VERMONT IMMUNOBIOL/INFECTIOUS DIS CTR: CORE A: ADMINISTRATIVE/INTELLECTUAL CORE

佛蒙特州免疫生物学/感染性疾病 CTR：核心 A：行政/智力核心

• 批准号: 7720912
• 负责人: Ralph C Budd
• 金额: $ 104.34万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720912
• 关键词: Advertisements; Advisory Committees; American; Anthrax disease; Applications Grants; Appointment; Area; Arenavirus; Asthma; Attention; Autoimmune Hepatitis; Autoimmune Process; Autoimmunity; Award; Bioinformatics; Biology; Borrelia; Borrelia burgdorferi; CD4 Positive T Lymphocytes; CD8B1 gene; CD94 Antigen; Cardiovascular system; Caspase; Categories; Cell Adhesion; Cell Count; Cell Survival; Cells; Cellular biology; Centers of Research Excellence; Cessation of life; Clinical Trials; Coffee; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Core Facility; Coxsackie Viruses; Coxsackievirus Infections; Cryptosporidium; Cryptosporidium parvum; Cystic Fibrosis; Data Set; Dendritic Cells; Development; Discipline; Disease; Disease susceptibility; Doctor of Medicine; Doctor of Philosophy; Education; Educational Curriculum; Entamoeba histolytica; Epithelial; Evaluation; Extrinsic asthma; Faculty; Family member; Fostering; Foundations; Friends; Funding; Future; Genes; Genus Capra; Graduate Education; Grant; HIV; Hantavirus; Histamine Receptor; Homeostasis; Host Defense; Human; Immune; Immune response; Immune system; Immunity; Immunobiology; Immunologist; Immunology; Infection; Infectious Agent; Infectious Disease Immunology; Inflammation; Institution; Interdisciplinary Study; Interleukin-6; Intestines; Joints; Laboratories; Lassa virus; Latina; Leadership; Ligands; Liver; Lung; Lyme Arthritis; Lymphocytic choriomeningitis virus; MAPK14 gene; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of ovary; Manuscripts; Maps; Mediating; Medical Research; Medicine; Memory; Memory B-Lymphocyte; Mentors; Methods; Microbiology; Mission; Modeling; Molecular; Molecular Biology; Molecular Genetics; Molecular Target; Names; National Institute of Allergy and Infectious Disease; Natural Immunity; Neurosciences; Numbers; Object Attachment; Oklahoma; Outcome; Pathogenesis; Performance; Phagocytosis; Physicians; Plants; Positioning Attribute; Postdoctoral Fellow; Predisposition; Pregnancy; Process; Program Research Project Grants; Proteomics; Publications; Published Comment; Pulmonary Cystic Fibrosis; Reaction; Recruitment Activity; Regulation; Research; Research Institute; Research Personnel; Research Project Grants; Resources; Role; Running; Science; Scientist; Series; Signal Pathway; Signal Transduction; Societies; Source; Stress; Structure; Students; Study Section; Systemic Lupus Erythematosus; T memory cell; T-Cell Activation; T-Lymphocyte; TLR2 gene; TLR3 gene; Thymectomy; Time; Toll-like receptors; Toxoplasma gondii; Training; Transgenic Mice; United States National Institutes of Health; Universities; Up-Regulation; VDJ Recombinases; Vaccine Design; Vaccines; Variant; Vermont; Virginia; Virulence; Virus; Visit; Week; Woman; Work; Writing; Y Chromosome; college; cytokine; day; expectation; fighting; fungus; high throughput analysis; immunoregulation; interest; interleukin-17C; interleukin-21; killings; lecturer; macrophage; member; microbial; morin; novel strategies; pathogen; plant defensin proteins; programs; response; scavenger receptor; skills; synergism; tumor; vaccine evaluation; ward

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Administrative Core Program Summary and Evaluation Overall Structure The Administrative Core has several missions, including overall organizational and scientific leadership, careful mentoring of the junior investigators, recruitment of new faculty, initiation of a seminar series in Immunology/Infectious Diseases, organizing COBRE retreats, and support of graduate students and postdoctoral fellows in COBRE laboratories. Progress on each of these areas is detailed below. Our current COBRE faculty include: Junior Faculty ¿ Jonathan Boyson, Ph.D. Molecular Determinants of iNKT Cell Activation by CD1 and Its Ligands ¿ Beth D. Kirkpatrick, M.D. Innate Immune response to Cryptosporidium parvum ¿ Christopher Huston, M.D. Entamoeba Histolytica Phagocytosis and Inflammation. ¿ Mariana Matrajt, Ph.D. Subversion of Host Signaling by Toxoplasma gondii. ¿ Terrence Delay, Ph.D. Regulation and Effectors of Plant Innate Immunity Senior Faculty -Ralph C. Budd, M.D. - PI -Gary Ward, Ph.D.  Co-PI -Elizabeth Bonney, M.D. -Sally Huber, Ph.D. -Mercedes Rincon, Ph.D. -Cory Teuscher, Ph.D. -Markus Thali, Ph.D. Core Facilties Faculty Advisors -Proteomics and mass spec.  