NIH/NIDDK T32 DK007202
07/01/76 - 06/30/17
Roslyn Lara, GI Program Coordinator
The Division's NIH Training Grant was initially funded in 1976. The Division has trained numerous local gastroenterologists in San Diego as well as developed several academicians at University-based medical schools, including some with leadership and administrative positions.
The aim of the research training program is to develop independent investigators who will devote their career to research on fundamental aspects of digestive diseases and train individuals from the adult and pediatric GI programs.
The Training Grant supports, per year:
- Four Postdoctoral Trainees (MD or PhD) (3 Adult GI and 1 Pediatric GI)
- Two Predoctoral Trainees that will lead to a PhD degree
The grant funds two years of a Gastroenterology Research Fellowship training slot. A training slot is comprised of two research years and one clinical year.
Postdoctoral training involves two years of supervised, self-directed laboratory research aimed at developing the trainee's ability to formulate meaningful scientific questions and hypotheses, design and conduct experiments to test hypothesis, and present results in oral and written form. Laboratory research is performed in the laboratory of faculty sponsors of the Training Grant and supplemented, as appropriate, by didactic course work.
The predoctoral program for PhD candidates involve research training within the laboratory of a faculty sponsor under the auspice of the Biomedical Science Graduate Program.
The training faculty includes basic scientists at UCSD as well as neighboring research institutes where there is close collaboration. The program is designed for graduate students and MD or PhD candidates who are committed to an academic career in digestive sciences. Special efforts are made to attract minority candidates. At completion, postdoctoral trainees are competitive for entry level independent funding and predoctoral trainees are highly competitive for outstanding postdoctoral positions.
Research performance sites include UCSD, VA San Diego Healthcare System (VASDHC), La Jolla Institute for Allergy & Immunology (LIAI), Burnham Institute, and The Salk Institute. A list of the Training Grant faculty sponsors are listed below.
TRAINING GRANT FACULTY SPONSORS
Sheila E. Crowe, MD - UCSD
Dr. Crowe's research program explores the interaction of luminal contents including microbes with the gastrointestinal mucosa that can lead to inflammatory disease and associated epithelial cancer. She focuses on the role of oxidative stress in modulating host responses to bacteria, antigens, and inflammatory processes and examining the multi-functional regulatory protein, AP endonuclease-1 as it regulates epithelial cell responses. Her general approach has been to study signaling events in cultured cell lines and to validate the models using human tissues. As a clinician-scientist gastroenterologist, she has been active in basic, translational, and clinical research. She has supervised many MD trainees, undergraduates, and 6 postdoctoral PhD fellows and roughly half of these individuals are working as academic physicians and research scientists.
Kim E. Barrett, PhD - UCSD
Dr. Barrett's interests involve epithelial transport and barrier function in human health and disease and its inter- and intra-cellular regulation. The laboratory has a primary focus on chloride secretory mechanisms in the gastrointestinal tract. Ongoing studies are characterizing intracellular signaling events intrinsic to the epithelium that limit calcium-dependent chloride secretion. Dr. Barrett's work uses a broad range of techniques from molecular approaches and studies in cell lines to work using animal models or human tissue specimens. All projects in the laboratory are available for trainee participation. Trainees are assigned an independent area, in consultation with Dr. Barrett, and then plays an integral role in matters of experimental design, conduct of the research program, and preparation of findings for presentation in both written and oral formats. Dr. Barrett has considerable experience in hosting trainees and has an active program of lab meetings and informal journal clubs that facilitate communication among lab members and develop presentation skills.
David Broide, MD - UCSD
Dr. Broide's laboratory studies the role of eosinophils in diseases such as asthma and eosinophilic esophagitis. Studies of eosinophilic esophagus are performed in a mouse model of egg-induced eosinophilic esophagitis which is associated with eosinophilic inflammation of the esophagus and remodeling of the esophagus. The use of mutant mice lacking single genes or neutralizing antibodies allows dissection of the role particular genes or gene products play in the pathogenesis of eosinophilic esophagitis.
