Immunology

My approach to infectious diseases has always been multi-disciplinary. There is a constant arms race between both host and pathogen. Infection changes the host response and the host response exerts changes on the pathogen. Approaching these problems from a single host or pathogen centric view limits the chance for complete understanding. Most of my published works have been in the interface between both the host and the pathogen. Joining Bio5 will allow me to join other scientist interested in multi-disciplinary answers to complex questions.

Dr Tara Carr is a board certified Allergist/Immunologist physician with subspecialty training and experience in the evaluation and treatment of allergic and immunologic diseases in both children and adults. She is focused on studying the impact of environmental exposures on development and heterogeneity of allergic disease, with an emphasis on asthma. She has significant clinical research experience in pediatric and adult allergic disease and asthma within the Asthma & Airway Disease Research Center at the University of Arizona. She has led multiple industry trials at the research center as primary investigator, in areas of severe asthma, nasal polyps, and food allergy. She has also been a sub-investigator within three large NHLBI-funded clinical research networks in asthma (PrecISE, AsthmaNet, American Lung Association-Airway Clinical Research Centers), and served as a clinical core co-director for the Dysfunction of Innate Immunity in Asthma U19 program. Her roles include leadership of the research team, recruitment of participants, and oversight of procedures and adverse reactions among those participants. At Bio5, Dr Carr leads the immunology and genetics laboratory responsible for receiving all samples collected as part of these studies, processing those samples for future use, biobanking those samples in a longitudinal repository, and running various experiments on those samples as necessary for the planned study. A sub-investigator in the Tucson Children’s Respiratory Study, Dr Carr is contributing to longstanding efforts toward understanding early life risk factors of lung disease by leading metabolic, allergic, and immunologic analyses of longitudinally collected samples. As co-investigator for the Binational Early Asthma and Microbiome Study, Dr Carr leads the scientific effort to collect, transport, and store human and environmental samples from Nogales Mexico and Tucson. Dr Carr is responsible for describing the immunology of pregnant women and the immunological development of their babies, with a goal of understanding which maternal and environmental factors influence allergic (asthma-prone) and non-allergic immune development.
To this end, Dr Carr’s lab utilizes a broad range of experimental methods- often in collaboration with other Bio5 researchers- to describe the biological characteristics of asthma and allergic disease, including DNA and RNA sequencing, protein measurement by ELISA, Immulite and Luminex, culture and stimulation of peripheral blood mononuclear cells with cellular phenotyping, and metabolomics.

David Baltrus (PhD) is broadly interested in understanding how bacterial evolution is shaped by interactions with other organisms. Questions investigated by the Baltrus lab range from asking how evolutionary events such as the transfer of genes between microbes affects the development of antibiotic resistance to testing how microbiomes impact the development and physiology of plants and animals. The lab approaches these questions by using a variety of existing tools, from screening for mutants using "toothpicks and agar plates" to experimental evolution to comparative genomics. However, Dr. Baltrus is also highly interested in developing new tools that enable sequencing and tracking of bacterial populations and communities of interest (like potential pathogens) in real time under natural conditions.

I am an Associate Professor in the department of Nutritional Sciences (College of Agriculture and Life Sciences) at the University of Arizona and hold joint appointments in Pediatrics (College of Medicine) and Immunobiology (College of Medicine). I am also part of the mentoring team for the Physiological Sciences and Cancer Biology Graduate Interdisciplinary Programs, which recruit students who are continuing in education. My research interests are concerned with the effects of aging, stress and exercise on the immune system, and the role of adrenergic receptor signaling on immune cell redistribution and activation. Major focus areas include understanding (1) how exercise and other behavioral interventions can offset age-related decrements in the normal functioning of the immune system (immunosenescence), (2) how adrenergic receptor signaling can be used to improve cellular products for hematopoietic stem cell transplantation and immunotherapy, (3) the interplay between the immune and neuroendocrine system during high level human performance and extreme isolation (i.e. space travel), and (3) how persistent virus infections such as cytomegalovirus (CMV) can alter the phenotype and function of T-cells and NK-cells to protect the host from certain hematological malignancies. My current research is supported by NASA, the NIH (National Cancer Institute) and industry. I am a fellow of the American College of Sports Medicine (ACSM) and an honorary board member of the International Society of Exercise Immunology (ISEI). I am an active member of the Pychoneuroimmunology Research Society (PNIRS) and the Society for Immunotherapy of Cancer (SITC) and sit on the editorial board of the following scientific journals: Brain, Behavior and Immunity; Exercise Immunology Reviews (Associate Editor); Immunity and Ageing; American Journal of Lifestyle Medicine.