Dwight Matthews, Ph.D. -Microarray and Bioinformatics  Jeffrey Bond, Ph.D. Of note is that the junior faculty contain two women, two physician/scientists, and one Latina. Furthermore, the three infectious agents studied by the junior investigators in this proposal are Category B (Cryptosporidium parvum, Entamoeba histolytica, and Toxoplasma gondii) on the NIH/CDC list of Priority on the NIH/CDC list of Priority Pathogens. The newest junior faculty member, Dr. Terrence Delaney, comes from the Department of Plant Biology as he works on plant defensins, which are very similar in structure and signaling to mammalian Toll-like receptors. Dr. Delaney replaced Dr. Gustavo Pedraza. As a result, the faculty now come from seven departments distributed among three colleges within the University, very much consistent with the interdisciplinary intent of COBRE grants. At an organizational level we initiated a weekly joint laboratory meeting at which all COBRE investigators and their laboratory students/postdoctoral fellows would present their work-in-progress. This now brings together for the first time faculty from the disciplines of immunology, infectious diseases, microbial pathogenesis, and plant defense for a weekly venue at which to share our research. As director I have intentionally stressed the overlapping interests of the microbiologists and immunologists over common themes. The reason for this is not only the obvious realization that the immune system is present primarily to fight infection, but also that the most interesting and important breakthroughs in cell biology have almost always occurred at the interface between disciplines. From this initiative comes the very clear expectation that these collaborative interactions will result in collaborative R01s, a new P01 Program project Grant application, and an expanded number of training slots on our T32 Training grant (currently only 2 slots funded). The areas of overlap have included the contributions of bacterial products in triggering Toll-like receptors (Borrelia burgdorferi triggering of TLR2, Drs. Budd and Teuscher; Coxsackievirus triggering of TLR3, Dr. Huber, and plant defensins, Dr. Delaney), NOD family members (Entemeba triggering of caspase-mediated death of macrophages, Dr. Huston, and anthrax killing of macrophages via Nalp1b by Dr. Teushcer), CD1 triggering of NKT cells (Drs. Boyson and Bonney), and HIV, Borrelia and Cryptosporidium triggering of gd T cells (Drs. Thali, Budd, and Kirkpatrick). A closely related effort has been renewed interest in factors that influence immune memory, in anticipation of vaccine design as a logical outcome of our collaborative efforts. Specific signaling pathways in this area include the four histamine receptors (Dr. Teuscher's group has identified upregulation of H3R only on memory T cells), IL-6 promotion of IL-21, a B cell memory cytokine (Dr. Rincon), and caspase regulation of effector T cell survival (Dr. Budd). These themes have been incorporated into a competitive renewal application of our 9-year P01 Program Project Grant. A third research theme that has begun to attract our attention is the possibility of autoimmune reactions as a result of the response to infectious agents. These have included the role of NKT cells in autoimmune hepatitis, given the co-localization of CD1d expression and resident NKT cells in the liver (Dr. Boyson), how dysregulated T cell homeostatic proliferation during pregnancy (Dr. Bonney) or in the absence of Fas (Dr. Budd) might augment autoimmune diatheses, and the influence on the number of CD4+CD25+ Treg by either Coxsackievirus infection (Dr. Huber) or day 3 thymectomy (Dr. Teuscher). In the spirit of fostering new interdisciplinary research efforts, we have conducted two types of COBRE retreats. Last year we held a retreat (or "advance" as I have renamed it) that focused on "challenge talks" in which investigators intentionally proposed new models and hypotheses that involved two or more COBRE laboratories. This format was very well received among the COBRE faculty and staff/students and has actually launched several new pilot collaborations. (In my capacity as Associate Chair of Medicine for Research, I organized as departmental research day last week that used a similar format, which the faculty found refreshingly different and stimulating). The second interactive COBRE retreat was just held on March 26, 2008 as an joint 4-way COBRE meeting between the lung and