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 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.

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.

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. 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.

Gregory Diette, MD, M.P.H., is a 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.

Harold Dietz, M.D., is 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.  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.

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. 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.

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. He has been consistently involved in our fellowship training over his career, providing input and direction to virtually all of our laboratory studies.

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 been an enormous resource to many fellows in the design of clinical research projects.

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 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 five 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.