John Chang, MD - UCSD
Dr. Chang's overall research interests are in the determination of lymphocyte fates during immune responses to microbes. Studies focus on the differentiation of CD4+ and CD8+ T lymphocytes using various animal models of infectious disease as well as models of intestinal inflammation. Approaches used to address these experimental questions include cell culture, flow cytometry, confocal microscopy, gene expression analysis, proteomic approaches, and in vivo experimental models. Trainees will learn and develop expertise in basic immunology and mucosal immunology.
Hilde Cheroutre, PhD - LIAI
Dr. Cheroutre's research focuses predominantly on the biology of intra-epithelial lymphocytes (IEL), their development and function, and in understanding regulatory mechanisms involved in controlling differentiation and regulation of T cells migrating and residing in the intestinal mucosa. The ultimate goal of her research is to understand the biology of mucosal TCRab T cells that provide controlled protection without self-destruction. Trainees have the opportunity to design and execute experiments in vitro and in vivo that understand the function of the IELs.
Mario Chojkier, MD - VASDHC
Dr. Chojkier studies the response to liver injury. Hepatic stellate cell activation causes excessive liver fibrosis resulting in cirrhosis. His laboratory has been investigating whether RSK-inhibitory peptides would block stellate cell activation and liver fibrosis. Trainees would further investigate the molecular pathways responsible for the activation of caspase 8 by C/EBPb-Ala217 as well as the optimal peptide-mimetic compounds for inhibition of stellate cell activation in liver fibrosis.
Edward Dennis, MD - UCSD
Dr. Dennis' laboratory focuses on understanding the regulation of lipid regulation second messengers and signal transduction processes and especially the role of various phospholipases in their generation. Dr. Dennis' laboratory also designs and synthesizes chemical inhibitors of phospholipase A2. The laboratory utilizes organic synthetic approaches, enzyme kinetics, molecular biology, site-specific mutagenesis, cell and tissue culture, and high-resolution NMR techniques, as well as traditional biochemical approaches in attacking phospholipase and membrane problems. Trainees will be involved in one or more of these projects, will be closely mentored, and will learn organic synthetic approaches, enzyme kinetics, molecular biology aimed at site-specific mutagenesis, tissue culture, and high resolution NMR techniques as well as traditional biochemical approaches to attack phospholipase and membrane problems.
Pieter C. Dorrestein, Ph.D.- UCSD
Dr. Dorrestein's lab aims to develop new mass spectrometry-based methods to link biological, including disease and health phenotypes to the underlying chemistry and genotypes. Training in the lab aims to mentor in the molecular analysis of complex molecules and develop tools to translate the chemical language between cells. The lab is extremely well equipped to train individuals in the latest tools for molecular analysis.
Lars Eckmann, MD - UCSD
Dr. Eckmann's overall research interests are in the cellular and molecular pathogenesis of infections with enteric pathogens and the mechanisms underlying the regulation of intestinal inflammation. Studies focus on the use of animal models of intestinal infection and inflammation, and employ molecular, microbiological, and histological approaches to elucidate the key genes and cellular and molecular mechanisms that govern intestinal host defenses against enteric pathogens and regulate inflammatory responses in the gastrointestinal tract. Current studies define host defense mechanisms against the protozoan pathogen Giardia and the bacterial pathogen Escherichia coli and Salmonella. Trainees will have an opportunity to learn in vivo approaches for studying host interactions with microbial pathogens.
Peter Ernst, DVM, PhD - UCSD
The general research interests are in the area of comparative (human to mouse) mucosal immunology with specific projects in immune-epithelial cell interactions involved in the microbial pathogenesis of acute and chronic diseases of the gastrointestinal tract. One area examines the role of adenosine in the development of gastrointestinal Th cells that control inflammatory responses to infections including Helicobacter spp. These infections are relevant to gastroduodenal disease and inflammatory bowel diseases. They also stimulate chronic inflammation that contributes to cancer. We have extended these studies to examine the role of adenosine in the control of disease associated with food- or waterborne pathogens as well as the role of the microbiota on acquired regulatory T cell development. The second area of investigation examines the fate of apoptotic cells. A major part of this project is characterizing the signaling events subsequent to the attachment of an apoptotic cell and to study the impact on host responses when an infected, dead cell is engulfed. These studies have identified a novel pattern recognition receptor for the engulfment of Gram-negative bacterial that is also being characterized.
