University Of Arizona

NIH Research Projects · FY 2025 · 1990-09

ABSTRACT Declines in spatial cognition and function of brain circuits responsible for these behaviors are among the hallmark signs of normative biological aging across species. The objective of this research program is to understand the basis of these age-related memory impairments. Rodent and nonhuman primate models can each provide a unique window into understanding how age impacts networks critical for cognition, at cellular resolution. These data can then be used to inform experiments conducted in humans to validate our predictions. The experiments proposed in the present application are guided by three primary aims. Aim 1 is to understand how brain circuits responsible for spatial cognition are altered in the aged rat. Two approaches are taken in this Aim to answer these questions. A novel spatial task is employed (the Instantaneous Cue Rotation task) that enables precise measurement of spatial behavior accuracy and representation updating in the rat. Additionally, simultaneous, dual-structure recordings from hippocampus and upstream entorhinal cortex will be conducted to identify age-related changes within the hippocampus proper that are driven by entorhinal cortical inputs, as well as changes in the entorhinal cortex driven by degraded hippocampal feedback signals. Aim 2 is to understand how hippocampal representations are altered in aged freely behaving nonhuman primates. Recent advances in wireless recording technologies enable new experimental designs for primates that can test directly the widely held assumption that circuit instability (“remapping”) in the aging rat will find an analogue in the aging primate brain. Free locomotion is a missing link between the behavioral conditions employed to study place cells in rodents, and head restrained, chaired conditions under which most studies are conducted in primates. Our hypotheses are that old monkeys will show faulty retrieval of hippocampal network patterns (similar to map retrieval failures in old rats) and that the global network activity state will be altered in both age groups when the animals are restrained, compared to when completely unrestrained and free to move. Aim 3 is to understand the neural underpinnings of navigation deficits in aged humans. High-resolution imaging will be employed to explore age-related alterations in both hippocampal subfield-selective ensemble codes as well as entorhinal cortex grid-like activity that may underlie navigation impairments. Highly immersive spatial environments that include locomotion will also be used to investigate the impact of age (young versus older adults) on the ability to maintain stable spatial representations during free exploration. Changes in representation stability in older adults would be consistent with inappropriate map retrieval observed in old rats. Taking advantage of new behavior and recording approaches in rodents and monkeys and novel high-resolution fMRI and virtual reality methods in humans, we believe significant advances will be made in our understanding of how circuits critical for spatial cognition are altered across age and species.

NIH Research Projects · FY 2024 · 1983-09

Abstract Our goal is to recruit, train and develop the next generation of leaders in cancer research. To achieve this objective, we will implement the Integrative Cancer Scholars (ICS) program as described in this competitive renewal of our long-standing Cancer Biology Training Program. ICS is an innovative predoctoral and postdoctoral fellows training program that embraces a paired-mentor team approach to maximize the impact and significance of cancer research. Specifically, Scholars choose one basic science mentor and one clinical science mentor from among nationally competitive basic and physician scientists. From the mentor pair, the Scholar selects a `lead' mentor from among the faculty with well-funded collaborative research programs with a broad range of cancer research specialties: Genomic and Epigenetic Instability, Tumor Microenvironment, Cancer Prevention and Control, Developmental Therapeutics, Cancer Imaging, Tumor Viruses and Immunology, Tumor Progression and Metastasis, and Cancer Pain. ICS is a unique program with distinct training events designed to integrate current molecular and clinical cancer concepts. Each Scholar is expected to conduct original cutting-edge research under the guidance of the mentor-pair and to participate in clinical cases with their chosen physician mentor. Progress of each trainee is ensured through compulsory committee meetings and annual evaluations by the mentor-pair. Scholars also participate in career development and national networking opportunities, including hosting thought leaders in our Cancer Biology Seminar Series, acquiring new targeted skills in educational workshops, and community engagement with oncologists and biotechnology experts. Additionally, Scholars are provided support to travel and present their work at a national meeting. ICS is associated with the Cancer Biology Graduate Interdisciplinary Program which provides instruction in cancer causation, epidemiology, prevention, and grant writing through specific coursework and a symposium featuring presentations of pre- and postdoctoral research. The postdoctoral training plan ensures that each trainee navigates a path of comprehensive training, leading to a mature scholarship and ability to conduct independent, cutting-edge research. The program is designed to expose each trainee to the range of current thought in the cancer field, to teach state-of-the-art laboratory techniques, to emphasize critical thinking skills, to introduce real-world aspects of clinical work, and to refine their career-development skills, particularly in networking, communication and grant/manuscript preparation. Pre- and postdoctoral researchers from laboratories of the participating mentors are eligible for ICS support, and Scholars are selected through a competitive process. Support from the UA, state-of-the-art research core facilities, and opportunities for underrepresented-minority researchers (UA is top of all Research I institutions for URMs in graduate school) round out a rich environment for training the future leaders of cancer research.

