Health

Kristen Pogreba Brown, Ph.D., M.P.H., is an assistant professor of epidemiology at the University of Arizona Mel and Enid Zuckerman College of Public Health. Prior to joining the faculty, Dr. Pogreba-Brown was an Epidemiologist with the College as the director of the Student Aid for Field Epidemiology Response (SAFER) team. In addition to continuing to oversee the SAFER program, her research projects are focused on foodborne diseases and improving methodology to respond to outbreak investigations. She is currently working on a project to identify the risk factors related to foodborne infection as well as the risk factors related to specific chronic outcomes following acute disease. She has recently initiated a One Health Program at the University to form collaborative research teams from across campus and develop a graduate level certificate program. She is also actively involved in public health preparedness activities, specifically for large events. Dr. Pogreba-Brown works with various county health departments in Arizona as well as the state health department to aid in outbreak investigations and serves on the state’s Foodborne Taskforce Committee.

I have spent the past 21 years of his research career studying the properties of insulin-secreting tissue and their relationship to viability and function. I have worked on the development and validation of assays (especially ones based on mitochondrial function such as oxygen consumption rate) for the real-time, objective assessment of islet quality prior to transplantation. In particular the assay based on oxygen consumption rate has been recently validated based on its ability to predict diabetes reversal in mice and clinical human islet auto transplants in patients with chronic pancreatitis. I have used these assays along with engineering principles to optimize the islet transplantation process from pancreas procurement to islet infusion to the recipient. My group has also developed tools for the real time non-invasive assessment of pancreases and other organs during preservation, and i am actively involved in research for improvements in organ preservation technology aiming at extending the allowable time window from procurement to transplantation and the utilization of organs from expanded criteria donors without compromising clinical outcomes. I have had continuous NIH funding for the past 7 years in the area of pancreas preservation and I have spearheaded the effort for the development of humidified oxygen gas perfusion (persufflation) of the pancreas using novel technology for portable in situ oxygen generation from water via electrochemistry. I am also actively collaborating with leaders in the liquid perfusion field on NIH sponsored projects aiming at improving oxygenation.

David Nix, PharmD, joined the Department of Pharmacy Practice and Science in July, 1996. He will be teaching pharmaceutical calculations this fall as well as beginning practice and research activities. He completed a research fellowship in infectious disease pharmacotherapy in Buffalo, New York. Prior to joining the department, he worked at the Clinical Pharmacokinetics Laboratory at Millard Fillmore Hospital in Buffalo as an associate director since 1995 and as assistant director since 1989.

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.

Research Interests Our objective is to define how integrin interactions within the tumor microenvironment impact prostate cancer development, hormonal resistance, and metastasis. Our approach is to understand the normal biology of the prostate gland and its microenvironment, as well as the bone environment, to inform on the mechanisms by which tumor cells remodel and use that environment to develop, acquire hormonal resistance, and metastasize. Our research is focused in three primary areas: 1) developing in vitro and in vivo models that recapitulate human disease based on clinical pathology, 2) identifying signal transduction pathway components that could serve as both clinical markers and therapeutic targets, and 3) defining the genetic/epigenetic programming involved in prostate cancer development.

