and composition of the intestinal microbiota through their impact on gut epithelial cells such as Paneth cells and intestinal stem cells. As a pediatric gastroenterologist, he is particularly interested on how the development age of the host affects these gut-microbial interactions. Dr. Gulati’s current work explores the impact of host recipient age on gut epithelial and microbial responses to fecal microbiota transplantation. It is his hope that leveraging the relative malleability of the pediatric microbiota will pave the way for microbial modulation strategies to treat pediatric IBD in a minimally-toxic manner.
Jonathan J. Hansen, M.D., Ph.D., Associate Professor, Medicine (GI). A widely accepted hypothesis is that inflammatory bowel diseases (IBD) are caused by overly-aggressive, T cell- mediated immune responses to bacterial products in genetically susceptible hosts. While the host response to bacterial products has been extensively studied, little is known about the subsequent effects of host inflammation on bacterial properties. Dr. Hansen’s overall goal is to determine how host-derived inflammatory factors affect commensal microbial physiology. He hypothesizes that the host inflammatory milieu upregulates bacterial stress response genes in commensal gut bacteria, which in turn allows bacteria to adapt to the environment and perpetuate inflammation by increasing their survival and virulence. He is testing this hypothesis using a variety of in vivo and in vitro approaches aimed at determining mechanisms by which the host communicates with these commensal microorganisms. Specifically, his lab uses the Il10-/- mouse model of spontaneous colitis, gnotobiotic techniques, microbial RNA-Seq, microbial metagenomic DNA-Seq, metabolomic analysis, cultured intestinal epithelial cell monolayers, and ex vivo immune cell stimulation assays. Ultimately, these studies have the potential to reveal novel host-microbial interactions that could be targeted for therapeutic purposes.
Temitope O. Keku, Ph.D., Professor, Medicine (GI). Dr. Keku’s research involves translational research combining basic science with epidemiology to gain a better understanding of the etiology and pathogenesis of colorectal cancer. Her research interests are: genetic and molecular epidemiology of colorectal cancer; assessment of the contribution of genetic and non-genetic factors to colorectal cancer susceptibility; identification of germ-line or tumor characteristics associated with cancer risk and clinical outcomes (response to therapy and survival); identification of novel biomarkers for early detection to define risk groups for prevention; cancer health disparities; understanding the role of gut microflora in etiology of colorectal cancer. She is the lead PI of a NIH funded study investigating the role of the gut microbiota, inflammation and diet in colorectal cancer.
Stanley M. Lemon, M.D., Professor, Medicine (ID), Microbiology & Immunology We study the molecular pathogenesis of acute and chronic liver disease due to infections with hepatitis A virus (HAV) and hepatitis C virus (HCV). We work at the interface of molecular virology, innate immunity, inflammation, and disease pathogenesis. Work in the laboratory has revealed that HAV is released from infected cells in a non-lytic fashion cloaked in host cell membranes, and circulates in the blood of infected humans in a quasi-enveloped form resistant to neutralizing anti-HAV antibodies (eHAV). These seminal observations have blurred classic distinctions between enveloped and non-enveloped viruses, and challenge basic, long-held tenets of virology. Our current research is focused on the mechanisms underlying the biogenesis and release of quasi-enveloped eHAV, and mechanisms of cellular entry for both naked and quasi-enveloped viruses. More generally, we are interested in the molecular mechanisms by which HAV and HCV replicate their positive-strand RNA genomes, how these hepatitis viruses are recognized by host innate immune sensors, and the role of innate immunity in hepatocellular apoptosis and inflammation. We use both cell-culture based and murine models to study how these viruses have evolved to evade innate antiviral defenses in the liver, and how these events shape the subsequent development of liver injury and virus-specific adaptive immunity.
Scott T. Magness, Ph.D., Gastroenterology and Biomedical Engineering, School of Medicine (UNC). Research focus is on elucidating genetic mechanisms underlying stemness and developing translational models to establish a finer understanding of stem cell-driven regeneration dynamics in homeostasis and injury. Using a combination of genetic mouse models and micro-frabricated bioengineered platforms, we are exploiting the self-renewal capacity and multipotency of ISCs to develop long-term ex vivo models of the intestine and colon with primary tissues. These biomimetic models offer new solutions for compound screening and cell-based therapies.