Marilyn Farquhar, PhD - UCSD
Dr. Farquhar's research focuses on identification of components of G-protein mediated signaling pathways controlling membrane trafficking along the exocytic and endocytic pathways. Dr. Farquhar's laboratory has identified several new proteins that are components of novel G protein mediated signaling pathways. Dr. Farquhar's laboratory uses the two hybrid system and affinity chromatography to identify and characterize novel proteins that interact with GTP-binding proteins and specific regions of resident Golgi proteins. Students in Dr. Farquhar's laboratory select and plan their project in an area of active ongoing laboratory investigation. Graduate students and postdoctoral trainees have the opportunity to learn and develop their expertise in cell biology in a superb teaching environment.
Ariel Feldstein, MD - UCSD/Rady Children's Hospital
The Feldstein laboratory studies the molecular and biochemical pathways leading to the metabolic complications of obesity. Dr. Feldstein is primarily interested in the mechanisms attracting professional phagocytes to obese adipose tissue, as well as the events that link excessive accumulation of lipids in the liver (hepatic steatosis) to liver injury, fibrosis and carcinogenesis. Moreover, he is working to discover novel non-invasive biomarkers for early diagnosis and monitoring of metabolic dysregulation, hepatic steatosis and liver damage. His lab utilizes an array of mass spectrometry-based approaches (LC/ESI/MS/MS, proteomics) directed toward these translational studies. The goal is to use these discoveries to develop safe and efficacious diagnostics and therapeutic strategies for patients with these highly prevalent and potentially serious conditions. To this end, Dr. Feldstein is actively involved in the development of preclinical, translational and clinical research protocols for a number of non-invasive tests and therapeutic agents. The Feldstein's lab offers a unique environment for training of fellows with a focus on translational research.
Theodore Friedmann, MD - UCSD
The Friedmann Laboratory continues its studies of the neuro-developmental disease Lesch Nyhan disease. They are concentrating on microarray and proteomic characterization of human fibroblasts derived from LND patients and of affected brain regions of the HPRT gene knockout mouse model of the disorder. The Friedmann laboratory is also continuing its major study of the molecular mechanisms of growth enhancement by the growth factor IGF-1 in cultured cells and in mice in vivo. Training opportunities for pre- and post-doctoral trainees are in the area of gene therapy working with Dr. Friedmann directly or in collaboration with other training faculty.
Richard L. Gallo, MD, PhD - UCSD
Dr. Gallo's laboratory is interested in understanding the basic mechanisms of epithelial defense and repair. The major focus is in investigating the function and regulation of antimicrobial peptides. Through the use of a variety of biochemical and molecular techniques they have found that the skin produces catatonic peptides during the early response to injury. Another interest of the group is the function of tissue glycosaminoglycans as immune signaling molecules and co-factors to aid in wound repair. Dr. Gallo's group has an active journal club and seminar series as part of its educational program. Trainees will have the opportunity to work on projects involving innate defense molecules relevant to epithelial cell defense using in vitro and in vivo systems.
Pradipta Ghosh, MD - UCSD
Dr. Ghosh's laboratory studies the cell biology of signal transduction with a special emphasis on identification and characterization of signal amplification switches that drive key cellular processes such as migration, proliferation, survival, apoptosis, secretion, etc. In most cases, while timely and restricted amplification of signals is essential to tide over stress injury in physiologic conditions (such as promote healing in any epithelial wounds/ulcers), sustained enhancement/amplification of signals (in response to growth factors/agonists) heralds oncogenesis and cancer metastasis. Similarly, abnormal signal amplification is a key feature during an overzealous inflammatory response during wound healing and can be associated with yet another undesired outcome, i.e., fibrogenesis (cardiac fibrosis after myocardial infarction, all causes of liver cirrhosis, pulmonary and renal fibrosis); thereby distorting normal anatomy and impairing normal functions. Dr. Ghosh's laboratory seeks to gain insights into how incoming signals are amplified in an unrestricted fashion to drive the key cellular processes (secretion, autophagy, growth,proliferation, migration) in health and disease, and identify novel signal-amplification switches/interfaces within key signaling pathways which can also serve as therapeutic targets. Students, technicians, and postdoctoral trainees in Dr. Ghosh's laboratory receive close training and guidance in any area of active ongoing laboratory investigation they wish to follow. The opportunities to gain expertise, learn, discover, and have fun in the process are limitless.
