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 email@example.com and Elisabeth Rogers at firstname.lastname@example.org. 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.
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.
Ramon A. Bataller, M.D., Associate Professor, Medicine (GI) and Nutrition (School of Public health) and his group have been studying the mechanisms of alcoholic liver disease. Dr. Bataller´s research current research focuses on the molecular mechanisms of alcoholic hepatitis in order to identify new targets for therapy. Dr. Bataller is the overall PI of an NIH-funded international consortium to study alcoholic hepatitis (InTeam). Moreover, he belongs to the Bowles Center for Alcohol Studies. In the last years, Bataller´s team has identified several molecular driers of alcoholic hepatitis that can represent new targets for therapy (i.e. osteopontin, Fn14, CCL20, CXC chemokines). Moreover, they have developed the first histological classification of alcoholic hepatitis (AHHS). Currently, Dr. Bataller´s efforts are focused on identifying molecular signatures in patients with alcoholic hepatitis that predict response to therapy. He is building a large biorepository of livers from patients with alcoholic hepatitis linked with clinical data. By performing RNA deep sequencing and kinome analysis, Bataller´s team is trying to develop a molecular classification of these patients that can be used for a personalized medicine.
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 timehonored 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.
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.
J. 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.
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. His current work explores the influences of the IBD risk allele NOD2 on the intestinal microbiota. Using a NOD2 knockout mouse model, he is examining the effects of NOD2 deficiency on bacteria such as Faecalibacterium prausnitzii and Escherichia coli that have been implicated in the pathogenesis of human IBD. He is also studying possible mechanisms of this dysbiosis, such as alterations in antimicrobial peptide function in the NOD2-deficient mice. Finally, from a translational standpoint, he is assessing levels of relevant bacteria, particulary Faecalibacterium prausnitzii, Escherichia coli and Segmented Filamentous Bacteria in human tissue samples obtained from patients with different IBD genotypes and phenotypes. His hope is to identify patterns of dysbiosis in various subsets of IBD patients that will ultimately lead to patient-specific therapies for these disorders.
Jonathan J. Hansen, M.D., Ph.D., Assistant 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 is dissecting these interactions using gnotobiotic IL-10-/- mice that develop chronic, immune-mediated colitis when selectively colonized with certain commensal bacteria such as E. coli NC101. He has shown that intestinal inflammation triggers NC101 to upregulate bacterial stressresponse genes, which help bacteria tolerate heat stress and potentially lethal levels of reactive oxygen species (ROS) such as those found in the inflamed intestine and macrophage phagolysosomes. He hypothesizes that the host inflammatory milieu upregulates bacterial stress response genes, 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. Ultimately, these studies have the potential to reveal novel host-microbial interactions that could be targeted for therapeutic purposes.
Susan J. Henning, Ph.D., Professor, Medicine (GI) (Co-Director T32, Advisory Committee) is working to identify and characterize intestinal stem cells (ISC). The project is relevant to this training program because ISC play a central role in the ability of the small bowel to respond to various traumas such as resection, radiation, chemotherapy damage, etc. Although the presence of ISC has been inferred for many years, to date they have proven very difficult to isolate. Dr. Henning and colleagues have deployed a novel sorting approach in order to collect a “side population” of putative ISC and profiled the gene expression of this cell fraction by microarray. These studies together with high throughput in situ hybridization analyses identified new ISC markers which are being used to develop improved methods of isolation. Dr. Henning is currently exploring both in vivo graft models and in vitro culture models to assess the capacity of different ISC preparations for proliferation and differentiation. Ultimately the isolation and transplantation techniques developed in this project should have two applications: a) new therapies for various conditions in which the intestine is damaged; and b) use of the intestine as a site for gene therapy.