Edward Miao, M.D., Ph.D., Assistant Professor, Microbiology and Immunology (UNC). My lab studies how the how programmed cell death can be used to defend against intracellular infections. Programmed cell death can be initiated by the infected cell itself, or by cytotoxic lymphocytes both in the innate and adaptive immune system. Our interests began with the study of how cytosolic inflammasome sensors detect bacterial pathogens. For example, we showed that NLRC4-caspase-1 detects the activity of the bacterial type III secretion system, whereas caspase-11 detects the LPS shed from Gram-negative bacteria that invade the cytosol. In response, caspase-1 and -11 drive pyroptotic programmed cell death, where the infected cell literally explodes. More recent work has led us to study how natural killer cells and cytotoxic T cells drive programmed cell death to defend against intracellular pathogens. We also have interests in expanding into how other forms of programmed cell death defend against infection, but also may become immunopathologic during inflammatory disease. We study a variety of pathogens that target the gastrointestinal tract, including intestinal pathogens as well as pathogens that are tropic for infection of the liver. We study host adapted pathogens such as Salmonella Typhimurium and Listeria monocytogenes. We also study environmental opportunists that the immune system normally eradicates without a trace, but which can be deadly when immune defenses are absent, such as Burkholderia thailandensis and Chromobacterium violaceum. Our publication record can be found here: https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/43158153/?sort=date&direction=descending
John F. Rawls, Ph.D., Associate Professor, Department of Molecular Genetics and Microbiology, Duke University. Dr. John F. Rawls, Associate Professor of Molecular Genetics and Microbiology, Duke University School of Medicine, studies how the intestine microbiota contribute to host digestive physiology, inflammation, energy balance, and gene expression. His lab uses gnotobiotic, genetic, genomic, and in vivo imaging approaches to determine how commensal microbiota interact with vertebrate hosts, as well as the mechanisms underlying assembly of intestinal microbial communities. He has pioneered the use of germ-free or gnotobiotic zebrafish to investigate the roles of microorganisms in vertebrate biology, and uses complementary zebrafish and mouse models to define key conserved aspects of host-microbiota interaction, providing new insights into underlying molecular mechanisms. https://mgm.duke.edu/faculty-and-research/primary-faculty/john-rawls-phd/
Matthew R. Redinbo, Ph.D., Kenan Distinguished Professor of Chemistry, Biochemistry, Microbiology and Genomics, School of Medicine and College of Arts and Sciences (UNC). Dr. Redinbo’s laboratory studies the roles the microbiota play in health and disease. His research team uses the tools of structural, chemical and molecular biology, as well as in vitro, ex vivo and in vivo systems, to determine how specific GI microbial enzymes affect the treatment of disease, including the efficacy and toxicity of anti-cancer drugs. He also probes the GI microbiome with an eye toward understanding at the mechanistic level how particular substrates affect microbial energy utilization, and, in turn, host physiology. Lastly, his group is designing microbiome-targeted inhibitors that provide precision control over microbial functions, and in this way he is shifting the balance of model systems from unhealthy to healthy. He is PI on several NIH grants to support these projects.
Balfour Sartor, M.D., Distinguished Professor, Medicine (GI), Microbiology & Immunology, T32 Director, investigates mechanisms of gene-environment interactions between susceptible hosts, commensal bacteria and diet using genetically engineered rodents and defined bacterial species under gnotobiotic conditions. These studies investigate the role of endogenous IL-10 from antigen presenting cells in regulating innate and adaptive immune responses to commensal bacteria and mechanisms by which HLA B27 regulates APC and T cell responses to bacteria. He has demonstrated functional differences in various commensal E. coli strains that determine their ability to induce colitis in IL-10-/- mice, is identifying unique genes restricted to colitogenic E. coli strains and is selectively deleting these putative virulence genes in adherent/invasive E. coli to determine which bacterial genes mediate epithelial invasion, persistence within macrophages and induction of colitis. He is investigating mechanisms of intracellular and intraluminal bacterial killing by the host with defective function of NOD2 and IGRM using knockout mice. NOD2 and IGRM-1-mediated killing of luminal bacteria is being investigated by measuring differential expression of various antimicrobial peptides and altered commensal bacteria in KO mice. In addition, he is performing translational research with a consortium of institutions (Washington Univ., Mt. Sinai, U. Chicago, Mass. General, Mayo Clinic, Cedars Sinai) to determine the effect of NOD2 and ATG16L1 polymorphisms on enteric microbial composition in ileal biopsies from normal and Crohn’s disease patients. In addition, Dr. Sartor is investigating mechanisms by which dietary iron, aluminum, sucrose and fructose influence enteric microbiota composition and function and experimental colitis, providing insights that can be readily translated to human investigations.
