Immunology

Dr. Fernando D. Martinez is a Regents’ Professor and Director of the Asthma & Airway Disease Research Center at the University of Arizona in Tucson. Dr. Martinez is a world-renowned expert, and one of the most highly regarded researchers, in the field of childhood asthma. His primary research interests are the natural history, genetics, and treatment of childhood asthma. His groundbreaking research has had an impact on his field in numerous ways, most prominent among them the development of the concept of the early origins of asthma and COPD. This concept is now widely accepted as the potential basis for the design of new strategies for the prevention of these devastating illnesses affecting millions of children and adults worldwide. In addition, Dr. Martinez has made important contributions to our understanding of the role of gene-environment interactions in the development of asthma and allergies. He has also been the principal investigator of one of the Clinical Centers that are part of the NHLBI Asthma Treatment Networks, which have contributed fundamental new evidence on which to base national guidelines for the treatment of the disease. Dr. Martinez currently serves on national scientific boards including the NHLBI National Advisory Council and the National Scientific Council on the Developing Child. He was a member of the National Asthma Education and Prevention Program that was responsible for the development of the Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma in 1997 and its first revision in 2001. He also has been a member of the FDA Pulmonary-Allergy Drugs Advisory Committee and the Board of Extramural Advisors of the National Heart, Lung, and Blood Institute (NHLBI). Dr. Martinez’s research and vision are well detailed in more than 250 original research papers and editorials, many in collaboration with investigators from all over the world. He is frequently invited to give keynote presentations at national and international meetings.

Lonnie Lybarger, PhD, is an Associate Professor in the Department of Cellular and Molecular Medicine within the College of Medicine at the University of Arizona. Dr. Lybarger’s research program focuses on the mechanisms that regulate the activation of immune responses. In particular, his group studies a process known as antigen presentation, which is central to many aspects of the immune response against pathogens and tumors. This work includes detailed analyses of the cell biology of antigen presentation, as well as the study of its impact on immune responses. Recently, Dr. Lybarger has begun to study the critical link between antigen presentation and the regulation of metabolic homeostasis, with relevance to conditions such as type II diabetes.Research in the Lybarger lab has been funded by grants from State and National agencies. He has been an author/co-author on ≈35 original research reports, with his major contributions coming in the field of antigen presentation. Many of these reports involve collaborations within the University of Arizona and with colleagues at other institutions. Dr. Lybarger has served as a reviewer for University and National granting agencies, as well as reviewing for many research journals. In addition, Dr. Lybarger has served as a primary research advisor to a number of graduate and undergraduate students, while contributing to the classroom instruction of medical and graduate students.

Dr. Ledford’s current work in the area of pulmonary surfactant immunobiology combines her knowledge of mouse genetics, pulmonary disease models and immune function regulation and focuses on understanding the role of Surfactant Protein-A (SP-A) and how it regulates signaling pathways within various immune cell populations. Specifically, she is interested in how SP-A regulates degranulation, either directly or indirectly, of two important cell types in asthma: mast cells and eosinophils. More recently, Dr. Ledford’s research has focused on understanding how genetic variation within human SP-A2 alters functionality of the protein in relation to eosinophil activities and how this translates to characteristics observed in human asthma.

What we’re interested in: For all vertebrates, from mice to humans, vaccine-induced and naturally primed immunity to pathogens require that coordinated, multi-cellular responses emerge from a myriad of ‘conversations’ that take place between cells of the immune system. These conversations occur via cytokines and chemokines that are secreted by one cell and detected via receptors on other cells. They also occur via direct contacts between membrane-bound molecules at the interface between two cells. Ultimately, these conversations are responsible for insuring that an appropriate immune response occurs in the appropriate place, and at the appropriate time, to fight an infection without inducing an inappropriate response to commensal organisms or self-antigens. The molecules on T cells that are involved in these conversations include but are not limited to: the T cell receptor (TCR), which provides clonotypic antigen specificity to T cells; the CD3δε, γε, and ζζ signaling dimers that connect the TCR to the intracellular signaling machinery; the CD8 and CD4 coreceptors that provide major histocompatibility molecule (MHC)-restriction for T cells that recognize antigenic peptides bound to class I or II MHC, respectively; and costimulatory molecules, such as CD28, that provide information about the activation state of an antigen presenting cell (APC) and thus the context in which an antigen occurs. We are interested in understanding how the individual contributions from this chorus of molecules are integrated to achieve the critical balance between tolerance of self-antigens and protective immunity against pathogenic infection. Specifically, we are working to understand how the information that is critical for T cells to decide if and how they should respond to antigen is conveyed from an antigen presenting cell (APC) to a T cell. We are using a variety of classic molecular, cellular, and biochemical techniques, as well as more modern live cell imaging approaches, to probe the molecular mechanisms involved in these processes. We are also developing mouse model systems to determine how individual mechanisms contribute to T cell responses in vivo during pathogenic infection or autoimmunity. Altogether, our work is aimed at increasing our basic and practical appreciation of T cell responses and regulation.

