Immunobiology

Anthony Bosco

Associate Professor, Immunobiology
Associate Research Scientist
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
520-621-9114

Work Summary

I am currently appointed as Associate Professor of Immunobiology, and Associate Research Scientist, Asthma and Airway Disease Research Center (A2DRC), College of Medicine, The University of Arizona. My main areas of expertise include immunology and systems biology/genomic data analysis in the context of respiratory disease, allergy, and various modalities of immunotherapy. My research program is underpinned by the concept that genes do not exist nor function in isolation, they function as components of an interconnected system. My lab has performed the first studies to identify allergen-induced and rhinovirus-induced gene network patterns that underpin the pathogenesis of asthma and related traits. The long-term goal of this work is to unlock the basic immune mechanisms and principles that govern the early origins of asthma and identify novel pathways for therapeutic intervention.

 

Research Interest

Associate Professor Anthony Bosco, PhD, is an expert in Immunobiology and Systems Biology. His research program is underpinned by the concept that genes do not exist nor function in isolation, they function as components of an interconnected system. Understanding the organization and behavior of these systems is an essential goal towards decoding the role of the immune system in health versus disease. Dr Bosco’s laboratory employs cutting-edge molecular profiling technologies and computational analyses to identify the gene networks that underpin the pathogenesis of asthma and allergic diseases. For instance, he discovered that children with severe asthma attacks can be divided into two molecular phenotypes called IRF7hi and IRF7lo. Notably, these phenotypes have distinct responses to bacterial lysate immunotherapy, which paves the way for the development of precision medicine approaches for the treatment or prevention of asthma attacks in children. He has also employed systems biology to understand how allergen-specific immunotherapies produce an effect in the body on a molecular and systems level to switch off allergies.

Katherine Rhodes

Assistant Professor, Immunobiology
Assistant Professor, BIO5 Institute
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-9963

Research Interest

Dr. Rhodes' research focuses on the mechanisms bacteria use to develop and maintain communities within mammalian hosts. She is particularly interested in how these factors dictate the outcome of host-bacteria interaction in human adapted Neisseria species. As a Postdoctoral fellow with Dr. Maggie So of BIO5, she is working on projects to 1.) Characterize the role of the Type IV Pilus in Neisseria colonization and persistence using a natural model of infection in mice 2.) Identify new host interaction factors required for Neisseria carriage, and 3.) Examine the impact of the female reproductive tract microbiota on Neisseria gonorrhoeae infection dynamics.

Justin Wilson

Assistant Professor, Immunobiology
Assistant Professor, Cancer Biology - GIDP
Assistant Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-7622

Research Interest

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.

Koenraad M Van Doorslaer

Associate Professor, Immunobiology
Assistant Professor, Virology
Assistant Professor, BIO5 Institute
Assistant Professor, Cancer Biology - GIDP
Assistant Professor, Genetics - GIDP
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-9585

Research Interest

Papillomaviruses (PVs) are a diverse family of dsDNA viruses infecting most, if not all, amniotes. Papillomaviruses infect cutaneous or mucosal epithelia. While most infections are self-limiting, persistent infection with specific human papillomaviruses has been shown to be the causative agent for cervical cancer. All established oncogenic HPV types belong to a single viral genus (the Alphapapillomaviridae). Of note, phylogenetically, these oncogenic HPV types cluster into a so-called high-risk (HR) clade, indicating an evolutionary relationship between these viruses. Importantly, not all HPV types within this HR clade are associated with cancer. I am intrigued by the observation that only a limited subset of human papillomaviruses is oncogenic. Throughout my studies I have used a combination of biochemical assays and computational analyses to understand why evolutionarily related viruses differ in their ability to cause cancer in humans. It is improbable that the ability to cause cancer provides papillomaviruses with an evolutionary advantage. It is likely that many of the viral functions linked to oncogenesis were evolutionarily beneficial as papillomavirus adapted to novel environmental niches on the host (e.g. external genitalia vs. cervix). Papillomaviruses have evolved to usurp the cellular machinery to complete their life-cycle. The papillomaviral lifecycle perturbs the normal differentiation cycle of the infected cell, forcing cells to divide far beyond their normal lifespan. It is feasible that the continued insult provided by replicating viruses eventually results in malignant transformation of the infected cell. However, while persistent infection is key to viral oncogenesis, many long-term persisting viruses do not cause cancer. By carefully interrogating the differences between these viruses, I believe it will be possible to elucidate which viral phenotypes are associated with oncogenic progression. The pathways targeted by these viruses may represent powerful targets for therapeutic intervention

