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Daniel Rotrosen, M.D., Director, DAIT
Dr. Rotrosen announced the following new staff members and scientific activities:
Ellen Goldmuntz, M.D., Ph.D. Dr. Goldmuntz joined the Division in July 2003 as a Medical Officer in the Clinical Immunology Branch. Dr. Goldmuntz received both her M.D. and her Ph.D. from the Albert Einstein College of Medicine of Yeshiva University, Bronx, NY. She completed her pediatric residency training at Children's National Medical Center and a fellowship in pediatric rheumatology in a combined program between Children's National Medical Center and NIAMS. Most recently, Dr. Goldmuntz has been a member of an academic pediatric rheumatology practice at Children's National Medical Center.
Crystal Y. Koh, Ph.D. Dr. Koh joined the Division in March 2003 as a Program Officer in the Transplantation Basic Sciences Section of the Transplantation Immunobiology Branch. Dr. Koh received her Ph.D. degree in immunology from the University of Texas Southwestern Medical Center at Dallas and was a CRTA fellow at National Cancer Institute at Frederick. Her research focus was improving the efficacy of bone marrow transplantation, promoting anti-tumor effects using immunotherapy, and dissecting the mechanism of NK cell recognition of normal vs. transformed hematopoietic cells in mouse models. She also served as an instructor for a graduate course, Ethics in Biomedical Sciences, at Hood College in Frederick, MD.
Patrice Holtz, R.N., M.B.A. Ms. Holtz joined the Division in May 2003 as Chief, Operations and Management in the Office of Clinical Applications. Ms. Holtz received her B.S. and M.B.A. degrees from Johns Hopkins University and also has an undergraduate degree in nursing. She has over 15 years experience in clinical research that includes positions at Covance, Inc., Johns Hopkins Medicine, and TRI, Inc., where she worked extensively in product development and clinical research with pharmaceutical and biotechnology companies.
Peter Gergen, M.D. M.P.H. Dr. Gergen joined the Division in February 2003 as a Medical Officer in the Asthma, Allergy, Inflammation Branch. Dr. Gergen received his M.D. from the University of Wisconsin-Madison and his M.P.H. from Columbia School of Public Health. He trained in Pediatrics at Montreal Children's Hospital and University of Washington, Seattle. Before joining the Division, Dr. Gergen was a Medical Officer at the Agency for Healthcare Research and Quality.
Sally Tinkle, Ph.D. Dr. Tinkle joined the Division in June 2003 as a Program Officer in the Asthma, Allergy and Inflammation Branch. Dr. Tinkle received her Ph.D. in physiology from the University of Colorado Health Sciences Center and was a postdoctoral fellow at the National Jewish Medical and Research Center, Denver, CO. Most recently, she was Team Leader of the Dermatotoxicology Laboratory at the National Institute for Occupational Safety and Health in the Centers for Disease Control and Prevention. Dr. Tinkle's research focused on the effect of work place stress on the development of skin allergy and the link between skin exposure and the development of pulmonary disease.
Francesca Macchiarini, Ph.D. Dr. Macchiarini joined the Division in May 2003 as a Program Officer in the Basic Immunology Branch. She received her M.S. in Molecular Biology from the University of Maryland in Baltimore County and her Ph.D. in Molecular Immunology from the University of Maryland School of Medicine. She completed postdoctoral work in both HIV and basic immunology research, and was a NIAID research fellow investigating the mechanisms of T cell development before joining the Division.
David B. Winter, Ph.D. Dr. Winter joined the Division in August 2003 as a Program Officer in the Basic Immunology Branch. He received his Ph.D. in microbiology and immunology at the State University of New York, Buffalo, and completed postdoctoral work on mutation of immunoglobulin genes at Johns Hopkins University and on DNA repair mechanisms at the National Institute of Aging in Baltimore. He worked as an independent investigator at the Walter Reed Army Institute of Research and the Uniformed Services University of Health Sciences before joining the Division.
Cynthia Reed. Ms. Reed joined the Division in May 2003 as a Program Specialist for the Immunoregulation Section of the Basic Immunology Branch. Before coming to DAIT, Ms. Reed was the Lead Grants Technical Assistant for the Scientific Review Program in DEA.