immunology COBRE programs at UVM and the two equivalent COBRE programs at Dartmouth. We called this the COBRE Quadrille and this also brought together, perhaps for the first time, 4 regional COBRE programs to establish new collaborations, and ways to potentially combine core resources to enhance performance. The program from this meeting is included below. COBRE Quadrille Meeting Dartmouth/UVM March 26, 2008 MedEd Center 200 (Case Methods Auditorium) 9:30 Coffee and goodies 9:45-9:50 WELCOME & GOALS of the meeting: Chair-Budd 9:50-10:30 OVERVIEW of the QUAD COBRE Program Budd, Green, Irvin, Stanton 10:30-11:30 CELL ADHESION/INFECTION: Chair-Budd Brent Berwin, Ph.D. "Exposing and Exploiting Scavenger Receptors in Immune Processes" Christopher Huston, M.D. "Mechanism of Entamoeba histolytica phagocytosis" 11:30-12:30 CANCER: Chair-Green Scott Gerber "Candidate-centric searching: a novel approach for high throughput analysis of proteomics datasets" Jose Conejo-Garcia, M.D./Ph.D "Re-programming anti-tumor immune responses by targeting dendritic cells in the ovarian cancer microenvironment" 12:30-1:30 Lunch 1:30-2:40 ASTHMA: Chair-Irvin Richard Enelow, M.D.: "Inhibitory NK cell receptor regulation of CD8+ T cell responses" Matthew Poynter, Ph.D. "Airway epithelial-targeted strategies for immune modulation of allergic asthma" Jonathan Boyson, Ph.D. "Widespread variation in NKT cell number and function predicts shared susceptibility to NKT-mediated disease" 2:40-3:00 Break 3:00-4:00 CYSTIC FIBROSIS: Chair-Stanton Laurie Whittaker, M.D. "CD4 T Cells in CF Lung Disease: Friend or Foe?" Sophie Moreau-Marquis, Ph.D. "Cystic Fibrosis Talk" 4:00-4:30 CORE RESOURCES & OPPORTUNITIES Short Presentations by appropriate COBRE lecturers 4:30-5:30 ROUNDTABLE: Chair-Irvin Next steps, collaborations We have continued our COBRE seminar series in Immunology/Infectious Diseases. We have invited investigators who, for the most part, are studying the immune response to infectious agents. The list of speakers to date includes: 8/2/07: Eleftherios Mylonakis Virulence of human pathogenic fungi Harvard 9/14/07: Casey Weaver Th17 Immunity with Infection UAB 9/21/07: Christopher Hunter Inhibiting Induction of Infection/Inflammation U Penn 10/15/07: Mark Schlissel Regulating V(D)J Recombinase UC Berkeley 11/11/08: You-Wen He Caspases in T cell Activation Duke 3/14/08: David Artis Th17 cells and intestinal homeostasis U Penn 3/28/08: Laurent Brossay NKT cell development Brown 5/2/08: George Tsokos Molecular targets in SLE Harvard 5/23/08: Randy Noelle Autoimmunity therapies Dartmouth Evaluation We met with our External Advisory Committee (EAC) in October, 2007 for the first of our annual meetings with the EAC. The format for this retreat was the traditional presentation of each research project by the five junior investigators, the two core facilities, with an overview presentation by the director (Dr. Budd) and Co-Director (Dr. Ward). Our EAC members include Dr. Roger Davis (UMass), Dr. Eric Pamer (Sloan Kettering), Dr. William Petri (U. Virginia), and Alan Sher (NIH). Dr. Pamer could not make that meeting. As an ex-officio EAC member, I have asked Dr. Donald Capra to attend in the future. Dr. Capra is former director of the Oklahoma Medical Research Foundation, and is the PI of the COBRE grant there in Immunology. His expertise in running a highly successful COBRE program will be highly valuable to us. The review of our EAC is included. At the global level, their remarks included many laudatory comments regarding the synergism of the group, the importance of the theme, and the leadership. Two institutional items needed attention. The first was that the COBRE program had not yet received its assignment of laboratory space for new faculty recruits. However, this has not inhibited the pace of new faculty recruitment as both the Departments of Medicine and Micriobiology and Molecular Genetics have kindly offered laboratory space. The second issue was the need for greater access to graduate students, particularly by the junior faculty. This should be resolved as we launch our new Umbrella Program, which contains a new track exclusively for Immunology/Micriobiology. New Faculty Recruitment We are in the midst of a recruitment effort for three new faculty to join the COBRE team in the Vermont Center for Immunology/Infectious Diseases. To attract the very best applicants, we decided to post the advertisement for the three faculty positions in the same advertisement. This would allow us