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Research Opportunities for Pediatric Allergy and Immunology Fellows

Robert Wood, M.D., is currently professor of Pediatrics in the School of Medicine and of International Health in the Bloomberg School of Public Health. Dr. Wood’s research program initially focused on the relationship of indoor allergens to asthma and allergic rhinitis. However, while these studies are still underway, over the past 10 years, he has also expanded his focus to include numerous studies on childhood food allergy, which is now a major focus of his research. He is extremely well funded, with the bulk of his funding balanced between pediatric asthma and food allergy, and the remainder coming from a wide array of collaborative projects.

His main, current projects are as follows:

1) Consortium of Food Allergy Research (CoFAR): In 2005 Dr. Wood received an NIH Grant that allowed for the formation of the Food Allergy Research Consortium. This was the first NIH funding dedicated to food allergy, which came as a response to the rapid rise in food allergy that has occurred in recent years. Five sites were chosen to form the Consortium — Mt. Sinai, Duke, National Jewish, Arkansas Children’s Hospital and Johns Hopkins. The Consortium was charged with conducting both epidemiologic studies on food allergy and interventional studies directed at developing treatments for food allergy. Four protocols are currently underway, including a) an observational study of infants presenting with food allergy who will be followed prospectively, seeking to determine the clinical and laboratory factors that predict their long-term outcome; b) a study of oral egg immunotherapy in children with persistent egg allergy; c) a study of sublingual peanut immunotherapy for adolescents and adults with persistent peanut allergy; and d) a Phase 1 study, the first recombinant peanut vaccine ever used in a human trial. Most important, CoFAR recently received a second five years of funding, with Johns Hopkins continuing as one of the five clinical sites under Dr. Wood’s leadership.

2) Immunotherapy for persistent food allergy: In 2006 Dr. Wood and Justin Skripak, then a second-year fellow, initiated the world’s first double-blind placebo-controlled study of oral immunotherapy for children with severe, persistent milk allergy. This study demonstrated a dramatic response to therapy and resulted in two publications in the Journal of Allergy and Clinical Immunology. Subsequently, in addition to the CoFAR studies noted above, Dr. Wood and Dr. Keet initiated a second milk immunotherapy study comparing oral and sublingual administration of milk protein, the results of which in press in the Journal of Allergy and Clinical Immunology, as well as a study examining the combination of omalizumab and milk immunotherapy, and a study comparing oral and sublingual immunotherapy for peanut allergy.

3) The Inner City Asthma Consortium (ICAC): Dr. Wood is the principal investigator for the ICAC site at Johns Hopkins. The consortium includes several protocols, including novel treatment approaches for inner-city asthma and a birth cohort study to follow children from the inner city at risk for the development of asthma. Dr. Wood has had primary responsibility for the birth cohort study (URECA) that began in 2005, an exciting project that has now been funded to continue through 2015. More recently, Dr. Wood has served as the Consortium PI for a study to assess the safety of sublingual cockroach immunotherapy, the first study in the world to address this potential treatment for inner-city asthma. An additional multicenter cockroach immunotherapy study that will assess a number of immunologic biomarkers is now being developed, for which Dr. Wood is also serving as Consortium PI, with the goal being a larger efficacy trial in the next phase of ICAC funding which was recently granted by the NIH.

4) Asthma and Allergic Diseases Research Center (AADRC): In 2006 Johns Hopkins was awarded an AADRC grant for a series of proposed studies on the immunobiology of IgE, entitled the “Efficacy of IgE in Mediating Allergic Reactions in Vivo.” With Dr. Donald MacGlashan serving as PI, this grant includes a series of studies that will use omalizumab to modify IgE and thereby study the role IgE is playing in a variety of allergic responses, including nasal allergen challenge, natural cat allergen challenge and food challenge in food allergic subjects. Dr. Wood serves as the PI of the human subject core and is in charge of the food challenge protocol that he is conducting with a second-year fellow from the adult Allergy and Immunology Fellowship Program.