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 (appointment 5/1/10) is a physician-scientist who is focused broadly on the molecular pathogenesis of acute and chronic hepatitis in humans due to hepatitis C virus (HCV) and hepatitis A virus (HAV). His research lies at the interface of molecular virology, innate immunity, inflammation and disease pathogenesis. His primary research interests include the molecular mechanisms by which these two hepatotropic viruses replicate their positive-strand RNA genomes, and how these viruses are recognized by host innate immune sensors. Dr. Lemon’s research aims to define how these viruses have evolved to evade innate antiviral defenses in the liver, and how these events influence the subsequent development of virus-specific adaptive immunity. Recent work has revealed how the HCV NS3/4A serine protease disrupts RIG-I and TLR3-mediated activation of IRF-3 and NF-κB, and how antiviral protease inhibitors counteract these effects. Recently, Dr. Lemon has discovered that two distinct processing intermediates of the HAV 3Cpro cysteine protease, 3ABC and 3CD, similarly disrupt interferon signaling, and is now interested in determining how these viral evasion tactics relate to the disparate outcomes of these two intra-hepatic virus infections. A parallel focus in his laboratory has been the interaction of HCV with cellular tumor suppressor proteins, including in particular the retinoblastoma tumor suppressor Rb, and how such virus-host interactions contribute to cell cycle dysregulation and hepatocellular carcinogenesis in chronic hepatitis C. A related focus of ongoing research is the interaction of HCV with the liver specific micro-RNA miR-122, itself a tumor suppressor, and the mechanism underlying HCV dependence on miR-122 for efficient genome amplification.
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). The Miao lab studies how the innate immune system tells the difference between pathogenic bacteria as compared to bacteria that do not encode significant virulence factors. We have focused on the cytosolic sensors because many pathogens attempt to access the cytosolic compartment, either by toxins, type III secretion systems, or wholesale cytosolic invasion. Amongst cytosolic sensors, the inflammasomes trigger IL-1b and IL-18 secretion as well as a unique form of cell death called pyroptosis. We previously demonstrated that pyroptosis is an innate immune defense mechanism in vivo, and are currently studying the molecular mechanisms in triggering this response. We showed that the NLRC4 inflammasome specifically detects the activity of type III secretion systems, and this permits detection of Salmonella typhimurium in the intestinal tract. However, S. typhimurium evades inflammasomes when it spreads systemically, which is a critical virulence trait; if S. typhimurium triggers inflammasome-dependent pyroptosis, it becomes avirulent. We have also found that caspase-11 specifically responds to cytosolic bacteria, and that this provides protection in vivo against cytosolic bacteria such as Burkholderia thailandensis and B. pseudomallei. However, hyperactivation of caspase-11 on a systemic level leads to sepsis and death.
John F. Rawls, Ph.D., Associate Professor, Department of Molecular Genetics and Microbiology, Duke University, studies the vast and complex community of microorganisms (gut microbiota) that exerts a profound influence on our biology. The mechanisms by which gut microbes regulate distinct aspects of host biology are largely unresolved, and represent potential therapeutic targets for promoting and preserving human health. The overall objective of his research program is to exploit the transparency and genetic manipulability of the zebrafish to elucidate the mechanisms underlying evolutionarily-conserved host-microbe interactions in the intestine. The presence of a gut microbiota in mice results in a significant increase in body fat, caused by increased microbial digestion of dietary nutrients, and microbial suppression of intestinal transcription of Fasting-induced adipose factor (Fiaf/Angptl4). He finds that the zebrafish microbiota similarly stimulates nutrient digestion and suppresses fiaf expression in the intestinal mucosa. He is using transgenic reporter assays to identify discrete cis-regulatory elements at the zebrafish fiaf locus that mediate expression and microbial suppression in the intestinal epithelium. To facilitate testing the role of the zebrafish gut microbiota on fat storage, he has developed novel methods for visualizing zebrafish adipogenesis in vivo, and is using these methods to analyze zebrafish adipose tissue development as a function of microbial status. He has also identified individual bacterial species (e.g., Pseudomonas aeruginosa) that can recapitulate the effect of the normal microbiota on intestinal fiaf suppression. Efforts are now underway to test P. aeruginosa gene function on zebrafish fiaf expression. This knowledge would provide insights into the foundations of host-microbial mutualism in the intestine, and new strategies to control Fiaf levels and energy storage in humans.
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.
R. 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.
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.