Katrina Miranda, PhD, claims nitric oxide (NO), which is synthesized in the body via enzymatic oxidation of L-arginine, is critical to numerous physiological functions, but also can contribute to the severity of diseases such as cancer or pathophysiological conditions such as stroke. This diversity in the responses to NO biosynthesis is a reflection of the diverse chemistry of NO. For instance, NO can alter the function of enzymes by binding to metal centers. This type of interaction could result in outcomes as disparate as control of blood pressure or death of an invading bacterium. NO can also be readily converted to higher nitrogen oxides such as N2O3 or ONOOH, which have very different chemical and biological properties. The ultimate result will depend upon numerous factors, particularly the location and concentration of NO produced. Therefore, site-specific modulation of NO concentration offers intriguing therapeutic possibilities for an ever expanding list of diseases, including cancer, heart failure and stroke. As a whole, Dr. Miranda is interested in elucidating the fundamental molecular redox chemistry of NO and in developing compounds to deliver or scavenge NO and other nitrogen oxides. These projects are designed to answer questions of potential medical importance through a multi-disciplinary approach, including analytical, synthetic, inorganic and biochemical techniques.The project categories include five major disciplines. First, she will work on the development and utilization of analytical techniques for detection and measurement of NO and other nitrogen oxides as well as the resultant chemistry of these species. Second, she will synthesize potential donors or scavengers of NO and other nitrogen oxides. Third, it’s necessary to describe chemical characterization of these compounds (spectroscopic features, kinetics, mechanisms and profiles of nitrogen oxide release, etc.). Fourth, Dr. Miranda will try to describe the biological characterization of these compounds (assay of effects on biological compounds, mechanisms and pathways, in vitro determination of potential for therapeutic utility, etc.). Fifth, she will identify of potential targets, such as enzymes, for treatment of disease through exposure to nitrogen oxide donors. Keywords: cancer treatment, pain treatment

Over the last two decades my work has focused on developing computational platforms and enabling technologies, primarily directed towards improving research productivity and collaboration for interdisciplinary teams and virtual organizations. The key thrust areas for my work encompass life cycle management for: 1. High throughput and automated bio sample processing systems 2. Highly scalable data and metadata management systems 3. High throughput and performance computing systemsMy recent work has been directed towards supporting pervasive computing needs for mHealth (mobile health) initiatives and health interventions, with focus on developing study management platforms that leverage cloud based telephony, messaging and video in conjunction with wearable’s and sensors.Platforms and tools developed by team are utilized in: 1. Managing samples and data for Clinically certified (CAP/CLIA) NGS pipelines 2. Large scale genotyping (million+ samples) with robotic automation 3. National Cyberinfrastructure iPlant; facilitates researchers to effectively manage their data, computation and collaborations using a cohesive computational platform 4. Health interventions and patient monitoring I firmly believe that measured adoption of emerging computational technologies and methods are essential for life scientist to successfully operate at the scale and complexity of data they are constantly encountering. This can only happen if there is continuing education and practical training focused around the use of Cyberinfrastructure and computational thinking. I have developed and taught workshops, graduate and undergraduate project based learning courses with emphasis on these topicsMy team (Bio Computing Facility) engages with the campus community at various levels ranging from multi- institutional collaborative projects, graduate and undergraduate courses for credit and special topic seminars and workshops. With emphasis on enabling digital discoveries for the life sciences.

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.

Public Relevance Statement: Can you imagine having a mouthful of canker sores and cavities? Thousands of head and neck cancer patients suffer these consequences from radiation treatment. The Limesand lab works to prevent these side effects thereby improving patients' quality of life. Clinical Relevance: Radiation therapy for head and neck cancer causes adverse secondary side effects in the normal salivary gland including xerostomia, oral mucositis, malnutrition, and increase oral infections. Although improvements have been made in targeting radiation treatment to the tumor, the salivary glands are often in close proximity to the treatment site. The significant destruction of the oral cavity following radiation therapy results in diminished quality of life and in some cases interruptions in cancer treatment schedules. Research Interests: My research program has its foundation in radiation-induced gland dysfunction; mechanisms of damage, clinical prevention measures, and restoration therapies. Evidence suggests that salivary acinar function is compromised due to apoptosis induced by these treatments and temporary suppression of apoptotic events in salivary glands would have significant benefits to oral health. We utilize a number of techniques in my laboratory including: genetically engineered mouse models, real-time RT/PCR, immunoblotting, immunohistochemistry, primary cultures, siRNA transfections, irradiation, and procedures to quantitate salivary gland physiology. Current project areas: 1. Radiation-induced apoptosis 2. Mechanisms of preserving salivary gland function 3. Identifying the radiosensitivity of salivary gland progenitor cells 4. Restoration of salivary gland function 5. Role of autophagy in radiation-induced loss of function