5) Studies on cat-induced asthma and allergic rhinitis and the potential for pharmacologic intervention: In 1990 Dr. Wood created an environmental challenge system for the study of allergic responses to airborne cat allergen. This model has allowed for extensive study of allergic responses in both the upper and lower airways to naturally generated cat allergen. The effects of varying allergen level, particle size distribution, individual patient sensitivity and airway reactivity on these responses have been studied in detail. In addition, the challenge system has been used to study the effects of various pharmacologic interventions on both nasal and asthmatic responses to cat exposure. These studies have included nasal steroids, immunotherapy and the leukotriene antagonists, zafirlukast and montelukast. In addition to specifically defining the effects of treatment on asthma and allergic rhinitis due to cat allergen, these studies have also proven especially useful in defining relationships between upper and lower airway responses because the challenge provides simultaneous exposure to the entire respiratory tract. Most recently, Dr. Wood has been studying the effects of omalizumab, a humanized anti-IgE antibody, on cat room responses, which will serve as a prelude to the AADRC cat studies noted above.

6) Studies on the natural history of food allergy: Utilizing his large pediatric allergy clinic, where he follows over 4,000 children with food allergy, Dr. Wood has published a series of studies on the natural history of food allergy. Beginning in 1998, Dr. Wood initiated a study on the natural history of peanut allergy. The initial study resulted in an important publication in which it was reported that over 20% of children with peanut allergy outgrow their allergy over time. A second paper on peanut allergy was published that further defined the appropriate parameters for performing an oral peanut challenge in children with a history of peanut allergy, and a third paper was published describing the potential for a recurrence of peanut allergy in some children who had previously outgrown their allergy. Beginning in 2003, a similar study was conducted in patients with tree nut allergy. Over the last five years, Dr. Wood has completed and published five additional studies on the natural history of milk, egg, soy and wheat allergy in children and peanut allergy in adults. Of note, these important studies have all yielded first-author publications for fellows in training, as have numerous other papers utilizing this extraordinary clinical base.

7) Allergic reactions to childhood immunizations: In collaboration with Dr. Neal Halsey from the School of Public Health and with funding from the CDC, Dr. Wood is conducting a series of studies on allergic reactions to childhood immunizations. As part of a larger project to study adverse reactions to immunizations, these studies will be the first to comprehensively evaluate large cohorts of children who have experienced possible allergic reactions to immunizations. Two manuscripts, including a comprehensive approach to the management of patients who have experienced possible allergic reactions, have now been published from this collaboration.

Howard Lederman, M.D., Ph.D., is a professor of Pediatrics and Internal Medicine and the director of the Immunodeficiency Clinic, the Pediatric Immunology Laboratory and the Ataxia-Telangiectasia (A-T) Clinical Center. Dr. Lederman’s laboratory is concerned with the functional activities of T and B-lymphocytes, particularly as they relate to infectious and allergic diseases.

His current projects include:

1) Biology of Ataxia-Telangiectasia: Dr. Lederman is the director of the Ataxia-Telangiectasia Clinical Center at Johns Hopkins. This is a multidisciplinary clinic, funded by a private foundation (A-T Children’s Project) to provide clinical service and conduct clinical research on patients with this very rare primary immunodeficiency disorder. The clinic has already seen more than 250 A-T patients and annually sees approximately 30 new patients from all parts of the world. More than two dozen faculty members are involved in A-T related projects such as defining the natural history of this disease, developing a neurologic scoring scale, understanding the reasons that some patients develop chronic lung disease and/or lymphoma, and understanding the pathophysiology of the neurodegenerative disease. Studies of immune function are aimed at understanding the etiology of IgA deficiency that occurs in almost two-thirds of A-T patients. Dr. Lederman is testing hypotheses that (a) IgA deficiency is due to an abnormality of TH2 helper function and (b) that IgA deficiency is due to the inefficiency of the B lymphocyte to repair double-strand DNA breaks after switch recombination. He is using lymphocytes to develop more rapid and sensitive diagnostic tests for A-T, based upon quantitative analysis of the ATM protein and its biological activity to phosphorylate p53. Finally, he is collaborating with the Department of Genetics to develop techniques for investigating the seven effects of polymorphisms in 30-40 genes on the expression of the A-T phenotype, particularly as it relates to immune function such as IgA deficiency.