Kathryn D. Simon, Ph.D. Dr. Simon joined the Division in September 2003 as a Senior Regulatory Affairs Officer, in the Office of Clinical Applications. Dr. Simon received her Ph.D. in Biochemistry and Nutrition from Virginia Polytechnic Institute State University and completed her post-doctoral training at Northwestern University. She brings experience in pharmaceutical and medical device manufacturing; focus on quality assurance and regulatory affairs. Prior to joining the Division, Dr. Simon was the Technical and Regulatory Affairs Manager at Diosynth Inc (Des Plaines, Illinois), a subsidiary of Akzo Nobel.
Scientific Initiatives
NIAID Enhancement Awards for Underrepresented Minority Scientists- RFA: AI-03-045: The NIAID invites applications from underrepresented minority investigators who are in the early stages of their scientific careers (assistant professor or junior level faculty) to establish basic or clinical research programs in the areas of allergy, immunology, transplantation, microbiology, and infectious diseases, including AIDS.
Immune System Development and the Genesis of Asthma: RFA: AI-03-041: The NIAID and the National Heart, Lung, and Blood Institute (NHLBI) invite applications for research projects aimed at understanding early life changes in immune function that lead to the development of asthma. Identification of the cellular and molecular processes involved in the onset of asthma will provide the basis for devising novel and effective immune-based strategies for asthma treatment and prevention that do not compromise the integrity of the immune system and are not hampered by the limitations of current therapies.
Cooperative Centers for Translational Research on Human Immunology and Biodefense-RFA: AI-03-015: The NIAID invites applications from single institutions or consortia of institutions to increase the number of Cooperative Centers for Translational Research on Human Immunology and Biodefense originally established by NIAID in fiscal year 2003. The long-term goal of this program is the translation of research using animal models of immunity into clinical applications in humans. The immediate purpose is to support basic and translational research, and create the stable, flexible, centralized infrastructure needed to promote and coordinate multidisciplinary research in human immunology as it relates to defense against agents of bioterrorism and emerging/re-emerging infectious diseases.
Pathogenesis of Polyomavirus Associated Nephropathy- RFA: AI-03-019: The NIAID invites applications for basic, pre-clinical, clinical, and epidemiological research projects on polyomavirus associated nephropathy (PVAN), which is a serious, emerging complication in renal transplant recipients. Research in this area will enhance: understanding of latent polyomavirus reactivation and virulence in immunosuppressed individuals; knowledge of immune responses to polyomavirus infection associated with nephropathy; risk assessment; and preventive, diagnostic and treatment strategies for PVAN. This request for applications (RFA) will not support applications for clinical trials to investigate interventional strategies for PVAN.
Bench to Bedside Research on Type 1 Diabetes and its Complications-RFA: DK-03-019: This is a reissuance of RFA-DK-03-001. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), National Eye Institute (NEI), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Neurological Disorders and Stroke (NINDS), and the Office of Dietary Supplements (ODS) invite applications involving partnerships between clinical and basic biomedical researchers with the goal of translating advances in our understanding of the molecular basis of type 1 diabetes and its complications into new therapies for the prevention, treatment and cure of this disease. In these "bench to bedside" research partnerships, a team of clinical and basic scientists will conduct collaborative research that, if successful, will bring basic research advance from the laboratory to a point where a potential new therapy can be tested in patients or in preclinical studies in animal models.
Cooperative Research for the Development of Vaccines, Adjuvants, Therapeutics, Immunotherapeutics, and Diagnostics for Biodefense and SARS-RFA: AI-03-017: The NIAID invites investigator-directed cooperative research grant applications that will lead to the development of new vaccines, adjuvants, therapeutics, immunotherapeutics or diagnostics. These products should be focused on the toxins or pathogens listed in the NIAID Categories A, B and C list of priority pathogens (http://www.niaid.nih.gov/Biodefense/bandc_priority.htm), or their arthropod vectors.