NIH Research Projects · FY 2025 · 1981-05

PROJECT SUMMARY/ABSTRACT (Description) Our multifaceted research training program, entering Year 40 at The University of Arizona (UA), introduces, trains and nurtures diverse medical students in health-related biomedical research and stimulates subsequent intensive and extensive research experiences. Building from the high level of student/faculty participation and outstanding record of trainee productivity (presentations, publications, awards, and advanced research), we will continue to offer a mix of 3-month experiences to 23-36 MS/year to engage in NHLBI-focused laboratory/clinical investigations fully integrated into our longstanding Curriculum on Medical Ignorance (CMI). CMI features an intensive Summer Institute on Medical Ignorance, year-round enrichment activities (e.g., seminars, clinical correlations, Failure/Pondering/Ethics Rounds, career advising), and advanced extracurricular research opportunities through a popular Research Distinction Track. Our unique Virtual Clinical Research Center/Questionarium online platform with evolving Precision Medicine Theme (“Translating Translation”) focuses on examples, scenarios, and steps in the translation process. CMI aims to foster attitudes and skills to address the vast shifting world of medical ignorance [i.e., "what we know we don't know (current research), don't know we don't know (future discovery), and think we know but don't (error)"] from molecular systems to clinical and community medicine. Questioning, critical/creative thinking, team building, mentorship, and leadership skills are cultivated to forge a mentoring “chain reaction” through a diverse, multilevel NIH-funded research pipeline continuum. Overseen by an experienced multidisciplinary administrative team, students choose projects across a spectrum of disciplines and investigations (in vivo, in vitro, in situ, in silico, molecular mechanisms, clinical trials, populations studies, and modeling approaches) that support NHLBI mission areas, encompassing the normal and disordered cardiovascular (CV) system, lung, blood, and sleep (cardiac contractility, development, hypertrophy, microcirculation, endothelial biology, electrophysiology, oxygenation, heart failure, resuscitation, CV genomics/proteomics, CV prosthetics, arterial/venous/lymphatic disease); pulmonology (asthma, cystic fibrosis, pulmonary hypertension, organogenesis, microbiome, sleep apnea); and cell-based science/therapy; with cross-cutting themes in data science/ bioengineering/multimodal imaging; drug/ device discovery R&D, risk factors, health disparities; and other topics of interest to student researchers and spanning translational steps from bench to bedside to clinical practice and population health. Based on a 40-year track record reflected in follow-up surveys of institutional impact and participant comes, we anticipate cultivating an enlarging number of scientific physicians who understand and contribute to the research enterprise and a growing cadre of physician- scientist leaders to replenish the dwindling supply of translational researchers. Detailed short-term and long-term formative/summative program/participant evaluation with database registry, individual development plans, and career portfolios will document efficacy and promote dissemination.