2) Role of T cells in environmental allergies: Dr. Lederman’s laboratory is also one of four core laboratories to perform T lymphocyte functional analyses in the URECA birth cohort study component of the NIAID sponsored National Cooperative Inner City Asthma Consortium. This multicenter prospective trial (clinical collaborators in Baltimore are Drs. Robert Wood, Peyton Eggleston and Elizabeth Matsui) is designed to intensively follow a birth cohort of children for at least seven years for the development of environmental respiratory allergies and asthma. A comprehensive panel of immunologic tests, as well as close monitoring of the environment and respiratory tract infections, will be performed to allow retrospective analysis of the factors most important to the development of respiratory allergies and asthma. Dr. Lederman's laboratory will perform measurements of T lymphocyte function, including assessing proliferation and cytokine expression after stimulation with a variety of antigens and mitogens, and assessing the T cell phenotype by assessment of cell surface proteins.

3) Pathophysiology of Primary Immunodeficiency Diseases: As the director of the Immunodeficiency Clinic and the Pediatric Immunology Laboratory at Johns Hopkins Hospital, Dr. Lederman is involved in the clinical care and laboratory evaluation of a wide range of patients with defects in immune function. Dr. Lederman and various collaborators have used patients in his clinic to identify the genes responsible for two new primary immunodeficiency diseases: (a) BLNK deficiency — an autosomal recessive disorder of B cell differentiation that give the phenotype of congenital agammaglobulinemia, and (b) X-linked autoimmunity allergic dysregulation (XLAAD) or Immunodeficiency polyendocrinopathy enteropathy X-linked (IPEX) — a disorder of a cytokine gene binding protein whose malfunction leads to uncontrolled activation of T lymphocytes, particularly those with a TH2 phenotype. He has also been instrumental in developing a new type of immunomodulatory therapy (high-dose cyclophosphamide) for chronic enteropathy in children. Such patients provide a wealth of material for clinical and laboratory research projects.

Elizabeth Matsui, M.D., is currently an associate professor of both Pediatrics and Epidemiology and Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health. Dr. Matsui joined the faculty in 2003 after completing her fellowship in our division with the support of this training grant. She has enjoyed tremendous success and has quickly developed a well-funded and very independent research program. She was promoted to the rank of associate professor in just her fifth year on the faculty and now holds multiple NIH grants, including an UO1 and an RO1, for her studies on pediatric asthma and the role of environmental allergen exposure on disease activity and immunologic responses. She is rapidly rising in national prominence for her work, was recently named to the editorial board of the Journal of Allergy and Clinical Immunology, and is now regarded as one of the outstanding mentors in our program. She also completed her master’s in Epidemiology as a fellow and first-year faculty member, and with this background brings an added dimension to her research as well as to her education of the trainees.

Her current projects include:

1) Occupational Mouse Allergy: Exposure and Allergen-specific Immune Responses: Data from Dr. Matsui’s prospective cohort study of laboratory animal workers have indicated that the risk of mouse-specific IgG increases with increasing exposure to the major mouse allergen, Mus m 1. In contrast, the risk of IgE sensitization to mouse peaks at moderate levels of exposure and decreases at high levels of exposure. Ongoing data analysis is being conducted to determine the effect of atopy and concomitant endotoxin exposure on these dose-response relationships and to correlate mouse-specific antibody responses to allergic symptoms. Dr. Matsui has launched a follow-up of the first longitudinal cohort study of mouse workers to determine if mouse-specific antibody responses could serve as a biomarker of risk of developing allergy and to examine relationships between exposure and the development of cellular immune responses.