The innate immune system has a large repertoire of receptors/sensors that respond to microbial components and host “danger signals” in order to regulate inflammation and immune responses. The dysregulation of many of these sensors has been linked to chronic inflammatory disorders (e.g., inflammatory bowel diseases) and multiple types of cancer. My group’s research focuses on how the dynamic relationship between the intestinal microbiota and these innate immune sensors regulate the cell signaling events driving chronic inflammation and cancer development. We seek to treat these diseases through the manipulation of intestinal microbial ecology and redirection of immune activation.

Jean M. Wilson, Ph.D. is a Professor of Cellular and Molecular Medicine at the University of Arizona and member of the Arizona Cancer Center. Dr. Wilson’s work focuses on the establishment and maintenance of the mucosal barrier of the intestine. The cells of the intestine provide a selective barrier to pathogens and toxins, and loss of this barrier function is fundamental to pathologies such as inflammatory bowel disease and bacterial infection. In addition, loss of cellular interactions important for barrier function may predispose these cells to cancer. Work in Dr. Wilson’s laboratory focuses on a protein that is highly expressed in developing intestine, implying a critical role in the formation of the intestinal epithelium. Disruption of this protein compromises junctional integrity and epithelial polarity. Furthermore, expression of this protein is decreased in a model of neonatal necrotizing enterocolitis, a disease of newborns with high morbidity and mortality. These findings implicate this protein in the maintenance of intestinal barrier function in the neonate. In addition, continued expression in the adult intestine positions it to regulate epithelial permeability and polarity throughout life. Our studies focus on protein partners that interact with this protein with the goal of identifying the molecular machinery that regulates this pathway.

Donata Vercelli, MD, is a Professor of Cellular and Molecular Medicine, the Associate Director of the Arizona Respiratory Center and the Director of the Arizona Center for the Biology of Complex Diseases. Her research work is at the cutting edge of the immunology and genetics of complex lung diseases. Her laboratory spans both human and animal models. After characterizing cellular and molecular events critical for the regulation of human IgE synthesis, she became interested in the mechanisms through which natural genetic variants modify susceptibility to complex diseases, particularly allergy and asthma. To this purpose, she developed innovative, unique mouse models in which distinct human haplotypes of asthma- and allergy-associated genes are carried by BAC transgenic mice and can be directly compared for their regulatory properties in vivo. The unexpected, essential mechanisms underpinning the involvement of Th2 cytokines in allergy and asthma revealed by this mouse model have been fully validated in human populations. Dr. Vercelli's work on the epigenetic regulation of Th2 cytokine expression in human neonatal T cells revealed novel facets of early life regulatory events and her continued interest in epigenetics has led to the first demonstration that neonatal DNA methylation signatures in innate immunoregulatory pathways predict asthma during childhood. Most recently, Dr. Vercelli has devised a highly innovative approach that combines epidemiologic, biochemical and mouse model studies to dissect the mechanisms underlying the asthma-protective and asthma-promoting effects of two distinct US farming environments (Amish and Hutterite). Such studies are likely to critically advance our knowledge about fundamental mechanisms of asthma pathogenesis.