Dr. Emmanuel Katsanis, MD, and his laboratory conduct basic and translational research aimed at advancing new cancer immunotherapeutic strategies. His expertise is in stem cell transplant immunology, cellular therapy, and cancer vaccine approaches.Immunity against tumors depends on complex innate and adaptive immune responses that involve the sequential mobilization of 'messenger' and 'killer' immune cells. However, despite the arsenal harbored by the immune system to ensure tumor immunosurveillance, cancers can escape immune detection and elimination. Current research in the laboratory is evaluating immuno- and chemo-immunotherapeutic strategies to promote anti-tumor immune responses following bone marrow transplantation, while investigating approaches to mitigate graft versus host effects. Keywords: Cancer Immunology, Hematopoietic Cell Transplantation

Melissa Herbst-Kralovetz, PhD is an Associate Professor in the Departments of Basic Medical Sciences and Obstetrics and Gynecology and is Director of the Women's Health Microbiome Initiative at the UA College of Medicine-Phoenix. The Herbst-Kralovetz research lab is broadly interested in understanding innate mucosal immune responses to resident bacteria, pathogens (e.g HSV-2), and microbial products at mucosal sites, including the female reproductive tract. The mucosa provides a major immune barrier (physical, biological, and chemical) to microbial insult and her lab is interested in studying the mucosal barrier function of the lower female reproductive tract and its role in host defense against infection and inflammation as well as maintaining mucosal homeostasis. Dr. Herbst-Kralovetz has a long-standing interest and background in studying infections/conditions that impact women’s health.

The Doyle lab investigates the role of the immune system in causing dementia after stroke. Up to 30% of stroke patients develop dementia in the months and years after their stroke and we are testing the hypothesis that in some patients this is due to a chronic inflammatory response that persists at the site of the stroke infarct. We suspect that in the weeks, months and possibly years after stroke, neurotoxic inflammatory mediators, including T cells, cytokines and antibodies, leak out of the stroke infarct and cause bystander damage to the surrounding tissue, which then both impairs recovery, and in some instances leads to cognitive decline. In support of this hypothesis we have data that demonstrates that inflammation persists for months at the site of the infarct after stroke, and that a single stroke can directly lead to the development of immune-mediated delayed cognitive deficits. We are currently in the process of targeting different components of the prolonged inflammatory response to stroke to determine if post stroke dementia can be treated by selectively ablating individual immune mediators such as B lymphocytes, T lymphocytes, and CCR2. Keywords: Neuroinflammation, stroke, dementia, Alzheimer's disease

Elizabeth Connick, M.D.'s laboratory focuses on the immunopathogenesis of HIV infection, particularly strategies employed by the virus to evade cellular immunity. Because most HIV replication occurs in secondary lymphoid tissues, much of her work has been focused on understanding the biology of HIV replication within lymphoid tissues and unique features of the host immune response at those sites. Other areas of interest include investigation of sex differences in HIV-1 infection as well as factors that promote accelerated cardiovascular disease in HIV-infected individuals.

Our research group studies the interface between the immune system and the world around us, on us, or within us. My work seeks to study the complex molecular language that our immune system uses to sense the world. The immune system recognizes microbes (pathogens & commensals), allergens, mutated genes in cancerous cells (neo-antigens), transplanted tissues (allo-antigens), and sometimes accidentally recognizes and responds to our own bodies in the setting of autoimmune disease. The goal of my group is to use genetic and computational tools to discover the rules for this recognition process. Keywords: Immunology, Immuno-Informatics, Infectious Disease, Autoimmunity

Dr. Scott Boitano Ph.D., is a Professor of Physiology, Cellular and Molecular Medicine, the BIO5 Institute and Associate Research Scientist of the Arizona Respiratory Center. Dr. Boitano received a B.S. in Plant Biology from University of California; Berkeley and a Ph.D. in Genetics & Cell Biology from Washington State University. Dr. Boitano’s primary research interest is in cell respiration. This encompasses the analysis and observation of cell physiology, cell-cell communications and cell-pathogen interactions. Dr. Boitano’s research pertains to the upper airway epithelium is an active cellular layer with ciliary movement to clear materials, the ability to secrete inflammatory effectors, and a biological barrier function that helps protect against pathogenic microorganisms, foreign insults and injury. Although much is known concerning the microbial genetics and microbial signaling of infection by Bordetella, relatively little is known about host cell pathology after exposure to Bordetella. Individuals have a primary tissue culture system that serves as an in vitro model of airway cell signaling and communication, and a battery of B. bronchiseptica strains, some of which are mutant in key factors shown to inhibit their ability to establish infection in animal models. His research goal is to define specific pathogen factors that alter host cell physiology to initiate or overcome host cell defense. The Boitano lab also analyzes the layers of the alveoli of the distal mammalian lung. Minimal information is known about this subject and Dr. Boitano believes that this model system for alveolar intercellular communication could expedite the formulating and testing of new medical treatments for dysfunctional alveolar cell physiology that underlies specific airway conditions following disease, insult and injury in the lung.