2) Mouse Allergen and Inner-city Asthma: Dr. Matsui and others had previously shown that mouse allergen exposure is a major cause of asthma morbidity in inner-city children with asthma. The primary aim of the Mouse Allergen and Asthma Intervention Trial (MAAIT) is to examine the efficacy of an environmental intervention aimed at reducing home mouse allergen levels. To accomplish this aim, 350 mouse-sensitized asthmatic children in Boston and Baltimore are randomized to receive either education about integrated pest management or integrated pest management delivered by professional pest management companies and trained research staff. The children will be followed for one year with repeated assessment of settled dust and airborne mouse allergen exposure and health outcomes. In addition, she is evaluating subcutaneous immunotherapy with mouse allergen extract in a phase I/II study of mouse-sensitized adults with asthma. To assess the clinical efficacy of mouse immunotherapy, she has established a mouse allergen environmental challenge chamber to assess upper and lower airways responses to mouse allergen exposure.

3) Allergen-Pollutant Interactions in a Nasal Challenge Model: Dr. Matsui is also studying the effects of indoor particulate matter (PM) on the upper airway, and whether indoor PM potentiates responses to allergen exposure in sensitized asthmatics. This project is a part of the Center for Childhood Asthma in the Urban Environment, a program project funded by the NIEHS and EPA. To this end, Dr. Matsui has collected bulk PM from inner-city homes and established methods to prepare the PM for nasal challenge studies. Nasal challenges are ongoing and data suggest that this will be an important model for understanding mechanisms of, and evaluating treatments for, pollutant induced airways inflammation. Dr. Matsui is also a co-investigator on another project from the center, a panel study of mouse-sensitized children that has been designed to test the hypothesis that pollutants and allergens interact, potentiating the clinical effects of the other.

4) Dietary Interventions in Asthma Treatment: Dr. Matsui directs projects evaluating the role of diet and dietary factors in asthma. These studies are a part of the Center for Childhood Asthma in the Urban Environment funded by the NIEHS and EPA. In the first study, Dr. Matsui is studying the effects of broccoli sprouts, which are a rich source of a potent antioxidant, sulforaphane, on asthma. Adults with mouse allergen induced asthma are randomized to broccoli sprouts or a placebo sprout and inflammation, oxidative stress, and upper and lower airway responses to mouse allergen are evaluated. In the second study, adults with asthma will be randomized to their usual diet or to a Mediterranean-like diet and inflammation, oxidative stress, and upper and lower airway responses to mouse allergen will be evaluated.

5) Studies on Inner-City Asthma: In collaboration with Drs. Wood and Lederman, Dr. Matsui is a co-investigator in the Inner City Asthma Consortium (ICAC). She recently chaired the writing group for one of the main outcome papers of the ICAC studies, a study on the relationship of allergy and allergen exposure in as study of children and adolescents with moderate to severe asthma. She also serves as the PI for an ICAC study by evaluating the role of microbial exposures in the development of asthma.

6) Dr. Matsui also has established a number of long-standing collaborations with investigators with a range of expertise. The range of disciplines represented by her collaborators includes biostatistics, environmental health sciences, immunology, animal models and pulmonology. Dr. Matsui also directs a Data Management and Analysis Core that consists of data analysts, data managers and programmers. These collaborations and resources, in addition to serving key roles in Dr. Matsui’s research program, also serve as a rich resource for fellows who interact with these collaborators during their research training with Dr. Matsui.

Pamela Guerrerio, M.D. Ph.D., is currently an assistant professor of Pediatrics. Dr. Guerrerio completed the M.D./Ph.D. Program at Johns Hopkins and did her graduate work in the Human Genetics Program under the mentorship of Dr. Hal Dietz. She stayed at Johns Hopkins to complete her clinical training including a fellowship in Pediatric Allergy and Immunology in our division. She joined our faculty in 2009. Her research interests focus on the genetic and immunologic mechanisms underlying food allergy and the loss of mucosal tolerance.

Her current projects include:

1) Investigation of the Role of TGF in Allergic Disease: As a fellow and now as faculty, Dr. Guerrerio has been investigating the immunologic defects associated with a new autosomal dominant aneurysm syndrome, called Loeys-Dietz syndrome (LDS), which is caused by mutations in the receptors for TGF. She has found that these patients have a striking predisposition to develop allergic disease, including food allergy, asthma, eczema and eosinophilic esophagitis. This is the first Mendelian disorder to be specifically associated with the development of allergic disease, and it provides an exciting and unique opportunity to study the importance of TGF in the pathogenesis of these disorders. Using both patient samples and a mouse model of LDS, current efforts are focused on understanding the biochemical and cellular changes caused by LDS mutations and how this information can be utilized to develop novel therapeutic strategies.