Shehzad Z. Sheikh, M.D., Ph.D., Assistant Professor of Medicine & Genetics. His research program focuses on the pathogenesis of the Inflammatory Bowel Disease (IBD), Crohn’s disease and ulcerative colitis. In general terms, his laboratory seeks to understand how information is encoded and dynamically utilized in immune cells from healthy and disease prone intestines. They 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. Dr. Sheikh’s group uses 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. Dr. Sheikh’s lab focuses on understanding how these important controllers of inflammation are turned on and off in IBD. They 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.
Natasha T. Snider, Ph.D., Assistant Professor, Cell Biology and Physiology. The Snider group studies the cellular and molecular basis of liver diseases and disorders linked to intermediate filament gene mutations. We use biochemical, cell-based and in vivo approaches to identify disease targets and to understand their function and regulation. Our major goal is to promote the discovery of pharmacological agents that can slow or halt the progression of these diseases. In our liver disease-related work we are investigating the regulation and function of CD73 and a novel splice variant that we identified (CD73S) in mouse and human hepatocytes, liver injury models, and hepatocellular carcinoma. In our intermediate filament-related work we are developing clinically-relevant systems for disease modeling and drug screening for rare orphan diseases.
Rita Tamayo, Ph.D., Assistant Professor, Microbiology and Immunology studies the molecular basis of intestinal colonization by Clostridium difficile and Vibrio cholerae. The mechanisms by which these human diarrheal pathogens interact with the host epithelium, a requisite step in establishing an infection, are poorly understood. The Tamayo laboratory aims to identify bacterial colonization factors that participate in adherence and determine how production of these factors is regulated during infection. In particular, the role of the intracellular signaling molecule cyclic diguanylate (c-di-GMP) in controlling production of candidate adhesins is being explored. Trainees use a combination of bacterial genetic, biochemical, animal modeling and other approaches to carry out this research. Ultimately, the characterization of the colonization mechanisms used by these pathogens may reveal preventive and therapeutic options for C. difficile and V. cholerae infections.
Casey M. Theriot, Ph.D., Assistant Professor, Microbiology and Infectious Disease, NCSU College of Veterinary Medicine My research is multidisciplinary and collaborative, bridging basic research with translational research. My research focuses on exploring the interplay between the gastrointestinal tract microbiota and the pathogen Clostridium difficile, a significant and re-emerging public health problem. C. difficile infection (CDI) is the leading cause of antibiotic-associated colitis, and is responsible for significant morbidity, mortality, and increased healthcare costs. My research has shown that antibiotics disrupt the indigenous gut microbiota reducing resistance to C. difficile colonization. My broad research career goal is to understand the complex interactions among the gastrointestinal microbiota, pathogens, and the host. I am currently focused on characterizing these mechanisms with respect to antibiotic usage. To accomplish my research goals I integrate data obtained from high-throughput methods that analyze the gastrointestinal microbiome, metabolome and host immune responses in animal models and human biological specimens to model these interactions. Currently, we are exploring two mechanisms by which the gut microbiota is able to provide colonization resistance against C. difficile, 1.) the production of secondary bile acids from commensal non-pathogenic Clostridia species, and 2.) competition of nutrients by members of the commensal Clostridia. The goal of this work is to design more targeted bacterial therapeutics for the treatment and prevention of CDI.
Jenny P.Y. Ting, Ph.D., Distinguished Professor, Microbiology & Immunology focuses on the NLR (Nucleotidebinding domain, leucine-rich repeat containing) gene family that represents intracellular sensors of microbial and damage-associated molecular patterns. NLR proteins not only affect host response to pathogen infection, but are also known to affect inflammation and genetically-associated inflammatory disorders, such as Crohn’s disease, thus their impact on gastrointestinal disorders is enormous. Her recent work on the role of the NLR inflammasome on colitis and colitis-associated cancer (J. Exp. Med., epub, April 2010) shows that many more NLR genes are likely to affect gastrointestinal disorders.
The training program is funded by an Institutional National Research Service Award from the NIH. As such, the program abides by the rules established for these awards.
Stipends are established by the NIH. The current annual stipend for postdoctoral trainees is determined by the number of FULL years of relevant postdoctoral experience at the time of appointment. Relevant experience may include research experience (including industrial), teaching, internship, residency, clinical duties, or other time spent in full-time studies in a health-related field following the date of the qualifying doctoral degree.