Samir Gupta, MD - UCSD/VASDHC
Dr. Gupta's work focuses on the prevention and screening of colorectal cancer and polyps. Dr. Gupta is the leader of two large-scale comparative effectiveness randomized trials of strategies to boost colorectal cancer screening rates among the underserved as well as numerous observational studies of the clinical and molecular epidemiology of digestive system cancers and neoplasia, including colorectal, hepatocellular, and pancreatic cancers.
Christopher K. Glass, MD, PhD - UCSD
Dr. Glass' laboratory investigates the mechanisms by which sequence-specific transcription factors regulate the development and function of macrophages. A major focus is on members of the nuclear receptor, AP-1 and its families of transcription factors. The laboratory uses a combination of biochemical, cellular, and in vivo model systems and incorporating macrophage-specific knockouts, microarray technologies, and bioinformatic approaches to unravel the contributions of specific factors to the development of specialized macrophage functions and the pathogenesis of inflammatory diseases.
Samuel Ho, MD - VASDHC
Dr. Ho's research programs include both clinical and basic science investigations. Clinical programs include investigations in the treatment and management of chronic hepatitis C and chronic inflammatory conditions of the stomach and intestine. Dr. Ho is the Director of the Minneapolis/San Diego Hepatitis C Resource Center (HCRC). This is one of four centers in the VA system dedicated to developing best practices for patients with hepatitis C and to provide training and education for clinicians working with hepatitis C patients. Dr. Ho continues as Director of the Minneapolis Hepatitis C Resource Center and expanded the program to include San Diego. For future trainees, both the laboratory and clinical hepatitis C center are ideal environments to nurture GI trainees for a future academic career in gastroenterology. In the laboratory, trainees will learn general molecular biology techniques, cell culture, cell cloning, and transfection, gene sequencing, flow cytometry, animal models as well as learning about basic gastrointestinal epithelial biology and the effects of acute and chronic inflammation. The clinical hepatitis C center is staffed by a number of outcomes research personnel and there are numerous clinical projects to become involved with.
Hal M. Hoffman, MD - UCSD
A main focus of Dr. Hoffman's laboratory is the identification of genes for rare inherited disorders. The laboratory identified CIAS1, a gene that is responsible for three autosomal dominant inflammatory disorders. The discovery led to a novel effective treatment for these patients. The laboratory currently investigates the normal function of this gene in human monocytes and genetically modified mice. Also studies on identification of the gene for a rare autosomal recessive diarrheal disease, congenital tufting enteropathy. Trainees will learn a multitude of genetic techniques, as well as determine functional aspects of found genes.
Paul Insel, MD - UCSD
Dr. Insel's laboratory is involved in studies of signal transduction in epithelial cell systems, in particular, by G protein coupled receptors (e.g. P2Y and prostanoid receptors). Work in the laboratory emphasizes MDCK cells, which possess both P2Y and prostanoid receptors as do biliary duct epithelial cells and various other gastrointestinal tract epithelial cells. Other work in the laboratory focuses on the ability of P2Y and adenosine receptors to regulate leukocyte function, especially as related to inflammatory stimuli. Trainees who wok in the Insel laboratory will investigate cellular and biochemical mechanisms involved in the regulation and activation of GTP binding proteins, adenylyl cyclase, phosphodiesterases, protein kinases, including stoichiometry of expression of components in signaling microdomains. Other work involves regulation of adenylyl cyclase isoforms, studies of mechanisms involved in "cross talk" for signal transduction systems (e.g. adenylyl cyclase via Ca2+, nitric oxide and protein kinase C) and by different classes of G protein coupled receptors. The laboratory uses molecular biological, cell biological, and biochemical techniques for its studies. Trainees will select a project that will entail exposure to multiple experimental approaches and methods. Trainees participate in all educational and intellectual activities of the laboratory, including weekly research conferences and a signal transduction journal club.