2) Immunologic Mechanisms Underlying Oral Tolerance: In collaboration with Dr. John Schroeder, Dr. Guerrerio has had the unique opportunity to study the immunologic mechanisms underlying the development of desensitization and/or oral tolerance in children undergoing immunotherapy for food allergy. These studies have focused on the role of basophils, dendritic cell and T cells in both innate and adaptive immune responses. Future studies will address the role of antibodies, including IgG, in modulating the behavior of these cell types.

3) Mechanism of Spontaneous Basophil Histamine Release: Basophils from up to 80% of children with food allergy spontaneously release histamine in the absence of allergen exposure. Although this phenomenon was first recognized decades ago, the underlying mechanism is unknown. In collaboration with Dr. Schroeder, Dr. Guerrerio has been investigating the signaling pathways and other determinants of this unique basophil phenotype.

Corinne Keet, M.D., M.S., is currently an assistant professor of Pediatrics. Dr. Keet joined the faculty after completing her fellowship in our division. She does clinical and translational research on food allergy. As a fellow, with the mentorship of Dr. Robert Wood, she had two significant projects that focused on different aspects of food allergy. The first used the large patient population of the division to evaluate the natural history of wheat allergy. The second, ongoing project is a clinical trial comparing sublingual and oral immunotherapy for treatment of milk allergy in children. As a faculty member, she continues to focus on the epidemiology and treatment of food allergy. Currently she is pursuing a Ph.D. in Clinical Epidemiology as a KL2 Clinical Research Scholar funded by the NIH.

Her current projects include:

1) Immunotherapy for Food Allergy: Immunotherapy for food allergy has emerged as a promising therapy for food allergy in recent years, but it is not yet ready for clinical use. As a fellow, Dr. Keet started a clinical trial comparing sublingual and oral immunotherapy for treatment of food allergy in children. This study is ongoing and addresses some of the fundamental questions outstanding in this area, including which method of administration is superior, whether the clinical effects represent desensitization or true tolerance, and what the immunologic mechanisms are for the observed clinical effects. The latter question is addressed through a productive collaboration with Pam Guerrerio, M.D., Ph.D., and John Schroeder, Ph.D. Preliminary results are in press at JACI. Based on Dr. Keet’s preliminary results in the study of milk immunotherapy, in her second year of fellowship she initiated a new collaboration with faculty in Biomedical Engineering at Johns Hopkins and the School of Pharmacy at University of Maryland to improve on sublingual immunotherapy delivery. In her third year of fellowship, she and her mentor, Dr. Wood, successfully competed for a grant from Johns Hopkins Institute for Clinical and Translational Research (ICTR) to pursue this project. This clinical trial, which will be of a novel method of sublingual immunotherapy for treatment of peanut allergy, started in 2011.

2) Epidemiology of Food Allergy: Many aspects of the epidemiology of food allergy remain unclear, including what environmental and genetic factors increase the risk for food allergy. Ultimately, Dr. Keet is interested in how genetic factors interact with the environment to affect oral tolerance. To that end, she is currently analyzing data on patients seen in the pediatric allergy clinic and data from NHANES, which is a large national survey of U.S. residents, in order to clarify geographic and seasonal risk factors for food allergy and other atopic diseases. During her Ph.D. in Clinical Epidemiology, she will focus further on identifying genetic and environmental risk factors for food allergy, starting by characterizing the food allergic phenotype. To do this, she will utilize the outstanding resources available through the Johns Hopkins School of Public Health.

3) Improving Food Allergy Diagnostics: Diagnosis of IgE mediated food allergy has always relied on clinical history, confirmation of food specific IgE by skin testing or quantifying serum IgE, and food challenge. For IgE mediated food allergy, each step of this diagnostic pathway has limitations, as specificity of clinical history and food specific IgE remains low, while food challenge is cumbersome. For food allergy that is not primarily IgE mediated, the current diagnostic methods are even poorer; for EE caused by food allergy, there is no clear method of determining the causative food allergen. Dr. Keet has two projects that address these questions. The first uses the incredible clinical resources of the division to clarify the utility of peanut IgE component analyses for determining when to do a food challenge. The second, which has just started and is a collaboration with Dr. Matsui and Dr. Wood, looks at local markers of the allergic response in children with IgE mediated and non-IgE mediated allergy.