Biodefense Research Training and Career Development Opportunities- NOT-AI-03-047: To expedite research training and career development in research areas focusing on biodefense, including prevention, detection, diagnosis, and treatment of diseases caused by potential bioterrorism agents.
Cooperative Clinical Trials in Organ and Tissue Transplantation-Public Comment- NOT-AI-03-048: The NIAID will be issuing a Request for Application (RFA) to support a clinical studies program on immune-mediated pathologic processes in organ transplantation. The purpose of this RFA will be to support a cooperative, multi-site consortium for clinical trials and/or observational studies to improve our understanding of and ultimately reduce the immune-mediated morbidity and mortality of organ transplantation. These studies will be carried out in pediatric and adult recipients of whole organ or tissue transplants.
DIVISION ACTIVITIES
Bronchoscopy and Bronchoprovocation in Clinical Research NIAID co-sponsored a workshop with NHLBI on July 25 and 26, 2003 to review the current state-of-science of bronchoscopy and bronchoprovocation as utilized in clinical research studies of asthma and other diseases of the airways. The workshop brought together clinical and basic scientists as well as experts in medical ethics and representatives from the FDA to discuss topics ranging from indications, safety and ethical considerations to the regulatory requirements pertaining to the administration of approved and unapproved agents in bronchoscopy and brochoprovocation clinical research protocols.
Expert Panel Meeting on Food Allergy In June 2003, NIAID convened an expert panel of internationally recognized scientists to evaluate the current state of food allergy research and to make recommendations for targeted basic science and clinical research which would support development of new, more effective interventions. Presentations included the natural history of food allergy, the cellular mechanisms of oral tolerance and food allergy, predictors of disease progression and disease severity, immunotherapeutics, and the causes and treatment of anaphylaxis. Expert panel discussions identified critical areas of research that, with dedicated funding, will provide significant advances in the prevention and treatment of food allergy. These areas included investigation of the acquisition and loss of oral tolerance, mucosal immunity, the immunopathology of anaphylaxis, characterization of food allergens, and the influence of route of exposure, adjuvant and genetic predisposition on development of allergy. The panel suggested that collaborative research programs might best support this goal.
The Alliance for Cellular Signaling Third Annual Meeting Pasadena, California; May 18-21, 2003 The Alliance for Cell Signaling Consortium (AfCS) is a large-scale collaborative program co-funded by NIGMS (lead), NIAID, NCI, several pharmaceutical companies, and private sources. The goal of the AfCS is to dissect G protein-coupled receptor signaling pathways in mammalian cells in order to understand how cells interpret and respond to external signals. All of the data, reagents, and information developed through the AfCS are freely available to the biomedical community worldwide through the AfCS Web site: http://www.signaling-gateway.org/ The AfCS made substantial progress during their third year of support. A significant amount of data has been generated on B cell ligand responses and is available on the Web site. In addition, the consortium generated an impressive number of useful reagents during the last two years (e.g., cDNA expression vectors, gateway-ready expression vectors, localization markers). These reagents, as well as information provided by the Alliance through the Web site (e.g., Molecule pages, Mini-Molecule pages, and an antibody efficacy and covalent modifications database will provide valuable knowledge to the signaling community.
Mathematical Models of Immunity Workshop: The NIAID convened an expert panel of immunologists and mathematical modelers on June 10-11, 2003 to advise on the state-of-the-art and the scientific needs for the development of mathematical models capable of simulating immune responses, directing novel experimentation, and generating a greater understanding of the immune system in infection, vaccination, and immune homeostasis. Participants provided overviews of several areas, including: analysis of immune-based signaling events; B cell maturation; maintenance of immunological memory; and pathogen/host interactions. They also introduced new methods for in silico analysis of cell signaling and behavior at various levels of resolution. The panel concluded that mathematical modeling has great potential to uncover immunological principles to drive the development of improved vaccines and immunotherapeutics against infectious agents and immune-mediated diseases, as well as to aid prediction of disease outcome, and of the safety and efficacy of candidate vaccines.
Expert panel discussions identified three critical areas that require support in order to advance the field. These areas include research infrastructure, education and training.