Michael Karin, PhD - UCSD
The Karin laboratory studies potentially pharmacologically regulated signaling pathways. The laboratory has several generated mouse models, both general and tissue-specific for which to characterize the importance of the inflammatory cascade. Dr. Karin has also produced transgenic mice that express a degradation resistance mutant of NF-kB in various cell types. Dr. Karin also studies the signaling pathways leading from the TNF and IL-1 receptors to activation of various MAP kinases, including JNKs and p38. Trainees are able to participate in studies on the function of these kinases in various inflammatory and immune responses, as well as in mucosal inflammation and epithelial and lamina propria immunocyte biology. Trainees will be able to participate in Dr. Karin's studies of the IkB kinases and their role in inflammatory and autoimmune diseases and cancer.
Richard Kolodner, PhD - UCSD
Dr. Kolodner's laboratory is interested in the genes and proteins that function in genetic recombination, DNA repair events that act in genetic recombination and in overall maintenance of genome stability. Their ongoing projects include the use of the yeast,
Saccharomyces cerevisiae, to study the genes and proteins that function in recombination and repair, the establishment of mutant mice that are defective for DNA repair, the study of the genetics of hereditary nonpolyposis colon cancer (HNPCC), and other cancer susceptibility syndromes that result from DNA repair defects. Trainees have been major participants for many of these projects and are involved in all aspects of the research.
Mitchell Kronenberg, PhD - LIAI
Dr. Kronenberg studies the TCR diversity of the donor derived T cells in the intestine of the diseased SCID recipients by immunoscope (CDR3 length) analysis and sequencing of TCR beta chains. Current experiments explore the roles of Ig family and TNF family costimulatory molecules. Students have the opportunity to work closely with Dr. Kronenberg in selecting and designing their project and an opportunity to learn state-of-the-art molecular and in vivo animal model approaches to study important questions relevant to mucosal inflammation. LIAI maintains an excellent seminar and journal club program that emphasizes graduate and postdoctoral training.
Rohit Loomba, MD - UCSD
Dr. Loomba's research focuses on all aspects of nonalcoholic fatty liver disease including aging, epidemiology, genetic and environmental predisposition, natural history, and treatment of nonalcoholic steatohepatitis (NASH). His research interests also include liver and aging epidemiology as well. Dr. Loomba's vision is to establish a comprehensive center of excellence in clinical research and epidemiology of liver disease at UCSD. He utilizes diverse epidemiologic and outcomes research methodologies to answer clinically relevant questions. The types of research conducted include patient-oriented clinical research based upon patients seen in the liver clinic, clinical trials, population-based cohort studies, twin studies with Dr. Daniel O'Connor, and clinical decision making by utilizing meta-analytic approaches. He continues to work in close collaboration with his colleagues at the NIH, where he received his clinical and research training in advanced hepatology. Dr. Loomba is conducting research on the epidemiology of viral hepatitis in relation with hepatocellular carcinoma. He has established collaborations with the epidemiology group at the National Taiwan University, Taipei, Taiwan where he works closely with his trainees and has several published and ongoing research projects with residents and fellows.
Ravinder Mittal, MD - UCSD
The research performed in Dr. Mittal's laboratory focuses on two areas: (1) esophagus and (2) pelvic floor. With regards to the esophagus, physiology, and pathophysiology of esophageal motor disorders and visceral sensation is being evaluated using novel methodologies. Physiologic, pharmacological, and clinical studies are being conducted to answer the questions related to pathophysiology of esophageal motor disorder and esophageal sensation. The techniques being utilized to answer these questions are pressure recordings, electrical signal recordings, ultrasound imaging, isolated muscle strip preparation, and immunohistochemistry studies of the neurotransmitters of the GI tract. Some of these studies are being conducted in humans and other studies in animals. Dr. Mittal explores new methods of studying esophageal motility that utilizes high frequency ultrasound probes. His laboratory is also exploring the physiology and pathophysiology of pelvic floor function. For these studies, physiologic monitoring and various types of imaging is being done in human and animal models to understand the physiologic and pathophysiologic role of puborectalis muscle in fecal and urinary continence. Trainees will have the opportunity to develop a project within these areas of study and will actively participate in all the educational aspects of this laboratory.