Vercelli Lab Website

Dr. Monika Schmelz is a Assistant Professor of Pathology and Member of the University of Arizona Lymphoma Consortium. Dr. Schmelz pursuing research on mechanisms for immune escape in aggressive lymphoma with poor survival rates. Dr. Schmelz received a 2 year award (2013-2015) from The Hope Foundation to study how tumor cells escape immunosurveillance, which is a hallmark of cancer, in aggressive diffuse large B-cell lymphoma (DLBCL) with poor patient outcome, and how immunosurveillance can be manipulated for therapeutic purposes. ( see also link: http://pathology.arizona.edu/news/dr-monika-schmelz-recipient-2013-swog-development-award). Dr. Schmelz also is pursuing biorepository science. She received a multi-million dollar award for hosting the Biorepository for a NCI funded clinical trial. ANCHOR is a multi-site phase III clinical trial entitled “Topical or Ablative Treatment in Preventing Anal Cancer in Patients with HIV and Anal High-Grade Squamous Intraepithelial Lesions”. 17,385 participants will be screened to identify and to enroll 5,058 eligible participants. An estimated 314,535 biospecimens over the duration of the clinical trial (8 years) will be collected and sent to Dr. Schmelz's lab. The biorepository is an extremely important factor for the outcome of this clinical trial, since correlative translational studies on biomarkers for early detection of anal cancer development in these specimens are planned by the NCI. Keywords: Cancer, Diffuse Large B-Cell Lymphoma (DLBCL), Therapeutic Biomarkers

My research program lies in one more focused and two broad and interconnected areas of aging research and intervention. a. Infection and immunity with aging. Over the past 15 years my group has systematically investigated alterations with aging of the immune system and its interactions with acute and persistent microbial pathogens. In the process, we have discovered and described multiple and cumulative defects in microbial detection, initial recognition and uptake by the innate immune system, processing, presentation and initiation of the adaptive immune response, generation of effector immunity and of memory responses and homeostasis and long-term regulation of lymphocyte subsets. We have followed up that work with attempts to correct molecular and cellular defects using novel vaccination and thymic rejuvenation models in mice and non-human primates, and by validating the observations from these models in humans, as well as deriving primary data from human subjects on these same topics. . There is no doubt that I will continue this work on both tracks: primary, basic research will be performed in the mouse, human or NHP model, and, depending on suitability, may be also validated in other models. Translation will be performed in human or NHP models, where we will seek to intervene therapeutically to improve outcomes of infection in older adults. The ultimate goal for the next decade of my career and beyond will be to produce palpable improvement in the immune system of older adults so as to increase success of vaccination and resistance to infection. b. Inflammation in aging: causes and consequences. This is a broader interest of mine, that intersects not only with the immune system, but also with microbial colonization, gut barrier function, metabolism, adiposity and energy sensing. Why do older adults exhibit increased signs and markers of systemic inflammation? Is this inflammation multifactorial, or does it lie in an overexcitable immune system, or increased proinflammatory adipose mass or altered microbial colonization and increased permeability of different (mostly mucosal) barriers? Or a combination thereof? Can we conclusively intervene against diseases of aging and, perhaps, normal aging itself, by modulating inflammation? Microbiome sequencing, deliberate colonization with specific microflora, depletion of different immune cell subsets and/or antibiotic and anti-inflammatory treatments as well as metabolic intervention will all be combined to understand and treat these conditions and their impact upon aging. c. Interventions to extend healthspan and longevity. Advances in the biology of aging have now reached the point where it is no longer unrealistic to put the incredible promise of health-prolonging anti-aging intervention to use in humans. One must: (i) understand effects of life extension in model organisms upon healthspan and end organ function; (ii) carefully dissect signaling pathways that lead to the measured outcomes and validate them in higher primates or humans; and (iii) intervene along these pathways to apply life and healthspan extension treatments. We are currently in the process of multidisciplinary collaborative studies to understand end-organ function and quality of life in the course of different mTOR pathway manipulations in adult and aged mice. Drug discovery program will follow to optimize treatments, and translation will be attempted subsequently in primates and humans.