Antiviral Innate Immunity: Recognition, Defenses, Evasion, and Biodefense Strategies On June 24-25, 2003, the NIAID convened a meeting on innate immune responses to viruses, focusing on early host responses to viral infection and the impact of innate immune responses on the viral infectious process and subsequent adaptive immunity. The goals of this meeting were to provide a comprehensive overview of the area, identify gaps in the research and identify practical applications for biodefense and emerging viral infections. Presentations included innate cytokine and chemokine responses, viral recognition and innate immune activation, viral immune evasion, and insights from innate immunity into better methods for developing vaccines and therapeutics for viral infections. This meeting proved highly valuable as an update on a rapidly moving field and for identifying possible NIAID research opportunities on antiviral innate immunity.
Genomics of Transplantation Workshop On April 30 - May 1, 2003 NIAID convened an Expert Panel of approximately 20 scientists to address the state-of-the-science in complex trait disease and transplantation genomics; identify gaps in knowledge; and advise NIAID on immediate and long-term scientific opportunities in transplantation genomics to fill these gaps. The Panel consisted of a multi-disciplinary group of transplantation, genomics, and pharmacogenomics researchers, in addition to genetic epidemiologists, biostatisticians, and bioinformatics experts. The workshop featured the following sessions: (1) progress and challenges in clinical organ, tissue, and cell transplantation genomics; (2) genetic basis for disease susceptibility and outcome; (3) transplantation genomics and expression profiles; (4) pharmacogenomics; and (5) biostatistical tools and bioinformatics. A panel discussion provided key recommendations for future collaborative efforts to apply genomics research to critical issues of organ, tissue, and/or cell transplantation.
American Transplant Congress (ATC) 2003 Annual Meeting: ATC is the joint, annual meeting of the American Society of Transplantation and the American Society of Transplant Surgeons, and was held in Washington, D.C. on May 31-June 4, 2003. June 3, Dr. Anthony Fauci delivered the keynote address "NIAID Transplantation Research: Progress and Priorities." In his address, Dr. Fauci confirmed NIAID's long-standing support for transplantation immunology research, described the breadth of NIAID's basic, pre-clinical, and clinical research programs, and outlined new directions for NIAID-supported research in transplantation. On June 3, NIAID co-sponsored the symposium "CD8 T Cell Biology" The program included presentations by leading investigators on T cell activation, expansion, and memory.
International Society for Heart and Lung Transplantation 23rd Annual Meeting The International Society for Heart and Lung Transplantation held its 23rd annual meeting in Vienna, Austria on April 9-12, 2003. NIAID co-sponsored several symposia and plenary lectures on clinical trials in immune tolerance induction to allogeneic organs and methods for monitoring immunity and tolerance in transplant recipients.
Humoral Rejection in Solid Organ Transplantation: On April 23-24, 2003 NIAID and the NIH Office of Rare Diseases co-sponsored this conference in Bethesda, MD to examine the role of humoral rejection in solid organ transplantation. The objectives of this conference were to formulate diagnostic criteria, assess the relevance of immune profiling, develop potential immunologic paradigms, and assess the effectiveness of current treatment protocols for humoral rejection. Objectives for future clinical trials to assess the effectiveness of intervention strategies were outlined. Recommended areas of research include assessing the relationship between sub-clinical diagnosis and chronic changes in the allograft, the effectiveness of desensitization procedures in preventing progression of injury, and the role of complement and non-HLA antibody in allograft dysfunction. Additional meeting co-sponsors were The American Society of Transplantation, American Society of Transplant Surgeons, National Kidney Foundation, International Society of Heart and Lung Transplantation, American Society of Histocompatibility and Immunogenetics, Division of Transplantation of the Health Research Services Administration.
REPORT FROM THE EXPERT PANEL ON FOOD ALLERY
Ad hoc Council member Dr. Hugh Sampson, Mount Sinai, School of Medicine and moderator, and discussant Marshall Plaut, M.D., Section Chief, Asthma, Allergy and Inflammation Branch opened the discussion with a presentation on The Expert Panel on Food Allergy. General overview of the topics was presented: nature and the scope of the problem from basic immunology-related to oral tolerance development, the role of mucosal immunity, food allergic reactions that induce anaphylaxis, new prediction methodologies, issues related to the sensitization properties of different food allergens, mechanisms related to loss of sensitization and protection from it and animal models and therapeutic approaches.