Eyal Raz, MD - UCSD
The Raz laboratory analyzes the interaction of innate immunity with microbial agents. In particular, studies of the role of microbial products in the activation and inhibition of mucosal inflammation. They have characterized the immune profile induced by TLR ligands, such as LPS, lipopeptides or bacterial DNA at mucosal sites, and analyzed the impact of these ligands on experimental colitis (e.g. DSS-, TNBS-, and oxazolone-induced colitis). Future projects will identify the mechanisms behind these diverse effects and its relationships to health and disease states. His laboratory offers excellent projects and an exciting environment for postdoctoral trainees with an interest in learning and applying state-of-the-art approaches to translational science.
Robert Rickert, PhD - Burnham Institute
The Richert laboratory focuses on normal and aberrant B lymphocyte function. A major effort in the laboratory is to utilize conditional gene targeting in mice as well as signal transduction and cell culture approaches to characterize the key intracellular signaling pathways (e.g. PI3-kinase and NF-kB) that direct B cell differentiation. From these efforts, they have gained insight into the molecular underpinnings of selected B cell malignancies and autoimmune conditions. Of particular interest is understanding the cellular and molecular events that govern the germinal center response, resulting in the generation of high affinity memory B cells or antibody-producing cells. Studies in this area address IgM versus IgG signaling coreceptor (CD19, CD21, FcgRIIB) function and cytokine receptor signaling. Since B cells are generally non-adherent cells, they are also interested in understanding the molecular basis of B cell homing to particular in vivo niches. There are training opportunities available in all of the outlined areas. Trainees will acquire technical expertise in molecular and cellular immunology, signal transduction, and working with mouse models of human disease as they relate to understanding autoimmunity and lymphomagenesis. Trainees participate in weekly lab meetings and journal clubs, as well as local and national meetings.
William Sandborn, MD - UCSD
Dr. Sandborn's overall research interests are in clinical trials, clinical pharmacology, and measurement of disease activity in inflammatory bowel disease. Studies focus on randomized controlled trials, clinical pharmacology and therapeutic drug monitoring biologics, and use of endoscopy, MRI enterography, and histology to measure disease activity. Trainees will have the opportunity to learn about the development of instruments to measure endoscopic, radiographic, and histologic disease activity.
Jeffrey Schwimmer, MD - UCSD
Dr. Schwimmer's research focuses on the field of pediatric obesity. Dr. Schwimmer's research addresses why do obese children differ so greatly in the number, type, and severity of co-morbid conditions? Obesity is a major risk factor for nonalcoholic fatty liver disease (NAFLD) in children and because of the high prevalence of childhood obesity it has become the most common cause of chronic liver disease in children. Students and trainees working in the Schwimmer laboratory are able to participate in local and national studies. Current projects include studies of (1) quality of life in NAFLD, (2) the association of NAFLD and cardiovascular events, (3) dietary risk factors for NAFLD, and (4) adipocytokines in obesity and fatty liver.
Susan S. Taylor, PhD - UCSD
Dr. Taylor uses a multi-disciplinary approach to probe the structure and function of one of the simplest members of the protein kinase family, cAMP-dependent protein kinase (cAPK). Dr. Taylor is studying the dynamic properties of PKA in the cell using recombinant and fluorescence methods. Trainees will learn state-of-the-art molecular biology to understand the structure and function of protein kinases.
Ajit Varki, MD - UCSD
Dr. Varki's research interests are focused on a family of sugars called the sialic acids and their role in biology, evolution, and disease. Sialic acids are found at the outermost position of the glycan chains of all vertebrate cell surfaces and glycoproteins. The highest levels are found in the nervous system. Active projects are relevant to the roles of sialic acids in microbial infection, the regulation of the immune response, the progression of cancer, and unique aspects of human evolution. Trainees have the opportunity to work with in vitro and in vivo models to understand the function of sialic acids.
Geoffrey Wahl, PhD - The Salk Institute for Biological Studies
Dr. Wahl's studies center around the mechanisms that ensure faithful reproduction and segregation of DNA and how such safeguards are abrogated during cancer progression. A major focus concerns the mechanisms by which the p53 tumor suppressor ensures the integrity of the genome. Over the past several years, Dr. Wahl devised strategies to investigate how these extrachromosomal molecules are transmitted to daughter cells at mitosis. Dr. Wahl's laboratory at The Salk Institute offers a number of areas for projects by trainees that will provide excellent training in basic mechanisms of cell growth regulation directly relevant to gastrointestinal neoplasia.