Participating Faculty from Outside Our Division:

N. Franklin Adkinson, M.D., is currently professor of medicine and co-director of the combined fellowship in Adult and Pediatric Allergy and Immunology. As the longtime training program director, Dr. Adkinson has been actively involved with our pediatric fellows and faculty in teaching, clinical activities, and research mentoring and collaboration. His research has focused on drug allergy, latex allergy, immunotherapy and, more recently, long-term outcomes of childhood asthma. He is also director of the Graduate Training Program in Clinical Investigation, which is a tremendous resource to fellow trainees from all disciplines at Johns Hopkins.

Kathleen Barnes, Ph.D., is currently Professor of Medicine in the Division of Allergy and Clinical Immunology. She has long-standing research interests in immunogenetics of allergic responses and genetic epidemiology of acute and chronic obstructive pulmonary disease. More recently, she has entered active collaboration with Dr. Wood on the genetics of food allergy and is also a co-investigator with Drs. Wood and Halsey in a study of immunogenetics in the pathogenesis of vaccine hypersensitivity, and with Drs. Matsui and Diette in the Center for Childhood Asthma in the Urban Environment.

Bruce Bochner, M.D., is currently professor of Medicine and division director of Allergy and Clinical Immunology of the Department of Medicine. He has been an associate editor for the Journal of Allergy and Clinical Immunology since 1993, is the associate editor for Clinical and Translational Medicine, and is an editor of the Middleton’s Allergy: Principles and Practice textbook. He is on the board of directors of the American Academy of Allergy Asthma and Immunology. His research interests include the mechanisms of allergic diseases and pathways regulating eosinophil, basophil and mast cell recruitment, activation and survival during allergic inflammatory responses. Over the years, his work has focused on the role of cytokines (e.g., tumor necrosis factor, interleukins 4, 5 and 13), chemokines (e.g., eotaxins, MDC and TARC) and adhesion molecules (e.g., VLA-4, VCAM-1 and ICAM-1) in these events. Most recently, his lab has studied the function, expression and genetics of Siglecs on human eosinophils, basophils and mast cells, especially Siglec-8 and Siglec-F. He is a collaborator with Dr. Wood on the NIAID Asthma and Allergic Diseases Research Center Grant and, although he has not directly mentored any recent pediatric fellows, he has been instrumental in forging relationships with the pediatric allergy division and coordinating the activities of our fellows within laboratories in his division.

Patrick Breysse, Ph.D., is currently the director of the Division of Environmental Health Engineering and is the director of the Occupational and Environmental Hygiene Academic Program in the Johns Hopkins Bloomberg School of Public Health. He is also the director of the Center for Childhood Asthma in the Urban Environment, a role that he assumed when Dr. Eggleston retired from our division, and on which Drs. Matsui, Barnes, Diette and Hansel are co-investigators. His research focuses on the evaluation and control of chemical, biological and physical exposures that can affect health or well-being. Dr. Breysse's research currently includes studies of indoor and outdoor air pollution and childhood asthma. He is also researching secondhand smoke exposure assessment methods using airborne and hair nicotine. He has an outstanding record of training both pre- and postdoctoral students and co-mentored Dr. Matsui in both her fellowship research as well as in her K23 grant.