to highlight the fact that this represents a significant recruitment effort to launch a new center. Getting approval for three new tenure track positions and for simultaneous recruits at a small institution such as UVM took some time and effort, but was eventually approved by the Provost. We now have our first new recruit, Dr. Jason Botten, arriving from Scripps Research Institute on July 1, 2008. Dr. Botten is an expert in the study of arenaviruses (hantavirus, lassa virus, LCMV) and is mapping immunodominant epitopse of these viruses in humans for eventual vaccine design. A second finalist is returning shortly for a second visit. Education In the area of education we have begun two initiatives. The first is a new graduate education track in Immunology/Microbiology as part of UVM's new umbrella program in Cell and Molecular Biology. This is a direct result of the critical mass of investigators in this area that now exist at UVM, a direct result of the COBRE grant. As part of this initiative, we are developing a new curriculum for graduate students in this track. We will offered the first UVM credited graduate seminar in advanced immunology this past year and will continue that. In collaboration with the Vermont Lung Center COBRE, we offered joint seminar series in grant writing, laboratory management skills, and transgenic mice. Finally, we have continued to provide funding for three senior graduate students, Ms. Aoife Heaslip in Dr. Ward's laboratory, Mr. Rajkumar Noubade in Dr. Teuscher's laboratory, and Ms. Ketki Hatle in Dr. Rincon's laboratory. Mr. Noubade recently successfully defended his thesis and will move off the COBRE grant, and be replaced by a new senior graduate student. Additional areas of accomplishment have been made in publications, including 14 from junior faculty and 43 from senior faculty. Among these, Dr. Rincon just had a manuscript accepted to Science that describes a new function for p38 in phosphorylating GSK3b. Grants by junior faculty now include an R01 to Dr. Boyson, and a Young Investigator's Award to Dr. Huston from the American Society for Clinical Investigation. Dr. Kirkpatrick was one of two finalist in a large center grant application to NIAID to be designated an NIH vaccine testing center. Although her group was not the final winner, to have been one of two finalists was enormously helpful to get her name known at NIAID. As a result of this recognition, Dr. Kirkpatrick was invited to join a vaccine center grant renewal application being submitted by Johns Hopkins. Among senior faculty, Dr. Budd received a 5-year renewal of his R01 grant studying gd T cells in Lyme arthritis, and Dr. Teuscher received a new R01 grant to examine genes associated with autoimmunity on the Y chromosome. Other accomplishments include Dr. Budd assuming the Chair of the NIH study section, "Immunity and Host Defense", effective July 1, 2007. As a result of all these combined efforts, the Vermont Center for Immunology and Infectious Diseases has been recognized as a center of excellence by the College of Medicine. This has been recognized by our new Dean, Dr. Frederick Morin. As part of a new faculty recruit initiative, all new faculty recruited to the College of Medicine are evaluated for their potential overlap with five areas of excellence, Cardiovascular, Lung, Cancer, Neuroscience, and Immunology/Microbiology. Thus, we have a remarkable long way since the inception of the Immunobiology Program 13 years ago with one founding member. Summary of continuing accomplishments during the current funding period -joint weekly laboratory meetings -seminar series of outside speakers -Offering of new courses in advanced immunology, grant writing skills, laboratory management skills, and transgenic mice -Initiation of a new graduate track in Immunology/Infectious Diseases -recruitment of the first of three new faculty in the areas of immunology and infectious diseases (Dr. Jason Botten) -Hosting of a 4-way joint COBRE meeting between UVM and Dartmouth -Submission of a center grant for an NIH-initiated vaccine trials by Dr. Kirkpatrick -Appointment of Dr. Budd as Chair of the Immunity and Host Defense NIH study section -Publication of several high profile manuscripts including one in Science Future Directions During the third year of funding, we will concentrate on : -recruitment of two additional new faculty -initiating the collaborations that formed as a result of our "challenge talks" -developing the new graduate student track in immunology