PROGRESS REPORT ON MULTIPLE AUTOIMMUNE DISEASES GENETICS CONSORTIUM
Dr. David Johnson, Program Officer, Clinical Immunology Branch presented a general overview of the on-going progress of this consortium.
CONCEPT REVIEW
All concepts were presented and approved.
Food Allergy Research Consortium: This initiative will support basic, pre-clinical and clinical research on food allergy, in order to provide critical information concerning the pathophysiology and natural history of food allergy, including life-threatening food allergy, and develop effective interventions for this disease. These studies will: evaluate the molecular and functional characteristics of food allergens, including food allergens associated with life-threatening anaphylaxis; evaluate the unique properties of the gastrointestinal tract that promote natural tolerance and the failure of tolerance that underlies food allergy; develop animal studies to characterize inbred strains and humanized mice, and of non-human primates, for their suitability as models of food allergy; establish a repository of patient samples and associated information to study the natural history of food allergy, including the mechanisms underlying both the redevelopment of tolerance following sensitization to food allergens and the acquisition of new food sensitivities; develop new immunologic approaches to prevent and/or treat food allergy; develop novel educational programs for patients and their families; and establish a statistical and data coordinating center.
Immunobiology of Acute Asthma: Investigations will focus on: (1) the clinical, cellular and molecular characterization of acute asthma exacerbations in humans; (2) identification of biomarkers useful in predicting the susceptibility to acute asthma attacks; (3) mechanisms of lung damage induced by aeroallergens associated with acute asthma in humans; (4) role of innate and adaptive immune mechanisms in initiating or modulating acute asthma episodes; (5) identification of molecular triggers and mediators of acute asthma exacerbations in humans; (6) immune tolerogenic approaches to reducing the severity and frequency of acute asthma exacerbations.
Modeling Immunity to Emerging/Re-emerging Infectious Diseases: This program will support multi-disciplinary Centers focused on developing a mathematical modeling package that provides tools for high (whole organism or system), intermediate (tissue or organ), or fine (single cell) resolution modeling of host immune responses to infection and vaccines, with an emphasis on NIAID Category A-C pathogens.
The research team will consist of immunologists, physicists, mathematicians, computer scientists, and infectious disease experts. Centers may be "virtual;" however, frequent interactions and communication are key elements to the program's success. Investigators may choose to focus on various aspects of innate or adaptive immunity, as well as the interface between innate and adaptive immune responses. Each Center will have strong bioinformatics and training components: (i) the bioinformatics component will develop methods to foster data sharing and communication among the Centers, and facilitate the development and distribution of "user-friendly" immune modeling tools to the broader research community; and (ii) the training component is directed at graduate students and post-doctoral fellows, and senior scientists working in the fields of immunology, mathematics, physics, and engineering, and: (a) will develop programs that provide trainees with an understanding of the power of applying mathematical principles to biological phenomena in immunology; drawing from other fields, such as population genetics, ecology, and epidemiology; and (b) may develop teaching tools based on simulations of immune function.
Disabling Innate Immune Evasion: Rational Attenuated Vaccines: To establish the molecular mechanisms of innate immune evasion by viruses and bacteria and use this knowledge to create novel attenuated strains for vaccines. Because pathogens possess specific genes that function to overcome critical innate immune defenses, pinpointing and deleting those genes promises to generate organisms that cannot infect, but can stimulate innate and adaptive immune responses. This approach will require using current, emerging, and new information about innate host defenses and pathogen evasion molecules to design attenuated strains. The development of novel attenuated strains that are potentially safer than current strains, and whose underlying basis of attenuation is well understood will be valuable for the development of vaccines and therapies for biodefense and emerging diseases.