Gregory Diette, MD, M.P.H., is an Associate Professor of Medicine in the Division of Pulmonary and Critical Care Medicine and of Epidemiology in the Johns Hopkins Bloomberg School of Public Health. His directs a large and well-funded clinical research team and is the Director of Research for the Pulmonary Division. His research focuses on asthma epidemiology and the genetic and environmental determinants of asthma severity and morbidity. He has been very instrumental to our training program over the past 8 years, when he first began collaborating with Dr. Eggleston. He co-mentored Dr. Matsui (with Dr. Eggleston) during her fellowship and K23 award and subsequently co-mentored another fellow, Dr. Hemant Sharma (with Dr. Matsui) during his fellowship, as well as for his master’s in Epidemiology thesis. Harold Dietz, M.D., is currently the Victor A. McKusick Professor of the Institute of Genetic Medicine and Professor of Pediatrics, as well as a Howard Hughes Investigator. His laboratory has focused on the development and homeostasis of the arterial wall. He initially studied Marfan syndrome with widely acclaimed breakthroughs in the understanding of the genetics, pathophysiology, and treatment of this disease. A second major interest of his laboratory is to understand the mechanism of nonsense-mediated mRNA decay, to evaluate its basic biologic purpose, and to assess its role as a potent modulator of disease severity in a wide variety of genetic disorders. This was in fact the focus of Dr. Guerrerio’s work, who is now a third year fellow in our division, when she did her Ph.D. in Dr. Dietz’s laboratory. More recently, he has focused his attention on a newly discovered genetic disorder that carries his name – the Loeys-Dietz syndrome — which is a multisystem disorder caused by mutations in the genes encoding transforming growth factor beta (TGF-) receptor 1 or 2. While this syndrome is primarily characterized by connective tissue abnormalities, we have more recently found that an extraordinarily high proportion of these patients have severe allergic disease, usually including multiple food allergies, and other immunologic abnormalities. Dr. Guerrerio has therefore undertaken extensive clinical and laboratory studies of Loeys-Dietz syndrome and is collaborating with Dr. Dietz on studies of a newly developed mouse model of the disease.

Neal Halsey, M.D., is Professor of Pediatrics at the Johns Hopkins University School of Medicine, Professor of International Health at the Johns Hopkins Bloomberg School of Public Health, and Director of the Hopkins based Institute for Vaccine Safety. His primary research efforts are directed toward childhood immunizations and in particular immunization safety. Over the past 5 years he and Dr. Wood have collaborated on a series of CDC funded projects related to hypersensitivity reactions to vaccines. The collaborations are ongoing and a new study was just recently initiated, in collaboration with both Drs. Wood and Barnes, on the immunogenetics of vaccine hypersensitivity, particularly gelatin allergy. Dr. Halsey has an extraordinary track record of training fellows from a wide range of disciplines. Nadia Hansel, M.D., M.P.H., is an Assistant Professor of Medicine in the Division of Pulmonary and Critical Care Medicine and Assistant Professor of Epidemiology at the Johns Hopkins Bloomberg School of Public Health. She is a rising star in asthma research where she focuses on asthma epidemiology and the genetic and environmental determinants of asthma severity and morbidity. She is an active collaborator with Drs. Matsui, Diette, Okelo, Barnes, and Breysse.

Shau-Ku Huang, Ph.D., is currently a Professor of Medicine in the Division of Allergy and Clinical Immunology. His research has focused on immunoregulation and molecular genetics of allergic diseases, with current studies focusing on immunoregulation of allergic responses, combining genomics, molecular and cellular approaches, as well as mouse models, to uncover the regulatory mechanisms of allergic inflammation and allergen-specific immunotherapy, and molecular genetic studies of allergic diseases, utilizing genetic mapping analyses and positional cloning studies of susceptibility genes for asthma and asthma-associated phenotypes. In addition, to complement the genetic mapping effort and to sort out the complexities of variable molecular and cellular interactions, he is conducting a series of functional genomic studies to identify and characterize differentially expressed genes in an effort to define differential and/or dysregulated expression of the allergic inflammatory gene network. Dr. Huang has provided an outstanding basic science laboratory for several pediatric fellows, most recently acting as the primary mentor for Dr. Trong Le.