Magdalene Yh So

Professor, Immunobiology
Director, Microbial Pathogenesis Program
Professor, Animal and Comparative Biomedical Sciences
Professor, Biochemistry/Molecular Biophysics
Professor, Genetics - GIDP
Professor, Molecular and Cellular Biology
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-3097

Work Summary

How do bacteria "talk" to the body? How does the body reply to the microbe? How does this conversation affect your health and well being?

Research Interest

Magdalene So, PhD, is a Professor in the Immunobiology Department and Director of the Microbial Pathogenesis Program at the University of Arizona College of Medicine. Dr. So is recognized internationally for her research in the microbial pathogenesis. Her research focuses on two medically important bacterial pathogens: Neisseria gonorrhoeae, which causes over 100 million new cases of sexually transmitted infections each year worldwide, and Neisseria meiningitidis, which frequently causes meningitis epidemics in Subharan Africa. Her goal is to understand on how these two pathogens cause disease, with the aim of applying this information to developing new antibiotics for treating these infectious agents and improving current methods of vaccine development. Dr. So recently expanded her research to the commensal species in the Neisseria genus. These bacteria are normal inhabitants of the body and are closely related to the two pathogenic species; but unlike their pathogenic cousins they do not cause disease. Dr. So’s new research effort seeks to determine the differences in behavior of commensal and pathogen Neisseria. Dr. So’s research approach is multidisciplinary, involving concepts and techniques in biophysics, bioinformatics, cell biology, biochemistry and genetics. Collaborators from institutions around the world contribute to this effort. Dr. So has published over 100 peer-reviewed research papers in internationally renowned journals, and over 20 reviews and book chapters. She holds several patents as a result of her research. She is frequently invited to speak at universities and national and international meetings. She is a member of the American Academy of Microbiology, an elected body, and serves on the scientific boards of several research centers. Over the course of her career, Dr. So has trained over 44 postdoctoral fellows and graduate students. The majority of her trainees are internationally recognized researchers in their own right. Keywords: Infectious disease, microbiology

John G Purdy

Associate Professor, Immunobiology
Research Fellow, BIO5 Institute
Associate Professor, Cancer Biology - GIDP
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-4371

Work Summary

All viruses hijack host cell machinery to facilitate their replication. My lab investigates how the production of infectious viral progeny relies on host metabolism. Our overall goal is to guide the development of novel antiviral therapies using information regarding how viruses hijack host metabolism.

Research Interest

All viruses hijack host cell machinery to facilitate their replication. Producing infectious viral progeny relies on host cell metabolic pathways to provide energy and building blocks such as nucleotides, amino acids, and lipids. I am interested in investigating the molecular remodeling of cellular metabolic and lipid environments by viruses. The overall goal of my research in dissecting the complex virus-host metabolism interactions is to guide the development of novel antiviral therapies. Keywords: Infectious Disease, Virology, Metabolism, Lipidomics

Janko Nikolich-Zugich

Department Head, Immunobiology
Co-Director, Arizona Center on Aging
Professor, Immunobiology
Professor, Medicine
Professor, Nutritional Sciences
Professor, Genetics - GIDP
Professor, Neuroscience - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-6065

Research Interest

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.