Immune Function and Biodefense in Children, Elderly, and Immuno-Compromised: Research contracts will be supported to identify, analyze, and modify specific immune parameters that prevent effective and/or safe vaccination or immunotherapy in one or more of these special populations, in the context of protection against one or more of the NIAID Category A, B, or C pathogens of bioterrorism and emerging/re-emerging diseases. Research will focus on: describing expression patterns, densities, and signaling capabilities of innate and adaptive immune receptors, ligands, and cell types that differ in between a special population and normal healthy adults; analyzing immune response kinetics and immunoregulation patterns that contribute to differential control of infection or response to vaccination; and developing new methods to induce more effective immune responses, such as phagocytosis, antimicrobial peptide production, T and NK cell- mediated cytotoxicity, antibody production, and long term T and B cell memory. Animal studies will be allowed only if they are directly relevant to the human situation and model or verify clinically important aspects of immunity.
Imaging Technologies for Immunity to Infectious Diseases: This program will support the in vivo study of immune responses to category A-C pathogens and emerging/reemerging infectious diseases by: 1) applying imaging technologies to the study of immune function; 2) characterizing immune cell function in vivo, which may lead to the development of novel immune therapies for infectious diseases; and 3) fostering interdisciplinary studies that stimulate development of novel solutions to biological questions using a broader range of technologies. Requiring the applicants to develop collaborations with NCI- and NCRR-supported Imaging Centers and Small Animal Imaging Resources Programs will facilitate achievement of these goals.
Large Scale Antibody and T Cell Epitope Discovery Program: This program will consist of: 1) identification of linear and conformational antibody epitopes; 2) identification of immunodominant and subdominant T cell epitopes that bind class I, class II and non-classical MHC molecules; 3) definition of peptide binding motifs on a sufficient number of HLA alleles to cover the human population worldwide; and 4) design and development of novel or improved high throughput screening assays for antibody and/or T cell epitope discovery that are easily transferable to the broader scientific community, thus providing standardized methods to facilitate more rapid discovery.
Population Genetic Analysis Program: Immunity to Vaccines/Infections: This program will solicit new contracts to study the association of genetic polymorphisms with host immune responsiveness to infections and vaccination, particularly category A-C pathogens and those implicated in emerging/re-emerging infectious diseases. New studies will be initiated on the functional aspects of polymorphisms in immune response genes, the identification of the immune mechanisms of host susceptibility or resistance to an infection, and on the immune factors that play a critical role in controlling, protecting, or predisposing to an infection or that might serve as targets for passive immunotherapy. Genomic information and mouse models will facilitate identification of the molecules and mechanisms of action involved in the immune response to a pathogen. The information gained from animal studies will be used to identify parallel mechanisms in humans. Materials for these studies will be obtained from patients with a history of natural infection, individuals enrolled in vaccine trials, and high-risk groups (e.g., military, laboratory, and health care personnel; very young, elderly; or immune deficient individuals). Interdisciplinary teams that combine diverse scientific expertise (e.g., microbiology, immunology, genetics, mathematics, computer science) will be encouraged.
Hyperaccelerated Award/Mechanisms in Immunomodulation Trials: Expansion to Include Biodefense The renewal of this program will incorporate the same elements pioneered by NIAID in FY 1999 to facilitate submission, peer review, and award of successful applications within 13 weeks of receipt for highly meritorious applications, including: 1) monthly receipt of applications; 2) monthly internet- and teleconference-based peer review; 3) negotiated assignments among participating ICs; and 4) expedited council approval. This renewal will also incorporate all aspects of RFA AI-02-003, released March 2002, in addition to NOT-AI-02-034 (released July 2002), to expand funds available to mechanistic immunological studies in clinical trials of vaccine candidates for Category A-C agents. Studies focus on the inclusion of patients and utilization of patient samples for: evaluation of immunologic and other relevant parameters to facilitate the study and definition of immunological mechanisms underlying the intervention; definition and characterization of the mechanisms of disease pathogenesis; definition of surrogate/biomarkers of disease stage, activity, and therapeutic effect; definition and characterization of the human immune system; and evaluation of the underlying immune mechanisms of effective responses to candidate vaccines. Proposed mechanistic studies associated with clinical trials supported by industry are particularly encouraged. back to top |