Donald MacGlashan, M.D., Ph.D., is currently a Professor of Medicine in the Division of Allergy and Clinical Immunology. For the last 20 years, his laboratory has focused on understanding the regulation of secretion from human basophils and mast cells. As part of a long-standing NIH grant, he remains deeply involved in working out the mechanisms that down-regulate IgE-mediated reactions in these cells. Recent studies from his laboratory indicate that two forms of desensitization (specific and nonspecific) operate before or after, respectively, the activation of the receptor-associated kinase, syk. Current efforts seek to identify events preceding syk activation as well as events that lie between syk activation and the mobilization of cytosolic calcium. A more recently funded enterprise relates to the observation that IgE antibody controls the expression of the high affinity receptor for IgE on basophils and mast cells. There are some practical implications for this piece of cell biology, in particular how it relates to the success of anti-IgE antibody therapy, so he is examining several aspects of the process, particularly the mechanisms underlying the control of receptor expression by IgE. Dr. MacGlashan is the Principal Investigator for our NIAID Asthma and Allergic Diseases Research Center (AADRC) Grant on which Drs. Wood, Bochner, Saini, and Schroeder are co-investigators. He has been consistently involved in our fellowship training over his career, providing input and direction to virtually all of our laboratory studies.

Sande Okelo, M.D., is an Assistant Professor of Pediatrics in the Pulmonary Division. His research focuses on childhood asthma, particularly related to urban and underserved populations. He has proven to be a superb investigator and is currently collaborating with Drs. Matsui, Diette, Hansel, and Rand.

Cynthia Rand, Ph.D., is a Professor of Medicine in the Division of Pulmonary and Critical Care Medicine and of Psychiatry in the Division of Behavioral Psychology. Dr. Rand is an internationally recognized expert in the area of medication adherence. Her research interests focus on psychosocial factors associated with pediatric and adult adherence to asthma therapy, adherence interventions, patient-provider communication, and health disparities. She has collaborated extensively with Drs. Wood, Matsui, and Okelo and has been an enormous resource to many fellows in the design of clinical research projects. She was co-mentor with Dr. Wood for Dr. Sharma during his fellowship for a study of dietary and medication adherence in adolescents with food allergy.

Sarbjit Saini, M.D., is currently an Associate Professor of Medicine in the Division of Allergy and Clinical Immunology, as well as the co-director of the combined fellowship in Adult and Pediatric Allergy and Immunology. His research is focused on IgE receptor biology on mast cell and basophils, interests that evolved from his fellowship training with Dr. MacGlashan to his current independent and well-funded laboratory. As the pediatric training program director, Dr. Wood meets regularly with Drs. Saini and Adkinson to discuss the training program and the progress of both the pediatric and adult fellows. He is also a collaborator with Dr. Wood on a study of basophil activation in oral food challenges, as well as the NIAID Asthma and Allergic Diseases Research Center Grant.

John Schroeder, Ph.D., is currently an Associate Professor of Medicine in the Division of Allergy and Clinical Immunology. His laboratory focuses on mechanisms regulating cytokine/mediator release by IgE receptor-bearing cells, including mast cells, basophils, and more recently dendritic cells. His laboratory has established protocols for rapidly isolating large numbers of basophils at high purity from human blood, and for growing culture-derived mast cells from human progenitor cells, as well as a variety of assays and techniques that concurrently detect cytokines and mediators following a wide range of stimuli. Over the past 5 years we have established major collaborations with Dr. Schroeder on studies investigating the role that innate immunity plays in modulating allergic reactions. Particular emphasis relates to the Toll-Like Receptors (TLR) found on these cells and how microbial-derived ligands interacting with these receptors induce phenotypic changes and modify function in these cells. These techniques are now being studied in our clinical trials of oral and sublingual immunotherapy for food allergy. Among our fellows, Dr. Schroeder has played an integral mentorship role as the primary mentor for Dr. Guerrerio and as co-mentor for Dr. Le (with Dr. Huang).

Pamela Zeitlin, M.D., Ph.D., is currently Director of the Eudowood Division of Pediatric Respiratory Sciences and Deputy Director of the Institute for Clinical and Translation Research. Her research focuses on the role of chloride channels in inherited diseases of the respiratory tract and she co-directs the Johns Hopkins Cystic Fibrosis Therapeutics Development Network site. In her role as director of the Pediatric Clinical Research Unit, Drs. Wood and Matsui, as well as all of the fellows who are conducting clinical research, collaborate with Dr. Zeitlin on a regular basis.

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