NIH Research Projects · FY 2025 · 1979-07

Environmental Health Sciences at the University of Arizona has a long-standing reputation for excellence in training Ph.D. and postdoctoral scientists, as evidenced by the fact that many of our graduates are leaders in academia, industry, and government. To this end, our graduate program has evolved from a systems-based toxicology experience to a curriculum in which students are trained to apply state-of-the art techniques to solve mechanisms of environmental toxicity affecting human diseases in various organ systems. Training of nine predoc and three postdoc students in the cutting-edge research programs of 29 Training Grant Faculty members are augmented by innovative technologies developed at the University of Arizona in association with the Southwest Environmental Health Sciences and BIO5 Centers. Additionally, translational approaches undertaken by our NIEHS Superfund Program and One Health Research Initiative provide an exceptionally stimulating environment for the training of graduate students and postdoctoral fellows. The interactive research of our Training Grant Faculty and our state-of-the-art Facility Cores extend the training environment from a single laboratory-oriented domain to a multidisciplinary experience strongly supportive of collaborative research. Current trainees are now selected through a university-wide competition and the UA Graduate College provides financial support for all first year Ph.D. students through an umbrella recruitment program, providing a large pool of highly qualified candidates for competitive selection of predoctoral trainees. Predoctoral training is achieved through a combination of coursework, laboratory research, and supplemental enrichment activities. Postdoctoral trainees participate in innovative research programs and are guided to develop professional skills in oral and written communication and leadership. Over the past five years, our curricular changes have paralleled the evolving expertise of the Training Grant Faculty. We have recruited six senior full Professors, two Associate Professors, and five junior Assistant Professors into the Training Grant, which significantly enhanced our core strengths in mechanistic-based molecular toxicology training. The request for continuation of NIEHS support is justified by the highly successful nature of our program, clear demand for our graduates, strong emphasis we place on leadership skills for our trainees and postdoctoral fellows, increasing number of students interested in toxicology and environmental health, substantial institutional commitment, strong and well-funded research programs of our faculty, and the excellence of the training environment.

NIH Research Projects · FY 2026 · 1977-07

ABSTRACT This application is a competitive renewal of our (year 45) Cardiovascular and Pulmonary Research (CVP) Training Program. The University of Arizona (UA) is a top 20 of Research I (R1) institutions and has a proven track record of mentoring, research and collaborations across departmental and institutional boundaries. The UA is the only R1 University with Hispanic Serving Institution and American Indian & Alaska Native-Serving (AIANSI) status with 20% of all graduate students from underrepresented populations (URPs). The UA has seen an unprecedented focus on heart, vascular and pulmonary research – bringing new, well-funded faculty, committed to mentorship, to this renewal application. Substantive improvements in infrastructure and new opportunities enable our trainees to gain true translational experiences. Two UA Colleges of Medicine - one in Tucson (UA-COM-T) and one in Phoenix (UA-COM-P) are committed to translational CVP research by building state-of-the art infrastructure through intra-institutional partnerships among key Research Centers. The CVP Program is organized into 3 strong, synergistic interdisciplinary research themes: 1) Molecular Basis of Cardiac Function and Disease, 2) Signaling in Vascular and Pulmonary Disease, and 3) Cardiovascular and Pulmonary Disease – Molecules to Treatments. This organization creates a robust pipeline of integrative basic and physician-scientist teams engaged in foundational physiological CVP research, with modern and relevant research proficiencies, with verbal and written communication, mentorship, collaborative and networking competencies. The CVP Program has evolved to meet the increased need for a diverse workforce and demand in health-related careers by delivering a contemporary didactic experience in physiological CVP research, applied research skills, and career development. All CVP Trainees benefit from state-of-the-art Core facilities, CVP disease-focused Research Centers, and unmatched Institutional resources to address the modern-era of data-driven research, including the “All of Us” Program, CyVerse and the Data Science Institute. The training plan aligns with the NIH mission of T32 translational research training where predoctoral, MD/PhD, clinical and postdoctoral trainees receive a broad background in biomedical and interdisciplinary research, multiple experimental approaches, and practical and ethical aspects of careers in science. Trainees also develop presentation and intrapersonal skills through journal clubs, MD/PhD colloquium, “meet the speaker” seminar program and attending institutional, national and international Cardiology and Pulmonary conferences. The postdoctoral training plan fosters a comprehensive path towards independence by expanding research focus, learning state-of-the-art techniques, and honing scientific writing skills. Formal courses with active-learning options are continuously revised (e.g., addition of courses on sex/gender differences and health disparities) and global training in building translational teams via the Eureka International Institute is available. >90% of trainees supported by this program remain in research-positions, a positive indicator of the success of our program.