Michael S Kuhns

Associate Professor, Immunobiology
Associate Professor, Genetics - GIDP
Associate Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-6461

Work Summary

Michael Kuhns' research program is focused on (i) increasing our basic understanding of how T cell fate decisions are made (e.g. development, activation, differentiation, effector functions), and (ii) increasing their working knowledge of how to manipulate these decisions to direct T cells towards a desired outcome, such as increasing responses to vaccines or tumors, preventing transplant rejection, or attenuating autoimmunity.

Research Interest

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.

Michael D L Johnson

Associate Professor, Applied BioSciences - GIDP
Associate Professor, BIO5 Institute
Associate Professor, Immunobiology
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-3779

Work Summary

Metals such as calcium and iron are essential to living organisms. Some metals in excess, like copper, are detrimental to bacteria. My laboratory studies this phenomenon in Streptococcus pneumoniae to find novels method for killing pathogenic bacteria.

Research Interest

Metals serve as vital nutrients to all biological systems. During infections, bacteria must not only acquire all metals necessary for survival from within the host, such as calcium or manganese, but must also efflux metals that are toxic or in excess such as copper. The overall goal of my laboratory is to investigate how bacteria maintain homeostasis within the metal milieu. This goal involves determining how metals are processed, the orchestrated response during metal sensing, and the role that the host plays in this process during infection. Understanding how bacteria interact with metals during infections will identify novel therapeutic strategies against bacterial infections. Keywords: Infectious Diseases, Antibiotic resistance, Bacterial Pneumonia

Felicia D Goodrum Sterling

Interim Associate Department Head, Immunobiology
Member of the Graduate Faculty
Professor, BIO5 Institute
Professor, Cancer Biology - GIDP
Professor, Cellular and Molecular Medicine
Professor, Genetics - GIDP
Professor, Immunobiology
Professor, Molecular and Cellular Biology
Primary Department
Department Affiliations
Contact
(520) 626-7468

Work Summary

Dr. Goodrum's long-standing research focus is to understand the molecular virus-host interactions important to human cytomegalovirus (CMV) latency and persistence in the host. She has focused on identifying viral and host determinants mediating the switch between latent and replicative states. The goal of her research program is to define the mechanistic underpinnings of HCMV latency and reactivation to lay the foundation for clinical interventions to control CMV disease in all settings.

Research Interest

Felicia Goodrum earned her Ph.D. from Wake Forest University School of Medicine studying cell cycle restrictions to adenovirus replication. She trained as a postdoctoral fellow at Princeton University in the laboratory of Dr. Thomas Shenk studying human cytomegalovirus latency. Dr. Goodrum joined the faculty at the University of Arizona in 2006. Dr. Goodrum is the recipient of the Howard Temin Award from the National Cancer Institute, the Pew Scholar in Biomedical Sciences Award, and the Presidential Award for Early Career Scientists and Engineers.Dr. Goodrum's research focuses on the complex host-virus interactions that result in viral persistence. Progress in understanding latent programs of persistence have been impeded by the inherent complexity of the herpesviruses and that paucity of adequate model systems. Herpesviruses are extraordinary for their ability to coexist with their host by establishing life-long latent infections. Latency is defined as a reversibly quiescent state during which viral gene expression and replication is highly restricted. Her laboratory studies cytomegalovirus or CMV, one of eight human herpesviruses. CMV is remarkable in that it persists latently in 60-99% of the population, generally in the absence of disease in the immunocompetent host. Reactivation of CMV from latency poses life-threatening disease risks in immunocompromised individuals, particularly transplant patients. CMV infection is also the leading cause of infectious disease-related birth defects, affecting ~1% of live births in the US. Further, the health cost of the latent coexistence of CMV is just beginning to emerge in an association to age-related pathologies including vascular disease, immune dysfunction and frailty. The key to eradicating CMV lies in understanding latency in order to ultimately develop novel antiviral strategies targeting latently infected cells or to prevent reactivation. Our studies aim to define the molecular basis of persistence by defining viral and cellular determinants important to viral persistence and the mechanisms by which these determinants function in relevant cell models. In turn, our work will provide critical insights into how CMV assimilates into and impacts human biology.